Ignite Creation Date:
2025-12-24 @ 4:37 PM
Ignite Modification Date:
2026-01-21 @ 2:26 PM
Study NCT ID:
NCT02230566
Status:
COMPLETED
Last Update Posted:
2020-07-30
First Post:
2014-08-22
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Phase 3 Study of UX003 Recombinant Human Betaglucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016538', 'term': 'Mucopolysaccharidosis VII'}, {'id': 'D009083', 'term': 'Mucopolysaccharidoses'}, {'id': 'D035583', 'term': 'Rare Diseases'}, {'id': 'D016464', 'term': 'Lysosomal Storage Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}], 'ancestors': [{'id': 'D002239', 'term': 'Carbohydrate Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D017520', 'term': 'Mucinoses'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000654126', 'term': 'vestronidase alfa'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'kmooney@ultragenyx.com', 'phone': '408-981-3526', 'title': 'Kim Mooney, Associate Director, Patient Advocacy Medical Services', 'organization': 'Ultragenyx Pharmaceutical Inc'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Safety information was collected for all participants who received any study drug from signing the informed consent form through 30 days after last dose of study drug. Mean treatment duration for UX003 was 36.0 weeks, and for placebo was 15.8 weeks.', 'description': 'Treatment-emergent adverse events (TEAEs) are presented. Given that the study has only has 12 participants, and a by arm/group analysis would include no more than 3 participants per arm/group, the TEAE summary was planned to present data by treatment only.', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Participants received placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study, based on the blind-start design.', 'otherNumAtRisk': 9, 'otherNumAffected': 9, 'seriousNumAtRisk': 9, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'UX003 Active Treatment', 'description': 'Participants received 4 mg/kg UX003 QOW per group assignment (based on the blind-start design) and were dosed through Week 46. All groups received a minimum of 24 weeks of treatment with UX003.', 'otherNumAtRisk': 12, 'otherNumAffected': 12, 'seriousNumAtRisk': 12, 'seriousNumAffected': 2}], 'otherEvents': [{'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Skin papilloma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Anaphylactoid reaction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Seasonal allergy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Infusion site extravasation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Oedema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Catheter site bruise', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Chills', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Infusion site bruising', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Infusion site swelling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Peripheral swelling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Infusion site discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Post-traumatic stress disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Depression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Excoriation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Contusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Post-traumatic neck syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Tooth fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Fall', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Craniocerebral injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Body temperature increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Dyspnoea exertional', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Nasal obstruction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Productive cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Rhinorrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Ataxia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Clonus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Dysstasia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Eye pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Ear pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Abdominal pain lower', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Abnormal faeces', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Rectal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Cheilosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Urinary incontinence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 3}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Urticaria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Pruritus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Rash macular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Rash papular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Skin ulcer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 4}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Arthritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Joint range of motion decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Musculoskeletal stiffness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Joint swelling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Dehydration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 5}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Ear infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Cellulitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Conjunctivitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Gastrointestinal viral infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Oral herpes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Rash pustular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Otitis media acute', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}], 'seriousEvents': [{'term': 'Craniocerebral injury', 'notes': 'CTCAE grade 2 non-related craniocerebral injury as a result of falling off the bed. Computed tomography scan of the head did not show intracranial bleeding nor acute intracranial injury.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Anaphylactoid reaction', 'notes': 'CTCAE grade 3 treatment-related anaphylactoid reaction secondary to an infusion rate error occurring during the first hour of UX003 administration.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'European Union (EU) and Rest of World: Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate (DS) at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '-64.82', 'spread': '2.468', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '< 0.0001', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-64.82', 'ciLowerLimit': '-69.66', 'ciUpperLimit': '-59.98', 'pValueComment': 'P-values are from GEE model including baseline value, and the post UX003 Treatment Week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Baseline was defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect was subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Percent change from baseline in uGAG DS was analyzed by generalized estimating equation (GEE) modeling based on observed data. The GEE model included included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within subjects was assumed to be exchangeable.\n\nIn the United States (US), this was considered a secondary outcome measure. Per guidance from the Food and Drug Administration (FDA), no primary efficacy variable was declared in the US. Efficacy was to be based on the totality of the clinical data on a per participant basis.', 'unitOfMeasure': 'percentage change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Multi-Domain Responder Index (MDRI) Score at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.5', 'spread': '0.8', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.0527', 'groupIds': ['OG000'], 'statisticalMethod': 't-test', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'P value from t-test of "no change" (0 change) from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'MDRI score, calculated as the total response score at UX003 Treatment Week 24 across 6 domains: 6-Minute Walk Test, forced vital capacity predicted value, shoulder flexion, visual acuity, and Bruininks-Oseretsky Test of Motor Proficiency fine motor and gross motor capacity. For each domain, a minimally important difference (MID) was pre-specified. Changes from before treatment (baseline) to 24 weeks after treatment in each domain variable were scored against pre-specified MIDs. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) An improvement or decline ≥ MID was scored either as a +1 or -1, respectively, and a change \\<MID was scored as 0. The integration of benefit occurred by summing the responses (-1, +1, 0) across all 6 domain variables to derive the MDRI score, with a range of -6 (greatest possible decline) to +6 (greatest possible improvement).', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in 6-Minute Walk Test (6MWT) at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '20.8', 'spread': '16.75', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.2137', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '20.8', 'ciLowerLimit': '-12.0', 'ciUpperLimit': '53.7', 'pValueComment': 'P-values are from GEE model including baseline value, and the post UX003 Treatment Week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'The total distance walked (in meters) in a 6-minute period was measured. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) A positive change from Baseline indicates improvement. Change from baseline in 6MWT was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and at least one post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'unitOfMeasure': 'meters', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Pulmonary Function Testing: Percentage of Predicted Forced Vital Capacity (FVC%Pred) at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'spread': 'NA', 'comment': '1 participant evaluated', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Spirometry was administered to participants who did not require invasive ventilatory support or have a tracheostomy and measured percentage of predicted FVC. The percent predicted values were calculated after testing using published normative data. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) No GEE analysis was performed for FVC due to the limitation of the sample size.', 'unitOfMeasure': 'percentage predicted FVC', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Pulmonary Function Testing: Maximum Ventilatory Ventilation (MVV) at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Spirometry was administered to participants who did not require invasive ventilatory support or have a tracheostomy to measure MVV. The percent predicted values were calculated after testing using published normative data. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.)', 'reportingStatus': 'POSTED', 'populationDescription': 'No change from baseline was calculated and no GEE analysis was performed due to lack of data at baseline and/or UX003 Treatment Week 24.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Shoulder Flexion and Extension Maximum Range of Motion at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'title': 'Shoulder flexion - left', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-6.5', 'spread': '4.86', 'groupId': 'OG000'}]}]}, {'title': 'Shoulder extension - left', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-1.5', 'spread': '4.83', 'groupId': 'OG000'}]}]}, {'title': 'Shoulder flexion - right', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-1.8', 'spread': '3.54', 'groupId': 'OG000'}]}]}, {'title': 'Shoulder extension - right', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-3.4', 'spread': '3.48', 'groupId': 'OG000'}]}]}, {'title': 'Tighter shoulder flexion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-9.4', 'spread': '4.6', 'groupId': 'OG000'}]}]}, {'title': 'Tighter shoulder extension', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-6.7', 'spread': '3.53', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.1778', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-6.5', 'ciLowerLimit': '-16.1', 'ciUpperLimit': '3.0', 'groupDescription': 'Shoulder Flexion - Left', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.7632', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.5', 'ciLowerLimit': '-10.9', 'ciUpperLimit': '8.0', 'groupDescription': 'Shoulder Extension - Left', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.6034', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.8', 'ciLowerLimit': '-8.8', 'ciUpperLimit': '5.1', 'groupDescription': 'Shoulder Flexion - Right', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.3332', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-3.4', 'ciLowerLimit': '-10.2', 'ciUpperLimit': '3.4', 'groupDescription': 'Shoulder Extension - Right', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.0415', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-9.4', 'ciLowerLimit': '-18.4', 'ciUpperLimit': '-0.4', 'groupDescription': 'Tighter Shoulder Flexion', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.0563', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-6.7', 'ciLowerLimit': '-13.6', 'ciUpperLimit': '0.2', 'groupDescription': 'Tighter Shoulder Extension', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Goniometry was used to measure (in degrees) the maximum passive shoulder range of motion in both flexion and extension. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Change from baseline in shoulder flexion-left was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and at least one post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'unitOfMeasure': 'degrees', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Uncorrected Visual Acuity at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'title': 'Left eye', 'categories': [{'measurements': [{'value': '1', 'spread': '0.63', 'groupId': 'OG000'}]}]}, {'title': 'Right eye', 'categories': [{'measurements': [{'value': '0.9', 'spread': '0.51', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.1140', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.0', 'ciLowerLimit': '-0.2', 'ciUpperLimit': '2.2', 'groupDescription': 'for the left eye', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.0906', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.9', 'ciLowerLimit': '-0.1', 'ciUpperLimit': '1.8', 'groupDescription': 'for the right eye', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Visual acuity was measured (corrected and uncorrected) using a standard eye chart and recorded for each eye independently. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. The change in the number of lines from pre-treatment baseline to 24 weeks of treatment was evaluated. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) A positive change from baseline indicates improvement. Change from baseline in uncorrected visual acuity was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and at least one post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'unitOfMeasure': 'lines', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) Scores at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'title': 'Balance', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.8', 'spread': '0.46', 'groupId': 'OG000'}]}]}, {'title': 'Fine motor precision', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.23', 'groupId': 'OG000'}]}]}, {'title': 'Manual dexterity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.2', 'spread': '0.21', 'groupId': 'OG000'}]}]}, {'title': 'Running speed and agility', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.2', 'spread': '0.12', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.0883', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.8', 'ciLowerLimit': '-0.1', 'ciUpperLimit': '1.7', 'groupDescription': 'Scale-BALANCE', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.3528', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.2', 'ciLowerLimit': '-0.7', 'ciUpperLimit': '0.2', 'groupDescription': 'Scale: FINE MOTOR PRECISION', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.4094', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.2', 'ciLowerLimit': '-0.2', 'ciUpperLimit': '0.6', 'groupDescription': 'Scale-MANUAL DEXTERITY', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.1020', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.2', 'ciLowerLimit': '0.0', 'ciUpperLimit': '0.4', 'groupDescription': 'Scale-RUNNING SPEED AND AGILITY', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'BOT-2 was administered to evaluate treatment-related changes in 4 domains assessing both fine and gross motor function: balance (score 0 to 37), fine motor precision (score 0 to 41), manual dexterity (score 0 to 45), and running speed/agility (score 0 to 52). Higher scores indicate more motor proficiency; a positive change from baseline indicates improvement. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Change from baseline in BOT-2 was analyzed by GEE modeling based on observed data. The GEE model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '3.4', 'spread': '2.64', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.1953', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '3.4', 'ciLowerLimit': '-1.8', 'ciUpperLimit': '8.6', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'The PedsQL 18-item scale is comprised of 3 dimensions: general fatigue (6 items), sleep/rest fatigue (6 items) and cognitive fatigue (6 items). Each item has a 5-point Likert response scale that is reverse scored and transformed to a 0 to 100 scale with higher scores indicating less fatigue. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Change from baseline in PedsQL total fatigue score was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and ≥1 post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Percentage of Individual Clinical Response (ICR) Responders at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '25', 'groupId': 'OG000', 'lowerLimit': '8.3', 'upperLimit': '53.8'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': "Percentage of participants who were ICR responders based on MID criteria at Week 24. At the Randomization visit, the physician queried the participant or parent/caregiver about signs and symptoms of MPS VII that interfered most with the participant's daily life. Answers were mapped to an appropriate clinical outcome measure (e.g., difficulty walking could map to the 6MWT; breathing problems to FVC). The clinical outcome ranked with the highest impact on daily life that could be reliably completed by the participant and met a threshold level of impairment was selected as the ICR for that participant. ICR response was assessed based on a positive change (according to pre-specified MID criteria) of each participant's ICR. Agresti-Coull confidence interval with nominal coverage ≥ 95%.", 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Impactful Clinical Problem Total Score at UX003 Treatment Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'UX003 4 mg/kg', 'description': 'Participants were randomized 1:1:1:1 to 1 of 4 treatment sequence groups to either start treatment with 4 mg/kg UX003 (Group A), or placebo for the first 8 weeks (Group B), 16 weeks (Group C) or 24 weeks (Group D) of the study and cross over to 4 mg/kg UX003. Participants were dosed QOW through Week 46. All groups received a minimum of 24 weeks of treatment with 4 mg/kg UX003 QOW.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.2', 'spread': '0.92', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.2022', 'groupIds': ['OG000'], 'paramType': 'LS Mean', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.2', 'ciLowerLimit': '-3.0', 'ciUpperLimit': '0.6', 'statisticalMethod': 'GEE', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'The 3 most impactful clinical problems as reported by the subject/parent/caregiver during the Clinical Problem Evaluation were scored on a Likert scale from 1 (very little problem) to 7 (an extreme amount) at randomization and post-randomization visits. At post-randomization visits, each clinical problem was again scored for impact on daily activities. Total scores ranged from 3 to 21; lower scores reflect less impact on daily life. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) The change from baseline up to UX003 Treatment Week 24 were analyzed by GEE modeling, including baseline value, and the post-UX003 initiation treatment week as a categorical variable. The covariance structure within participants is assumed to be exchangeable.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who had non-missing baseline and ≥1 post-baseline value during 24 weeks of UX003 treatment. Given a randomized blind start and single crossover study design, all 4 groups received a minimum of 24 weeks of UX003 treatment, with a placebo treatment period ranging from 0-24 weeks, by group. Analysis of placebo data was not planned.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Group A: 4 mg/kg UX003', 'description': '4 mg/kg UX003 every other week (QOW) through Week 46'}, {'id': 'FG001', 'title': 'Group B: 8 Weeks Placebo Then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46'}, {'id': 'FG002', 'title': 'Group C: 16 Weeks Placebo Then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46'}, {'id': 'FG003', 'title': 'Group D: 24 Weeks Placebo Then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '3'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '3'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '12', 'groupId': 'BG004'}]}], 'groups': [{'id': 'BG000', 'title': 'Group A: 4 mg/kg UX003', 'description': '4 mg/kg UX003 QOW through Week 46'}, {'id': 'BG001', 'title': 'Group B: 8 Weeks Placebo Then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46'}, {'id': 'BG002', 'title': 'Group C: 16 Weeks Placebo Then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46'}, {'id': 'BG003', 'title': 'Group D: 24 Weeks Placebo Then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46'}, {'id': 'BG004', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '13.13', 'spread': '1.656', 'groupId': 'BG000'}, {'value': '12.50', 'spread': '4.004', 'groupId': 'BG001'}, {'value': '20.77', 'spread': '3.004', 'groupId': 'BG002'}, {'value': '15.23', 'spread': '8.633', 'groupId': 'BG003'}, {'value': '15.41', 'spread': '5.492', 'groupId': 'BG004'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '8', 'groupId': 'BG004'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '4', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 12}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-12'}, 'expandedAccessInfo': {'nctId': 'NCT03775174', 'statusForNctId': 'AVAILABLE', 'hasExpandedAccess': True}, 'statusVerifiedDate': '2020-07', 'dispFirstSubmitDate': '2017-05-08', 'completionDateStruct': {'date': '2016-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-07-16', 'studyFirstSubmitDate': '2014-08-22', 'dispFirstSubmitQcDate': '2017-05-08', 'resultsFirstSubmitDate': '2017-11-29', 'studyFirstSubmitQcDate': '2014-08-28', 'dispFirstPostDateStruct': {'date': '2017-05-10', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2020-07-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-01-22', 'studyFirstPostDateStruct': {'date': '2014-09-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-02-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'European Union (EU) and Rest of World: Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate (DS) at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Baseline was defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect was subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Percent change from baseline in uGAG DS was analyzed by generalized estimating equation (GEE) modeling based on observed data. The GEE model included included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within subjects was assumed to be exchangeable.\n\nIn the United States (US), this was considered a secondary outcome measure. Per guidance from the Food and Drug Administration (FDA), no primary efficacy variable was declared in the US. Efficacy was to be based on the totality of the clinical data on a per participant basis.'}], 'secondaryOutcomes': [{'measure': 'Multi-Domain Responder Index (MDRI) Score at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'MDRI score, calculated as the total response score at UX003 Treatment Week 24 across 6 domains: 6-Minute Walk Test, forced vital capacity predicted value, shoulder flexion, visual acuity, and Bruininks-Oseretsky Test of Motor Proficiency fine motor and gross motor capacity. For each domain, a minimally important difference (MID) was pre-specified. Changes from before treatment (baseline) to 24 weeks after treatment in each domain variable were scored against pre-specified MIDs. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) An improvement or decline ≥ MID was scored either as a +1 or -1, respectively, and a change \\<MID was scored as 0. The integration of benefit occurred by summing the responses (-1, +1, 0) across all 6 domain variables to derive the MDRI score, with a range of -6 (greatest possible decline) to +6 (greatest possible improvement).'}, {'measure': 'Change From Baseline in 6-Minute Walk Test (6MWT) at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'The total distance walked (in meters) in a 6-minute period was measured. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) A positive change from Baseline indicates improvement. Change from baseline in 6MWT was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and at least one post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.'}, {'measure': 'Change From Baseline in Pulmonary Function Testing: Percentage of Predicted Forced Vital Capacity (FVC%Pred) at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Spirometry was administered to participants who did not require invasive ventilatory support or have a tracheostomy and measured percentage of predicted FVC. The percent predicted values were calculated after testing using published normative data. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) No GEE analysis was performed for FVC due to the limitation of the sample size.'}, {'measure': 'Change From Baseline in Pulmonary Function Testing: Maximum Ventilatory Ventilation (MVV) at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Spirometry was administered to participants who did not require invasive ventilatory support or have a tracheostomy to measure MVV. The percent predicted values were calculated after testing using published normative data. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.)'}, {'measure': 'Change From Baseline in Shoulder Flexion and Extension Maximum Range of Motion at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Goniometry was used to measure (in degrees) the maximum passive shoulder range of motion in both flexion and extension. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Change from baseline in shoulder flexion-left was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and at least one post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.'}, {'measure': 'Change From Baseline in Uncorrected Visual Acuity at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'Visual acuity was measured (corrected and uncorrected) using a standard eye chart and recorded for each eye independently. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. The change in the number of lines from pre-treatment baseline to 24 weeks of treatment was evaluated. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) A positive change from baseline indicates improvement. Change from baseline in uncorrected visual acuity was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and at least one post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.'}, {'measure': 'Change From Baseline in Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) Scores at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'BOT-2 was administered to evaluate treatment-related changes in 4 domains assessing both fine and gross motor function: balance (score 0 to 37), fine motor precision (score 0 to 41), manual dexterity (score 0 to 45), and running speed/agility (score 0 to 52). Higher scores indicate more motor proficiency; a positive change from baseline indicates improvement. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Change from baseline in BOT-2 was analyzed by GEE modeling based on observed data. The GEE model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.'}, {'measure': 'Change From Baseline in Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'The PedsQL 18-item scale is comprised of 3 dimensions: general fatigue (6 items), sleep/rest fatigue (6 items) and cognitive fatigue (6 items). Each item has a 5-point Likert response scale that is reverse scored and transformed to a 0 to 100 scale with higher scores indicating less fatigue. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Change from baseline in PedsQL total fatigue score was analyzed by GEE modeling based on observed data. The GEE model included all participants who had non-missing baseline and ≥1 post-baseline value during the 24 weeks of UX003 treatment. The model included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within participants was assumed to be exchangeable.'}, {'measure': 'Percentage of Individual Clinical Response (ICR) Responders at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': "Percentage of participants who were ICR responders based on MID criteria at Week 24. At the Randomization visit, the physician queried the participant or parent/caregiver about signs and symptoms of MPS VII that interfered most with the participant's daily life. Answers were mapped to an appropriate clinical outcome measure (e.g., difficulty walking could map to the 6MWT; breathing problems to FVC). The clinical outcome ranked with the highest impact on daily life that could be reliably completed by the participant and met a threshold level of impairment was selected as the ICR for that participant. ICR response was assessed based on a positive change (according to pre-specified MID criteria) of each participant's ICR. Agresti-Coull confidence interval with nominal coverage ≥ 95%."}, {'measure': 'Change From Baseline in Impactful Clinical Problem Total Score at UX003 Treatment Week 24', 'timeFrame': 'Baseline (defined as the last assessment prior to or on the date of cross-over to active treatment with UX003) to 24 weeks of UX003 study drug treatment', 'description': 'The 3 most impactful clinical problems as reported by the subject/parent/caregiver during the Clinical Problem Evaluation were scored on a Likert scale from 1 (very little problem) to 7 (an extreme amount) at randomization and post-randomization visits. At post-randomization visits, each clinical problem was again scored for impact on daily activities. Total scores ranged from 3 to 21; lower scores reflect less impact on daily life. Baseline was defined as the last assessment prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect would be subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) The change from baseline up to UX003 Treatment Week 24 were analyzed by GEE modeling, including baseline value, and the post-UX003 initiation treatment week as a categorical variable. The covariance structure within participants is assumed to be exchangeable.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['MPS 7', 'Sly Syndrome', 'Mucopolysaccharidosis', 'MPS VII', 'Enzyme Replacement Therapy', 'Mucopolysaccharidosis type 7', 'rare disease', 'lysosomal storage disease', 'metabolic disorder'], 'conditions': ['MPS 7', 'Sly Syndrome', 'Mucopolysaccharidosis', 'MPS VII']}, 'referencesModule': {'references': [{'pmid': '32063397', 'type': 'RESULT', 'citation': 'Wang RY, da Silva Franco JF, Lopez-Valdez J, Martins E, Sutton VR, Whitley CB, Zhang L, Cimms T, Marsden D, Jurecka A, Harmatz P. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII. Mol Genet Metab. 2020 Mar;129(3):219-227. doi: 10.1016/j.ymgme.2020.01.003. Epub 2020 Jan 11.'}, {'pmid': '29478819', 'type': 'RESULT', 'citation': 'Harmatz P, Whitley CB, Wang RY, Bauer M, Song W, Haller C, Kakkis E. A novel Blind Start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease. Mol Genet Metab. 2018 Apr;123(4):488-494. doi: 10.1016/j.ymgme.2018.02.006. Epub 2018 Feb 12.'}, {'pmid': '37415957', 'type': 'DERIVED', 'citation': 'Montano AM, Rozdzynska-Swiatkowska A, Jurecka A, Ramirez AN, Zhang L, Marsden D, Wang RY, Harmatz P. Growth patterns in patients with mucopolysaccharidosis VII. Mol Genet Metab Rep. 2023 Jun 26;36:100987. doi: 10.1016/j.ymgmr.2023.100987. eCollection 2023 Sep.'}, {'pmid': '33874971', 'type': 'DERIVED', 'citation': 'Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.'}, {'pmid': '30467742', 'type': 'DERIVED', 'citation': 'Qi Y, McKeever K, Taylor J, Haller C, Song W, Jones SA, Shi J. Pharmacokinetic and Pharmacodynamic Modeling to Optimize the Dose of Vestronidase Alfa, an Enzyme Replacement Therapy for Treatment of Patients with Mucopolysaccharidosis Type VII: Results from Three Trials. Clin Pharmacokinet. 2019 May;58(5):673-683. doi: 10.1007/s40262-018-0721-y.'}]}, 'descriptionModule': {'briefSummary': 'The Phase 3 study will use a novel randomized, intra-subject placebo-controlled, single crossover design, referred to as Blind Start, to evaluate the safety and efficacy of UX003. The Blind Start is a novel design whereby participants will be randomized to 1 of 4 groups, each representing a different treatment sequence, and will cross over to UX003 at different pre-defined time points in a blinded manner. All groups will receive a minimum of 24 weeks treatment with 4 mg/kg UX003 every other week (QOW).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '35 Years', 'minimumAge': '5 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing.\n* Elevated urinary glycosaminoglycan (uGAG) excretion at a minimum of 3-fold over the mean normal for age (at Screening).\n* Apparent clinical signs of lysosomal storage disease as judged by the Investigator, including at least one of the following: enlarged liver and spleen, joint limitations, airway obstruction or pulmonary problems, limitation of mobility while still ambulatory.\n* Aged 5 - 35 years, inclusive.\n* Willing and able to provide written informed consent, or in the case of subjects under the age of 18 (or 16 years, depending on the region), provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.\n* Sexually active subjects must be willing to use acceptable highly effective methods of contraception while participating in the study and for 30 days following the last dose.\n* Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not experienced menarche, or have had tubal ligation at least one year prior to Screening, or who have had total hysterectomy.\n* Naïve to treatment with UX003.\n\nExclusion Criteria:\n\n* Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells.\n* Major surgery within 3 months prior to study entry or planned major surgery during the study that may not allow safe participation in the study.\n* Presence or history of any hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.\n* Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.\n* Use of any investigational product (drug or device or combination) within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.\n* Presence of a condition of such severity and acuity that, in the opinion of the Investigator, warrants immediate surgical intervention or other treatment or may not allow safe participation in the study.\n* Concurrent disease or condition, or laboratory abnormality that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduce additional safety concerns.'}, 'identificationModule': {'nctId': 'NCT02230566', 'briefTitle': 'A Phase 3 Study of UX003 Recombinant Human Betaglucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Ultragenyx Pharmaceutical Inc'}, 'officialTitle': 'A Randomized, Placebo-Controlled, Blind-Start, Single-Crossover Phase 3 Study to Assess the Efficacy and Safety of UX003 rhGUS Enzyme Replacement Therapy in Patients With MPS 7', 'orgStudyIdInfo': {'id': 'UX003-CL301'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group A: 4 mg/kg UX003', 'description': '4 mg/kg UX003 QOW through Week 46', 'interventionNames': ['Drug: UX003']}, {'type': 'EXPERIMENTAL', 'label': 'Group B: 8 Weeks Placebo then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46', 'interventionNames': ['Drug: UX003', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Group C: 16 Weeks Placebo then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46', 'interventionNames': ['Drug: UX003', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Group D: 24 Weeks Placebo then 4 mg/kg UX003', 'description': 'Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46', 'interventionNames': ['Drug: UX003', 'Other: Placebo']}], 'interventions': [{'name': 'UX003', 'type': 'DRUG', 'otherNames': ['recombinant human beta-glucuronidase', 'rh-β-glucuronidase', 'rhGUS'], 'description': 'UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion', 'armGroupLabels': ['Group A: 4 mg/kg UX003', 'Group B: 8 Weeks Placebo then 4 mg/kg UX003', 'Group C: 16 Weeks Placebo then 4 mg/kg UX003', 'Group D: 24 Weeks Placebo then 4 mg/kg UX003']}, {'name': 'Placebo', 'type': 'OTHER', 'otherNames': ['Reference therapy'], 'description': 'Placebo consisting of the UX003 formulation buffer (without rhGUS)', 'armGroupLabels': ['Group B: 8 Weeks Placebo then 4 mg/kg UX003', 'Group C: 16 Weeks Placebo then 4 mg/kg UX003', 'Group D: 24 Weeks Placebo then 4 mg/kg UX003']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94609', 'city': 'Oakland', 'state': 'California', 'country': 'United States', 'facility': "Children's Hospital Oakland", 'geoPoint': {'lat': 37.80437, 'lon': -122.2708}}, {'zip': '92868', 'city': 'Orange', 'state': 'California', 'country': 'United States', 'facility': "Children's Hospital of Orange County", 'geoPoint': {'lat': 33.78779, 'lon': -117.85311}}, {'zip': '33155', 'city': 'Miami', 'state': 'Florida', 'country': 'United States', 'facility': "Miami Children's Hospital", 'geoPoint': {'lat': 25.77427, 'lon': -80.19366}}, {'zip': '55455', 'city': 'Minneapolis', 'state': 'Minnesota', 'country': 'United States', 'facility': 'University of Minnesota', 'geoPoint': {'lat': 44.97997, 'lon': -93.26384}}], 'overallOfficials': [{'name': 'Paul Harmatz, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "UCSF Benioff Children's Hospital Oakland"}, {'name': 'Raymond Wang, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Children's Hospital of Orange County"}, {'name': 'Mislen Bauer, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Nicklaus Children's Hospital f/k/a Miami Children's Hospital"}, {'name': 'Chester Whitley, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Minnesota'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ultragenyx Pharmaceutical Inc', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}