Ignite Creation Date:
2025-12-24 @ 9:41 PM
Ignite Modification Date:
2025-12-29 @ 9:01 PM
Study NCT ID:
NCT05025332
Status:
COMPLETED
Last Update Posted:
2025-06-18
First Post:
2021-08-24
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2025-03-25', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'C537403', 'term': 'Pitt-Hopkins syndrome'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C540261', 'term': 'cyclo-L-glycyl-L-2-allylproline'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'MedicalInformation@neurenpharma.com', 'phone': '+61 (3) 9092 0480', 'title': 'Chief Medical Officer', 'organization': 'Neuren Pharmaceuticals'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '15 weeks for each participant starting on the day of first dosing', 'eventGroups': [{'id': 'EG000', 'title': 'NNZ-2591', 'description': 'All enrolled participants who received at least one dose of IMP', 'otherNumAtRisk': 16, 'deathsNumAtRisk': 16, 'otherNumAffected': 15, 'seriousNumAtRisk': 16, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Irritability', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Contusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Gastroenteritis - viral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Rhinorrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Covid-10', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Ear Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Escherichia urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Influenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Otitis Media', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Pharyngitis streptococcal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Abdominal Distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Abdominal Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Breath Odour', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Faeces Hard', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Tongue Dry', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Arthropod Bite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Fall', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Lethargy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Intentional Self Injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Middle Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Sleep Disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Productive Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Refraction Disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Decreased Appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Pyelocaliectasis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 16, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 24.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Safety and Tolerability', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'NNZ-2591', 'description': 'All enrolled participants'}], 'classes': [{'title': 'Participants with TEAE', 'categories': [{'measurements': [{'value': '15', 'groupId': 'OG000'}]}]}, {'title': 'Participants with Serious TEAE', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Participants who discontinued due to TEAE', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}, {'title': 'Participants with mild TEAE as highest intensity', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}]}]}, {'title': 'Participants with moderate TEAE as highest intensity', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': 'Participants with severe TEAE as highest intensity', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '13 weeks', 'description': 'To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population - all participants receiving at least one dose of NNZ-2591'}, {'type': 'PRIMARY', 'title': 'Pharmacokinetic - Mean AUC24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'NNZ-2591', 'description': 'PK population:\n\nAll participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who undergo PK sample collection at least one of the specified post-dose time point(s).'}], 'classes': [{'categories': [{'measurements': [{'value': '305', 'spread': '56.1', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.', 'description': 'Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.', 'unitOfMeasure': 'ug.h/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who underwent PK sample collection at least one of the specified post-dose time point(s).'}, {'type': 'PRIMARY', 'title': 'Pharmacokinetic - t1/2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'NNZ-2591', 'description': 'PK population:\n\nAll participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who undergo PK sample collection at least one of the specified post-dose time point(s).'}], 'classes': [{'categories': [{'measurements': [{'value': '7.17', 'spread': '1.64', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.', 'description': 'Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.', 'unitOfMeasure': 'hours', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who undergo PK sample collection at least one of the specified post-dose time point(s).'}, {'type': 'SECONDARY', 'title': 'Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.6', 'spread': '0.92', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '.0039', 'groupIds': ['OG000'], 'groupDescription': 'Descriptive statistics were used to summarize the data. For total scores, waterfall plots and histograms/bar charts were created at the EOT visit with plots for all participants.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'null median = 4, not 0'}], 'paramType': 'MEAN', 'timeFrame': 'CGI-I was assessed at weeks 6, 13/EOT & 15. Overall improvement scores relate to week 13/EOT visit.', 'description': 'Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement. Score on a Likert scale (1-7) where lower scores are better.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified intention to treat (MITT)'}, {'type': 'SECONDARY', 'title': 'Caregiver Impression of Improvement: Overall Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '3.0', 'spread': '1.00', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.0234', 'groupIds': ['OG000'], 'groupDescription': 'Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participants.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'null median = 4, not 0'}], 'paramType': 'MEAN', 'timeFrame': 'CIC was assessed at Week13/EOT', 'description': 'Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.5', 'spread': '0.52', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.0313', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).', 'description': 'Pitt Hopkins syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Change from baselines on overall Score based on a 7 point Likert scale (1-7) where lower scores are better.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified intention to treat (MITT) population'}, {'type': 'SECONDARY', 'title': 'Caregiver Top 3 Concerns', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.606', 'spread': '1.5385', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.0039', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.', 'description': 'Caregiver Top 3 Concerns: Change from baseline in Average Concern Severity. The average concern severity defined as the average of the severity scores for the three concerns evaluated at a given visit, and was calculated as long as at least one concern was useable for analysis at the visit. Scores range from 0 - 10 with higher scores indicating greater concern severity. A negative change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified intention to treat population'}, {'type': 'SECONDARY', 'title': 'MacArthur-Bates Communicative Development Inventory (MB-CDI)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '15.9', 'spread': '42.07', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.1934', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).', 'description': 'MacArthur-Bates Communicative Development Inventory (MB-CDI): Words Understood Domain. Scores ranges from 0-396, with higher scores indicating greater language ability. A positive change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Observer-Reported Communication Ability (ORCA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.97', 'spread': '8.963', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.7480', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score.', 'description': "Observer-Reported Communication Ability (ORCA): Change from baseline in Modified t-score. The ORCA measures an individual's communication abilities based on observations made by caregivers, parents, or other relevant observers, and is based on 4 domains: Expressive Communication, Receptive Communication, Social Communication, and Pragmatic Language Skills.\n\nScores range from 25.8 - 83.8, with higher scores indicating greater communication ability. A positive change from baseline indicates improvement. A T-score standardizes the individual's performance relative to a normative sample. It typically has a mean of 50 and a standard deviation of 10.\n\nT score = 50 + 10 × (X-µ)/σ Where: X is the individual's raw score μ is the population mean σ is the standard deviation", 'unitOfMeasure': 'T-score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Aberrant Behavior Checklist-2 (ABC-2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '-4.8', 'spread': '14.15', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.3203', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.', 'description': 'Aberrant Behavior Checklist-2 (ABC-2): Change from baseline in Total Score. Range of scores is 0-174, with higher scores indicating more behavioral issues. A negative change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'CSHQ', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.4', 'spread': '1.79', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.3574', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.', 'description': 'Child Sleep Habits Questionnaire (CSHQ). Total Score. Change from baseline. Range of scores was (33-99) with higher scores being worse.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'GIHQ', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '-6.3', 'spread': '21.83', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.4131', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.', 'description': 'Gastrointestinal Health Questionnaire (GIHQ). Change from baseline in total frequency score. Range of scores was (0-197) with higher scores being worse.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Vineland Adaptive Behavior Scales-3, Interview Version', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.0', 'spread': '2.36', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.9063', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score.', 'description': 'Vineland Adaptive Behavior Scales-3 (VABS-3), Interview version, Change from baseline in Adaptive Behavior Composite Standard Score. Scores range from 20 - 140 with higher scores indicating greater functional abilities. A positive change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'one participant completed baseline VABS-3 but did not complete VABS-3 at EOT visit. Hence number analysed is only 10.'}, {'type': 'SECONDARY', 'title': 'Modified Two-minute Walk Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '8.704', 'spread': '25.7178', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in distance travelled on two minute walk test.', 'description': 'Modified two-minute walk test. Change from baseline in distance travelled (m) on 2 minute walk test. The test was only administered for participants who were ambulatory and able to complete the assessment. A positive score on change from baseline indicates improvement in distance walked.', 'unitOfMeasure': 'meters', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'QI-Disability', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.672', 'spread': '9.8493', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.7002', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.', 'description': 'Quality of Life Inventory-Disability (QI-Disability). Overall Score change from baseline. Scores range from 0 - 100 with higher scores indicating better quality of life. A positive change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'ICND', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.5', 'spread': '1.44', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.3750', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Change from baseline'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score.', 'description': 'Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating, change from baseline. Score ranges from 1 - 6, with a higher score indicating better quality of life. A positive change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Behavior Problems Inventory - Short Form', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '3.2', 'spread': '15.45', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.7695', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score.', 'description': 'Change from baseline in Behavior Problems Inventory - Short Form Total Frequency Score. Scores range from 0-120, with higher scores indicating greater frequency in behavior problems. A negative change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Modified Intention to Treat', 'description': 'All participants in the ITT population who completed treatment and completed the EOT visit.\n\nITT populations consists of all participants deemed eligible and enrolled into the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.444', 'spread': '2.4685', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.2402', 'groupIds': ['OG000'], 'groupDescription': 'Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.', 'statisticalMethod': 'Wilcoxon Signed rank', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.', 'description': 'Change from baseline in Non Verbal Development Quotient (NVDQ). Scores range from 40 - 160, with higher scores indicating greater development. A positive change from baseline indicates improvement.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Standard domain scores only calculated for participants 42 months of age and younger.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'NNZ-2591', 'description': 'All participants consenting'}], 'periods': [{'title': 'Screening', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '28'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}]}], 'dropWithdraws': [{'type': 'Screen failure', 'reasons': [{'groupId': 'FG000', 'numSubjects': '12'}]}]}, {'title': 'Treatment & Follow Up', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}]}]}], 'recruitmentDetails': 'Participants were recruited based on physician referral at 5 academic medical centers between August 2022 and December 2023', 'preAssignmentDetails': 'Following completion of informed consent, participants (28) underwent 4 weeks of baselining/screening. During this process 12 participants failed screening. The remaining 16 participants commenced treatment.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'NNZ-2591', 'description': 'All participants who successfully completed 4 week post consent screening period.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'title': '<=18 years', 'measurements': [{'value': '16', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '9.1', 'spread': '4.63', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '15', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'American Indian or Alaska Native', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Asian', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}]}]}, {'title': 'Black or African American', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Native Hawaiian or other Pacific Islander', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'White', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}]}]}, {'title': 'Other', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Multiple', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Unknown', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Clinical Global Impression of Severity (CGI-S)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '5.0', 'spread': '0.69', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Height (cm)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '127.26', 'spread': '22.609', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'centimetres', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Weight (kg)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '28.57', 'spread': '12.291', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kilograms', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Body Mass Index (kg/m^2)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '16.846', 'spread': '2.0979', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m^2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'PTHS variant', 'classes': [{'title': 'Substitution', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}, {'title': 'Deletion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}, {'title': 'Duplication', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Insertion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Inversion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Conversion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Deletion-Insertion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Complex', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Missense variant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': 'Nonsense variant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}]}]}, {'title': 'Frameshift variant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': 'Unknown', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Other', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'History of Developmental Regression', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Yes', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'No', 'measurements': [{'value': '15', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Autism Mental Status Exam', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '9.96', 'spread': '2.29', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'The AMSE is an observational assessment that looks at 8 items of social, communicative and behavioral functioning in individuals with Autism Spectrum Disorder, with each item yielding a potential score of 0, 1 or 2, with range of 0-16. Higher scores indicate greater levels of impairment.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Presence of Co-morbid Psychiatric Disorders', 'classes': [{'title': 'Autism Spectrum Disorder', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}, {'title': 'BiPolar Disorder', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Attention Deficit Disorder', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Obsessive Compulsive Disorder', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Other', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'BSID-4 NVDQ', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '11.602', 'spread': '7.3599', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': "Bayley Scales of Infant Development-4 (BSID-4) is used to measure the developmental functioning of children aged 1 to 42 months.\n\nThe Non-Verbal Developmental Quotient (NVDQ) is derived from the Cognitive scale of the BSID-4 and focuses on tasks that require no verbal responses.\n\nEach non-verbal task is scored and the raw scores are summed up and converted to a quotient comparing the child's developmental age to their chronological age This standardization allows comparison across children of different ages.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Participants who could not be assessed on the Stanford-Binet Intelligence (SB-5) due to their developmental level were assessed using the Bayley Scales of Infant Development instead.'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2023-10-30', 'size': 10718697, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_002.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2025-03-05T21:06', 'hasProtocol': True}, {'date': '2024-04-30', 'size': 1379968, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_003.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2025-03-05T21:13', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 28}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-10-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2024-05-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-06-01', 'studyFirstSubmitDate': '2021-08-24', 'resultsFirstSubmitDate': '2025-01-08', 'studyFirstSubmitQcDate': '2021-08-24', 'lastUpdatePostDateStruct': {'date': '2025-06-18', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-05-04', 'studyFirstPostDateStruct': {'date': '2021-08-27', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-05-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-02-27', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and Tolerability', 'timeFrame': '13 weeks', 'description': 'To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.'}, {'measure': 'Pharmacokinetic - Mean AUC24', 'timeFrame': 'Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.', 'description': 'Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.'}, {'measure': 'Pharmacokinetic - t1/2', 'timeFrame': 'Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.', 'description': 'Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.'}], 'secondaryOutcomes': [{'measure': 'Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement', 'timeFrame': 'CGI-I was assessed at weeks 6, 13/EOT & 15. Overall improvement scores relate to week 13/EOT visit.', 'description': 'Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement. Score on a Likert scale (1-7) where lower scores are better.'}, {'measure': 'Caregiver Impression of Improvement: Overall Score', 'timeFrame': 'CIC was assessed at Week13/EOT', 'description': 'Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better.'}, {'measure': 'Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score', 'timeFrame': 'Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).', 'description': 'Pitt Hopkins syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Change from baselines on overall Score based on a 7 point Likert scale (1-7) where lower scores are better.'}, {'measure': 'Caregiver Top 3 Concerns', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.', 'description': 'Caregiver Top 3 Concerns: Change from baseline in Average Concern Severity. The average concern severity defined as the average of the severity scores for the three concerns evaluated at a given visit, and was calculated as long as at least one concern was useable for analysis at the visit. Scores range from 0 - 10 with higher scores indicating greater concern severity. A negative change from baseline indicates improvement.'}, {'measure': 'MacArthur-Bates Communicative Development Inventory (MB-CDI)', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).', 'description': 'MacArthur-Bates Communicative Development Inventory (MB-CDI): Words Understood Domain. Scores ranges from 0-396, with higher scores indicating greater language ability. A positive change from baseline indicates improvement.'}, {'measure': 'Observer-Reported Communication Ability (ORCA)', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score.', 'description': "Observer-Reported Communication Ability (ORCA): Change from baseline in Modified t-score. The ORCA measures an individual's communication abilities based on observations made by caregivers, parents, or other relevant observers, and is based on 4 domains: Expressive Communication, Receptive Communication, Social Communication, and Pragmatic Language Skills.\n\nScores range from 25.8 - 83.8, with higher scores indicating greater communication ability. A positive change from baseline indicates improvement. A T-score standardizes the individual's performance relative to a normative sample. It typically has a mean of 50 and a standard deviation of 10.\n\nT score = 50 + 10 × (X-µ)/σ Where: X is the individual's raw score μ is the population mean σ is the standard deviation"}, {'measure': 'Aberrant Behavior Checklist-2 (ABC-2)', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.', 'description': 'Aberrant Behavior Checklist-2 (ABC-2): Change from baseline in Total Score. Range of scores is 0-174, with higher scores indicating more behavioral issues. A negative change from baseline indicates improvement.'}, {'measure': 'CSHQ', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.', 'description': 'Child Sleep Habits Questionnaire (CSHQ). Total Score. Change from baseline. Range of scores was (33-99) with higher scores being worse.'}, {'measure': 'GIHQ', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.', 'description': 'Gastrointestinal Health Questionnaire (GIHQ). Change from baseline in total frequency score. Range of scores was (0-197) with higher scores being worse.'}, {'measure': 'Vineland Adaptive Behavior Scales-3, Interview Version', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score.', 'description': 'Vineland Adaptive Behavior Scales-3 (VABS-3), Interview version, Change from baseline in Adaptive Behavior Composite Standard Score. Scores range from 20 - 140 with higher scores indicating greater functional abilities. A positive change from baseline indicates improvement.'}, {'measure': 'Modified Two-minute Walk Test', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in distance travelled on two minute walk test.', 'description': 'Modified two-minute walk test. Change from baseline in distance travelled (m) on 2 minute walk test. The test was only administered for participants who were ambulatory and able to complete the assessment. A positive score on change from baseline indicates improvement in distance walked.'}, {'measure': 'QI-Disability', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.', 'description': 'Quality of Life Inventory-Disability (QI-Disability). Overall Score change from baseline. Scores range from 0 - 100 with higher scores indicating better quality of life. A positive change from baseline indicates improvement.'}, {'measure': 'ICND', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score.', 'description': 'Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating, change from baseline. Score ranges from 1 - 6, with a higher score indicating better quality of life. A positive change from baseline indicates improvement.'}, {'measure': 'Behavior Problems Inventory - Short Form', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score.', 'description': 'Change from baseline in Behavior Problems Inventory - Short Form Total Frequency Score. Scores range from 0-120, with higher scores indicating greater frequency in behavior problems. A negative change from baseline indicates improvement.'}, {'measure': 'Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ)', 'timeFrame': 'Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.', 'description': 'Change from baseline in Non Verbal Development Quotient (NVDQ). Scores range from 40 - 160, with higher scores indicating greater development. A positive change from baseline indicates improvement.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Pitt Hopkins Syndrome'], 'conditions': ['Pitt Hopkins Syndrome']}, 'descriptionModule': {'briefSummary': 'A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome.', 'detailedDescription': 'The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetics of treatment with NNZ-2591 oral solution in children and adolescents with Pitt Hopkins Syndrome. The secondary purpose is to investigate measures of efficacy. Subjects will receive treatment with NNZ-2591 oral solution (50 mg/mL) doses for a total of 13 weeks.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Clinical diagnosis of PTHS with a documented disease-causing genetic etiology for the disorder.\n2. Males or females aged 3-17 years.\n3. Body weight of 12kg or higher at screening\n4. Subjects with a Clinical Global Impression- Severity (CGI-S) score of 4 or greater at the Screening visit.\n5. Not actively undergoing regression or loss of skills, defined as no persistent loss of previously acquired developmental skills for a period within 3 months of the Screening visit\n6. Each subject must be able to swallow the study medication provided as a liquid solution.\n7. Caregiver(s) must have sufficient English language skills.\n\nExclusion Criteria:\n\n1. Body weight \\<12kg at screening\n2. Clinically significant abnormalities in safety laboratory tests and vital signs at Screening.\n3. Abnormal QTcF interval or prolongation at Screening.\n4. Any other clinically significant finding on ECG at the Screening visit.\n5. Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and previous COVID 19 infection with last 12 months that required hospitalization.\n6. Unstable or changes Psychotropic treatment 2 weeks prior to screening\n7. Excluded concomitant treatments.\n8. Actively undergoing regression or loss of skills.\n9. Unstable seizure profile.\n10. Current clinically significant renal conditions and abnormalities\n11. Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment.\n12. Current clinically significant hypo- or hyperthyroidism, Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled Type 1 or Type 2 diabetes.\n13. Has planned surgery during the study.\n14. History of, or current, cerebrovascular disease or brain trauma.\n15. History of, or current catatonia or catatonia-like symptoms.\n16. History of, or current, malignancy.\n17. Current major or persistent depressive disorder (including bipolar depression).\n18. Significant, uncorrected visual or uncorrected hearing impairment.\n19. Allergy to strawberry.\n20. Positive pregnancy test\n21. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study'}, 'identificationModule': {'nctId': 'NCT05025332', 'acronym': 'PTHS-001', 'briefTitle': 'An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Neuren Pharmaceuticals Limited'}, 'officialTitle': 'An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)', 'orgStudyIdInfo': {'id': 'NEU-2591-PTHS-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'NNZ-2591', 'description': 'NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.', 'interventionNames': ['Drug: NNZ-2591']}], 'interventions': [{'name': 'NNZ-2591', 'type': 'DRUG', 'otherNames': ['Cyclo-L-Glycyl-L-2-Allylproline'], 'description': 'NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.', 'armGroupLabels': ['NNZ-2591']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama at Birmingham', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California at San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': "Children's Hospital Colorado", 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '60612', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Rush University Medical Center', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '75390', 'city': 'Dallas', 'state': 'Texas', 'country': 'United States', 'facility': 'UT Southwestern', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}], 'overallOfficials': [{'name': 'James Shaw', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Neuren Pharmaceuticals'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Neuren Pharmaceuticals Limited', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}