Ignite Creation Date:
2025-12-25 @ 1:40 AM
Ignite Modification Date:
2025-12-25 @ 11:56 PM
Study NCT ID:
NCT05890794
Status:
COMPLETED
Last Update Posted:
2025-02-27
First Post:
2023-05-10
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007014', 'term': 'Hypophosphatasia'}], 'ancestors': [{'id': 'D008664', 'term': 'Metal 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': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'office@am-pharma.com', 'phone': '31 (0)30 228 92 22', 'title': 'AM-Pharma Office', 'organization': 'AM-Pharma'}, 'certainAgreement': {'otherDetails': "The PI may publish the study results but must submit the publication to the sponsor for review at least 60 days prior to publication. The sponsor may request changes/removals of sponsor information. The PI should remove such information if the correct presentation of the results is still ensured. The PI must consider the sponsor's other comments but must not adopt them. If publication could affect the patentability of the invention, the sponsor may request an additional period of up to 120 days.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Day 1 to Day 15', 'eventGroups': [{'id': 'EG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single dose administered intravenously over 1 hour\n\nIlofotase Alfa, 0.8 mg/kg: Biological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 1, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single dose administered intravenously over 1 hour\n\nIlofotase Alfa, 3.2 mg/kg: Biological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 3, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Overall', 'description': 'Single dose administered intravenously over 1 hour\n\nIlofotase Alfa, 0.8 or 3.2 mg/kg: Biological: single 1-hour intravenous infusion of 0.8 or 3.2 mg/kg ilofotase alfa', 'otherNumAtRisk': 12, 'deathsNumAtRisk': 12, 'otherNumAffected': 4, 'seriousNumAtRisk': 12, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Restless arm syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Restless legs syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '-36.46', 'spread': '11.502', 'groupId': 'OG000'}, {'value': '-77.31', 'spread': '16.113', 'groupId': 'OG001'}, {'value': '-56.88', 'spread': '25.165', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0005', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '40.85', 'ciLowerLimit': '22.842', 'ciUpperLimit': '58.858', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline between dose groups of ilofotase alfa by a 2-sided t-test for PPi.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'A 2-sided t-test was carried out to determine whether there is a difference in means between the 0.8 mg/kg and 3.2 mg/kg dose groups.', 'nonInferiorityComment': 'The difference in dose group means (0.8 mg/kg - 3.2 mg/kg) was calculated.'}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in LS Means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-11.17', 'ciLowerLimit': '-16.52', 'ciUpperLimit': '-5.82', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.681', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline (LS Means) between dose groups of ilofotase alfa by a mixed model repeated measures (MMRM) analysis for PPi.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'The difference between LS Means of change from baseline between dose groups was calculated. The analysis was performed using an MMRM model with fixed effects for baseline value, dose group, timepoint, interaction between dose group and timepoint, as well as random effects for patient and error'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PPi serum concentration is calculated for all post-dose PPi measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= \\[(PPi( x)-PPi(baseline))/PPi(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12)).", 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All randomized patients.'}, {'type': 'PRIMARY', 'title': "Maximum Percent Change From Baseline in Pyridoxal 5'-Phosphate (PLP)", 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '-34.68', 'spread': '8.898', 'groupId': 'OG000'}, {'value': '-65.56', 'spread': '6.559', 'groupId': 'OG001'}, {'value': '-50.12', 'spread': '17.768', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '30.89', 'ciLowerLimit': '20.831', 'ciUpperLimit': '40.941', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline between dose groups of ilofotase alfa by a 2-sided t-test for PLP.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'A 2-sided t-test was carried out to determine whether there is a difference in means between the 0.8 mg/kg and 3.2 mg/kg dose groups.', 'nonInferiorityComment': 'The difference in dose group means (0.8 mg/kg - 3.2 mg/kg) was calculated.'}, {'pValue': '0.0024', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in LS Means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-22.51', 'ciLowerLimit': '-35.81', 'ciUpperLimit': '-9.20', 'pValueComment': 'Significant test: two-sided; significance level 5%.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '6.289', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline (LS Means) between dose groups of ilofotase alfa by an MMRM analysis for PLP.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'The difference between LS Means of change from baseline between dose groups was calculated. The analysis was performed using an MMRM model with fixed effects for baseline value, dose group, timepoint, interaction between dose group and timepoint, as well as random effects for patient and error.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PLP serum concentration is calculated for all post-dose PLP measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= \\[(PLP( x)-PLP(baseline))/PLP(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12)).", 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All randomized patients.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Maximum Percent Change From Baseline in Alkaline Phosphatase (ALP) Activity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '2685.57', 'spread': '1492.991', 'groupId': 'OG000'}, {'value': '7021.23', 'spread': '2063.878', 'groupId': 'OG001'}, {'value': '4853.40', 'spread': '2841.847', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0019', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-4335.66', 'ciLowerLimit': '-6652.753', 'ciUpperLimit': '-2018.576', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline between dose groups of ilofotase alfa by a 2-sided t-test for ALP activity.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'A 2-sided t-test was carried out to determine whether there is a difference in means between the 0.8 mg/kg and 3.2 mg/kg dose groups.', 'nonInferiorityComment': 'The difference in dose group means (0.8 mg/kg - 3.2 mg/kg) was calculated.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in ALP Activity is calculated for all post-dose ALP measures recorded from Day 2 to Day 10.\n\nPer patient, 9 measurements were done: 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…9) is calculated: PCBL(x)= (ALP(x)-ALP(baseline))/ALP(baseline)\\*100, \\[x=1,...,9\\].\n\nThe subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(9))", 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All randomized patients.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Maximum Percent Change From Baseline in Urine Phosphoethanolamine (PEA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '-28.58', 'spread': '15.161', 'groupId': 'OG000'}, {'value': '-51.82', 'spread': '19.614', 'groupId': 'OG001'}, {'value': '-40.20', 'spread': '20.573', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0693', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '23.25', 'ciLowerLimit': '-2.319', 'ciUpperLimit': '48.812', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline between dose groups of ilofotase alfa by a 2-sided t-test for urine PEA.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'A 2-sided t-test was carried out to determine whether there is a difference in means between the 0.8 mg/kg and 3.2 mg/kg dose groups.', 'nonInferiorityComment': 'The difference in dose group means (0.8 mg/kg - 3.2 mg/kg) was calculated.'}, {'pValue': '0.7086', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in LS Means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-8.76', 'ciLowerLimit': '-57.88', 'ciUpperLimit': '40.35', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '22.986', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline (LS Means) between dose groups of ilofotase alfa by an MMRM analysis for urine PEA.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'The difference between LS Means of change from baseline between dose groups was calculated. The analysis was performed using an MMRM model with fixed effects for baseline value, dose group, timepoint, interaction between dose group and timepoint, as well as random effects for patient and error.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PEA concentration is calculated for all post-dose PEA measures recorded from Day 2 to Day 10. Per patient, 9 measurements were done: 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…9) is calculated: PCBL(x)= \\[(PEA( x)-PEA(baseline))/PEA(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(9)).", 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All randomized patients.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Maximum Percent Change From Baseline in Pyridoxal (PL).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '409.76', 'spread': '138.504', 'groupId': 'OG000'}, {'value': '222.33', 'spread': '91.332', 'groupId': 'OG001'}, {'value': '316.05', 'spread': '148.635', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0199', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '187.43', 'ciLowerLimit': '36.516', 'ciUpperLimit': '338.344', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline between dose groups of ilofotase alfa by a 2-sided t-test for PL.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'A 2-sided t-test was carried out to determine whether there is a difference in means between the 0.8 mg/kg and 3.2 mg/kg dose groups.', 'nonInferiorityComment': 'The difference in dose group means (0.8 mg/kg - 3.2 mg/kg) was calculated.'}, {'pValue': '0.2034', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in LS Means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-12.51', 'ciLowerLimit': '-31.92', 'ciUpperLimit': '6.89', 'pValueComment': 'Significant test: 2-sided; significance level 5%', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '9.767', 'groupDescription': 'Analysis of the difference in relative maximum change from baseline (LS Means) between dose groups of ilofotase alfa by an MMRM analysis for PL.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'The difference between LS Means of change from baseline between dose groups was calculated. The analysis was performed using an MMRM model with fixed effects for baseline value, dose group, timepoint, interaction between dose group and timepoint, as well as random effects for patient and error.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PL serum concentration is calculated for all post-dose PL measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= \\[(PL( x)-PL(baseline))/PL(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12)).", 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All randomized patients.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Maximum Fold Change From Baseline in PL/PLP Ratio', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '6.9145', 'spread': '1.83957', 'groupId': 'OG000'}, {'value': '7.8062', 'spread': '2.70554', 'groupId': 'OG001'}, {'value': '7.3604', 'spread': '2.25440', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.5195', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.89', 'ciLowerLimit': '-3.868', 'ciUpperLimit': '2.084', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'groupDescription': 'Analysis of the difference in fold change from baseline between dose groups of ilofotase alfa by a 2-sided t-test for PL/PLP ratio.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'A 2-sided t-test was carried out to determine whether there is a difference in means between the 0.8 mg/kg and 3.2 mg/kg dose groups.', 'nonInferiorityComment': 'The difference in dose group means (0.8 mg/kg - 3.2 mg/kg) was calculated.'}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in LS Means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.01', 'ciLowerLimit': '0.69', 'ciUpperLimit': '1.33', 'pValueComment': 'Significant test: 2-sided; significance level 5%.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.161', 'groupDescription': 'Analysis of the difference in fold change form baseline (LS Means) between dose levels of ilofotase alfa by an MMRM analysis for PL/PLP ratio.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'The difference between LS Means of fold change from baseline between dose groups was calculated. The analysis was performed using an MMRM model with fixed effects for baseline value, dose group, timepoint, interaction between dose group and timepoint, as well as random effects for patient and error.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 10', 'description': "Fold Change from BaseLine (FCBL) in PL/PLP ratio is calculated for all post-dose PL/PLP ratio measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Fold Change from BaseLine for measurement x (x=1,…12) is calculated: FCBL(x)= (PL/PLPratio( x) / PL/PLPratio(baseline)). The subject's maximum fold change from baseline is defined as the Max (FCBL(1), …, FCBL(12)).", 'unitOfMeasure': 'fold change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All randomized patients.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Treatment-emergent Adverse Events (TEAEs)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '12', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'OG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'OG002', 'title': 'Overall', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg or 3.2 mg/kg ilofotase alfa'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '4', 'groupId': 'OG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Day 1 to Day 15', 'description': 'Any untoward medical occurrence in a patient enrolled and treated in the clinical trial regardless of its causal relationship to the trial medication.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients who received trial medication were included in the population for the safety analysis.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'FG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': '12 patients were enrolled, screened and randomized (6 to the 0.8 mg ilofotase alfa dose group, 6 to the 3.2 mg ilofotase alfa dose group)'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': '0.8 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa'}, {'id': 'BG001', 'title': '3.2 mg/kg Ilofotase Alfa', 'description': 'Single, 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '49.5', 'groupId': 'BG000', 'lowerLimit': '41', 'upperLimit': '62'}, {'value': '51.0', 'groupId': 'BG001', 'lowerLimit': '30', 'upperLimit': '68'}, {'value': '51.0', 'groupId': 'BG002', 'lowerLimit': '30', 'upperLimit': '68'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}], 'populationDescription': 'Intention-to-treat population = all randomized patients'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2023-03-30', 'size': 1371420, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2024-09-09T11:51', 'hasProtocol': True}, {'date': '2023-06-05', 'size': 5308024, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2024-09-09T12:03', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Trial is masked for received dose; type of drug received is open-label'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '2 doses will be compared'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 12}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2023-05-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-02', 'completionDateStruct': {'date': '2023-07-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-02-05', 'studyFirstSubmitDate': '2023-05-10', 'resultsFirstSubmitDate': '2024-09-09', 'studyFirstSubmitQcDate': '2023-05-26', 'lastUpdatePostDateStruct': {'date': '2025-02-27', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-02-05', 'studyFirstPostDateStruct': {'date': '2023-06-06', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-02-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-07-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Maximum Percent Change From Baseline in Alkaline Phosphatase (ALP) Activity', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in ALP Activity is calculated for all post-dose ALP measures recorded from Day 2 to Day 10.\n\nPer patient, 9 measurements were done: 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…9) is calculated: PCBL(x)= (ALP(x)-ALP(baseline))/ALP(baseline)\\*100, \\[x=1,...,9\\].\n\nThe subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(9))"}, {'measure': 'Maximum Percent Change From Baseline in Urine Phosphoethanolamine (PEA)', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PEA concentration is calculated for all post-dose PEA measures recorded from Day 2 to Day 10. Per patient, 9 measurements were done: 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…9) is calculated: PCBL(x)= \\[(PEA( x)-PEA(baseline))/PEA(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(9))."}, {'measure': 'Maximum Percent Change From Baseline in Pyridoxal (PL).', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PL serum concentration is calculated for all post-dose PL measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= \\[(PL( x)-PL(baseline))/PL(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12))."}, {'measure': 'Maximum Fold Change From Baseline in PL/PLP Ratio', 'timeFrame': 'Day 1 to Day 10', 'description': "Fold Change from BaseLine (FCBL) in PL/PLP ratio is calculated for all post-dose PL/PLP ratio measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Fold Change from BaseLine for measurement x (x=1,…12) is calculated: FCBL(x)= (PL/PLPratio( x) / PL/PLPratio(baseline)). The subject's maximum fold change from baseline is defined as the Max (FCBL(1), …, FCBL(12))."}, {'measure': 'Treatment-emergent Adverse Events (TEAEs)', 'timeFrame': 'Day 1 to Day 15', 'description': 'Any untoward medical occurrence in a patient enrolled and treated in the clinical trial regardless of its causal relationship to the trial medication.'}], 'primaryOutcomes': [{'measure': 'Maximum Percent Change From Baseline in Extracellular Inorganic Pyrophosphate (PPi)', 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PPi serum concentration is calculated for all post-dose PPi measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= \\[(PPi( x)-PPi(baseline))/PPi(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12))."}, {'measure': "Maximum Percent Change From Baseline in Pyridoxal 5'-Phosphate (PLP)", 'timeFrame': 'Day 1 to Day 10', 'description': "Percent Change from BaseLine (PCBL) in PLP serum concentration is calculated for all post-dose PLP measures recorded from Day 1 to Day 10. Per patient, 12 measurements were done: 3 at Day 1 and 1 each day from Day 2 to Day 10. The Percent Change from BaseLine for measurement x (x=1,…12) is calculated: PCBL(x)= \\[(PLP( x)-PLP(baseline))/PLP(baseline)\\]\\*100. The subject's maximum percent change from baseline is defined as the Max (PCBL(1), …, PCBL(12))."}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Enzyme replacement therapy'], 'conditions': ['Hypophosphatasia']}, 'descriptionModule': {'briefSummary': "The goal of this clinical trial is to compare the effectiveness of two doses of ilofotase alfa, an enzyme replacement treatment, in patients with hypophosphatasia (HPP). The main question it aims to answer is if the harmful accumulating levels of extracellular inorganic pyrophosphate (PPi) and pyridoxal 5'-phosphate (PLP) can be reduced with ilofotase alfa.\n\nResearchers will compare the two doses of ilofotase alfa to see if treatment effects differ between the doses.", 'detailedDescription': 'Recombinant human alkaline phosphatase (ilofotase alfa) is a full-length human chimeric alkaline phosphatase (ALP) that could benefit patients with hypophosphatasia (HPP), which is characterized by low activity of tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP).\n\nThis is a pilot trial for a potential future trial aimed at identifying whether treatment with ilofotase alfa can normalize circulating levels of PPi, PLP and other biochemical markers of TNSALP deficiency along with the safety/tolerability of different doses of ilofotase alfa. The trial is designed as a single-center, open-label, randomized, parallel group clinical trial in adult patients with HPP. Two different dose levels (0.8 mg/kg and 3.2 mg/kg) of ilofotase alfa will be assessed.\n\nParticipants will receive a single dose of ilofotase alfa, administered as a 1-hour intravenous infusion on Study Day 1. Participants will stay at the research center for a total of 12 days; from 2 days before study drug administration (run-in) to 10 days after treatment. An additional follow-up assessment is scheduled 14 days after administration of ilofotase alfa.\n\nBlood and urine samples will be taken daily for drug concentration and laboratory measurements assessing safety and effectiveness of treatment. In addition physical examinations will be performed on Day 1 and as needed afterwards.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Genetically confirmed variant in the tissue-nonspecific isozyme alkaline phosphatase (ALPL)-Gene.\n* Clinical symptoms of HPP.\n* Medical history with 1) at least two independent measures of Alkaline Phosphatase (ALP) below lower level of normal (LLN) and 2) at least one measurement of either PPi or PLP above upper level of normal (ULN).\n* Provision of signed and dated informed consent form (ICF) in accordance with local regulations at screening.\n* Patients must agree not to get pregnant/not to get their partner pregnant, during the trial. Consequently, patients must agree to use adequate contraception as detailed in study protocol.\n\nExclusion Criteria:\n\n* Participant is unable or unwilling to participate in all scheduled visits and perform all protocol-mandated assessments.\n* Has a known or suspected hypersensitivity to ilofotase alfa or any components of the formulation used.\n* Body weight \\< 40 kilogram and \\> 120 kilogram.\n* Patient has a history of clinically significant abnormalities or of any illness that, in the opinion of the trial investigator, might confound the results of the trial or pose an additional risk to the patient by their participation in the trial.\n* NSAID use in the past 2 weeks.\n* Use of corticosteroids in the past 4 weeks.\n* Use of compounds intended to interfere with bone metabolism (e.g. Denosumab, Teriparatide, Romosozumab, Raloxifene) in the past 3 months.\n* Use of bisphosphonates in the past 2 years.\n* Participation in a drug trial within 60 days, or five times the half-life of the drug, whichever is longer, prior to administration of ilofotase alfa.\n* Use of asfotase alfa in the previous 3 months. Patients will not be withheld from approved asfotase alfa if medically indicated.\n* A patient who is currently pregnant or lactating.\n* Use of supplements including Vitamin B6.'}, 'identificationModule': {'nctId': 'NCT05890794', 'briefTitle': 'Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia', 'organization': {'class': 'INDUSTRY', 'fullName': 'AM-Pharma'}, 'officialTitle': 'Open-Label Pilot Trial to Evaluate the Effects of Ilofotase Alfa on Biomarkers in Adult Patients With Hypophosphatasia', 'orgStudyIdInfo': {'id': 'AP-recAP-HPP-01-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '0.8 mg/kg ilofotase alfa', 'description': 'Single dose administered intravenously over 1 hour', 'interventionNames': ['Biological: Ilofotase Alfa, 0.8 mg/kg']}, {'type': 'EXPERIMENTAL', 'label': '3.2 mg/kg ilofotase alfa', 'description': 'Single dose administered intravenously over 1 hour', 'interventionNames': ['Biological: Ilofotase Alfa, 3.2 mg/kg']}], 'interventions': [{'name': 'Ilofotase Alfa, 0.8 mg/kg', 'type': 'BIOLOGICAL', 'otherNames': ['recAP'], 'description': 'Biological: single 1-hour intravenous infusion of 0.8 mg/kg ilofotase alfa', 'armGroupLabels': ['0.8 mg/kg ilofotase alfa']}, {'name': 'Ilofotase Alfa, 3.2 mg/kg', 'type': 'BIOLOGICAL', 'otherNames': ['recAP'], 'description': 'Biological: single 1-hour intravenous infusion of 3.2 mg/kg ilofotase alfa', 'armGroupLabels': ['3.2 mg/kg ilofotase alfa']}]}, 'contactsLocationsModule': {'locations': [{'zip': '97074', 'city': 'Würzburg', 'country': 'Germany', 'facility': 'Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH', 'geoPoint': {'lat': 49.79391, 'lon': 9.95121}}], 'overallOfficials': [{'name': 'Dr Seefried', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Osteologie / Klinische Studieneinheit, Orthopädische Klinik - KLH, Würzburg, Germany'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'AM-Pharma', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}