Ignite Creation Date:
2025-12-24 @ 7:48 PM
Ignite Modification Date:
2026-03-06 @ 4:01 PM
Study NCT ID:
NCT03344003
Status:
TERMINATED
Last Update Posted:
2024-08-09
First Post:
2017-11-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006467', 'term': 'Hemophilia A'}], 'ancestors': [{'id': 'D025861', 'term': 'Blood Coagulation Disorders, Inherited'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D020147', 'term': 'Coagulation Protein Disorders'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D014841', 'term': 'von Willebrand Factor'}, {'id': 'D005169', 'term': 'Factor VIII'}], 'ancestors': [{'id': 'D001779', 'term': 'Blood Coagulation Factors'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D011498', 'term': 'Protein Precursors'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Sigurd.Knaub@octapharma.com', 'phone': '01554512141', 'title': 'Dr. Sigurd Knaub, Senior VP CR&D Haematology', 'organization': 'Octapharma AG'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Adverse drug reactions were monitored throughout the study from first treatment through to study termination, a maximum of 2 years', 'description': 'There were no treatment-related ADRs during the study', 'eventGroups': [{'id': 'EG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.', 'otherNumAtRisk': 8, 'deathsNumAtRisk': 8, 'otherNumAffected': 0, 'seriousNumAtRisk': 8, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 1, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Device-related infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Bronchial hyperreactivity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Respiratory distress', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Moderate and Severe Haemophilia A Patients With Inhibitors Achieving Complete or Partial Immune Tolerance Induction (ITI) Success', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Respective Cohort', 'description': 'This cohort was made up of patients who had received Wilate immune tolerance induction (ITI) therapy within three years of enrolment'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'This cohort consisted of patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate'}], 'classes': [{'categories': [{'title': 'Complete success', 'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}, {'title': 'Partial success', 'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}, {'title': 'Partial failure', 'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}, {'title': 'Complete failure', 'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From ITI start until termination of study, a maximum of 2 years', 'description': 'ITI success will be determined using predefined success criteria to analyze the proportion of patients achieving complete or partial ITI success. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre \\<0.6BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental in vivo recovery (IVR) of FVIII in the normal range (≥66% of normal); 3) FVIII half-life ≥6 hours Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to \\<5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, efficacy data was not collected for enrolled patients in the prospective cohort'}, {'type': 'SECONDARY', 'title': 'Time Necessary to Achieve Complete or Partial ITI Success', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Time to achieve complete or partial ITI success will be determined using predefined success criteria. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre \\<0.6 BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental IVR of FVIII in the normal range (≥66% of normal) ; 3) FVIII half-life ≥6 hours. Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to \\<5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.\n\n0 participants analysed for this outcome due to termination of study.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'In Case of Complete or Partial ITI Success, Duration of Immune Tolerance', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Time from start of ITI success to end of study period', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Bleeding Frequency While on Wilate or Nuwiq ITI Treatment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Bleeding episodes occurring during the study period will be documented by the patient or their parents in a patient study diary.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Association of Inhibitor Titres With the Probability of ITI Success', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Inhibitor titre will be assessed at the start of and throughout ITI treatment, including peak inhibitor titres, with the probability of ITI success.\n\nITI success will be determined using predefined success criteria. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre \\<0.6 BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental IVR of FVIII in the normal range (≥66% of normal) ; 3) FVIII half-life ≥6 hours. Wilate or Nuwiq infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to \\<5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Use of Bypassing Agents Before and During ITI Treatment With Wilate or Nuwiq', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': '12 months before the start of ITI with Wilate or Nuwiq to a maximum of 5 years from starting ITI with Wilate or Nuwiq', 'description': "Use of bypassing agents is at the discretion of the Investigator, either to treat bleeding or to provide prophylactic therapy. As long as the patient's inhibitor level is ≥0.6 Bethesda units (BU), treatment of BEs may, in addition to FVIII treatment, require the administration of activated prothrombin complex concentrates (aPCC) or recombinant FVIIa.", 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Use of Emicizumab (Hemlibra) During ITI Treatment With Wilate or Nuwiq', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'The dosing and frequency of emicizumab (Hemlibra) used is at the discretion of the Investigator. As a general guidance, the recommended dose is 3mg/kg once weekly for the first 4 weeks, followed by 1.5mg/kg once weekly, administered as a subcutaneous injection, as per the product monograph.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Relapse Rate Following Complete or Partial Successful ITI Using Wilate or Nuwiq', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Reoccurrence of \\>0.6 BU in at least 2 consecutive blood samples after having reached the prophylactic treatment phase; a further ITI initiation (re-start) with Wilate or Nuwiq is at the discretion of the Investigator.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Time to Relapse Following Complete or Partial Successful ITI Using Wilate or Nuwiq', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Time to reoccurrence of \\>0.6 BU in at least 2 consecutive blood samples after having reached the prophylactic treatment phase; a further ITI initiation (re-start) with Wilate or Nuwiq is at the discretion of the Investigator.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}, {'type': 'SECONDARY', 'title': 'Adherence With the ITI Regimen', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'OG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}], 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'During ITI, any injections of Wilate or Nuwiq will be recorded in the patient study diary. The treating physician will review and verify the information provided by the patient.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The retrospective cohort was made up of 8 patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment. All patients had evaluable hemophilia A with an inhibitor against FVIII. The treatment regimen, doses, dosing intervals and dose adjustments were determined at the discretion of the treating physician. A usual dose for long-term prophylaxis against bleeding in patients with severe hemophilia A is 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days.\n\nAll enrolled patients were treated with Wilate. No patient discontinued the study before the study was terminated.'}, {'id': 'FG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The prospective cohort was made up of 6 patients who were currently receiving Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate. All patients had evaluable hemophilia A with an inhibitor against FVIII. The treatment regimen, doses, dosing intervals and dose adjustments were determined at the discretion of the treating physician. A usual dose for long-term prophylaxis against bleeding in patients with severe hemophilia A is 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days.\n\nAll enrolled patients were treated with Wilate. No patient discontinued the study before the study was terminated.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'comment': 'Study terminated prior to planned completion', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Switched to alternative treatment', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Experienced a better response with recombinant activated factor VII (rFVIIa)', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '14', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Wilate® Retrospective Cohort', 'description': 'The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment.'}, {'id': 'BG001', 'title': 'Wilate® Prospective Cohort', 'description': 'The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '10.6', 'spread': '5.2', 'groupId': 'BG000'}, {'value': '14.8', 'spread': '7.3', 'groupId': 'BG001'}, {'value': '12.4', 'spread': '6.1', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '14', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'categories': [{'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': 'Other', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Missing', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Blood type', 'classes': [{'categories': [{'title': 'O', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'A', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}, {'title': 'B', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'AB', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Missing', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Severity of hemophilia A', 'classes': [{'categories': [{'title': 'Mild', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}, {'title': 'Moderate', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Severe', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}, {'title': 'Missing', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Moderate Hemophilia was defined as the patient having a FVIII activity level of between 1-5%. Severe Hemophilia was defined as the patient having a FVIII activity level below 1%.', 'unitOfMeasure': 'Participants'}, {'title': 'FVIII mutation', 'classes': [{'categories': [{'title': 'Intron 22 Inversion', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}, {'title': 'Intron 1 Inversion', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Missense mutations', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Unknown', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'Missing', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Previous inhibitor treatment', 'classes': [{'categories': [{'title': 'Yes', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}, {'title': 'No', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-10-08', 'size': 1005984, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-06-06T11:06', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 14}, 'patientRegistry': False}, 'statusModule': {'whyStopped': 'Study terminated as enrolled patients rolled over into a large international study in the same indication', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2018-06-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2020-11-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-03-06', 'studyFirstSubmitDate': '2017-11-08', 'resultsFirstSubmitDate': '2022-02-24', 'studyFirstSubmitQcDate': '2017-11-14', 'lastUpdatePostDateStruct': {'date': '2024-08-09', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-03-06', 'studyFirstPostDateStruct': {'date': '2017-11-17', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-08-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-11-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Moderate and Severe Haemophilia A Patients With Inhibitors Achieving Complete or Partial Immune Tolerance Induction (ITI) Success', 'timeFrame': 'From ITI start until termination of study, a maximum of 2 years', 'description': 'ITI success will be determined using predefined success criteria to analyze the proportion of patients achieving complete or partial ITI success. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre \\<0.6BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental in vivo recovery (IVR) of FVIII in the normal range (≥66% of normal); 3) FVIII half-life ≥6 hours Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to \\<5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.'}], 'secondaryOutcomes': [{'measure': 'Time Necessary to Achieve Complete or Partial ITI Success', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Time to achieve complete or partial ITI success will be determined using predefined success criteria. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre \\<0.6 BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental IVR of FVIII in the normal range (≥66% of normal) ; 3) FVIII half-life ≥6 hours. Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to \\<5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.\n\n0 participants analysed for this outcome due to termination of study.'}, {'measure': 'In Case of Complete or Partial ITI Success, Duration of Immune Tolerance', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Time from start of ITI success to end of study period'}, {'measure': 'Bleeding Frequency While on Wilate or Nuwiq ITI Treatment', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Bleeding episodes occurring during the study period will be documented by the patient or their parents in a patient study diary.'}, {'measure': 'Association of Inhibitor Titres With the Probability of ITI Success', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Inhibitor titre will be assessed at the start of and throughout ITI treatment, including peak inhibitor titres, with the probability of ITI success.\n\nITI success will be determined using predefined success criteria. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre \\<0.6 BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental IVR of FVIII in the normal range (≥66% of normal) ; 3) FVIII half-life ≥6 hours. Wilate or Nuwiq infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to \\<5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.'}, {'measure': 'Use of Bypassing Agents Before and During ITI Treatment With Wilate or Nuwiq', 'timeFrame': '12 months before the start of ITI with Wilate or Nuwiq to a maximum of 5 years from starting ITI with Wilate or Nuwiq', 'description': "Use of bypassing agents is at the discretion of the Investigator, either to treat bleeding or to provide prophylactic therapy. As long as the patient's inhibitor level is ≥0.6 Bethesda units (BU), treatment of BEs may, in addition to FVIII treatment, require the administration of activated prothrombin complex concentrates (aPCC) or recombinant FVIIa."}, {'measure': 'Use of Emicizumab (Hemlibra) During ITI Treatment With Wilate or Nuwiq', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'The dosing and frequency of emicizumab (Hemlibra) used is at the discretion of the Investigator. As a general guidance, the recommended dose is 3mg/kg once weekly for the first 4 weeks, followed by 1.5mg/kg once weekly, administered as a subcutaneous injection, as per the product monograph.'}, {'measure': 'Relapse Rate Following Complete or Partial Successful ITI Using Wilate or Nuwiq', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Reoccurrence of \\>0.6 BU in at least 2 consecutive blood samples after having reached the prophylactic treatment phase; a further ITI initiation (re-start) with Wilate or Nuwiq is at the discretion of the Investigator.'}, {'measure': 'Time to Relapse Following Complete or Partial Successful ITI Using Wilate or Nuwiq', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'Time to reoccurrence of \\>0.6 BU in at least 2 consecutive blood samples after having reached the prophylactic treatment phase; a further ITI initiation (re-start) with Wilate or Nuwiq is at the discretion of the Investigator.'}, {'measure': 'Adherence With the ITI Regimen', 'timeFrame': 'A maximum period of 5 years from ITI start', 'description': 'During ITI, any injections of Wilate or Nuwiq will be recorded in the patient study diary. The treating physician will review and verify the information provided by the patient.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hemophilia A']}, 'descriptionModule': {'briefSummary': 'Uncontrolled, multi-centre, non-interventional study with a prospective and a retrospective cohort, to evaluate the efficacy of Wilate or Nuwiq in achieving complete or partial immune tolerance induction (ITI) success in severe and moderate haemophilia A patients with inhibitors'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'A total of at least 80 patients were planned, at least 40 in the prospective cohort and 40 in the retrospective cohort. Due to study termination, only 14 patients were enrolled.', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Male patients of any age with moderate or severe haemophilia A.\n* Patients with a first occurrence of inhibitors, inhibitors refractory to previous ITI attempt(s), or relapsed inhibitors to FVIII, with an inhibitor titre of ≥0.6 BU measured on 2 separate occasions at least 2 weeks apart.\n* Informed written consent from the patient and/or the patient's parent(s) or legal guardian(s)\n\nFor patients in the prospective cohort:\n\n* Patients who are currently on Wilate or Nuwiq ITI, have just initiated ITI, or are planned to initiate ITI treatment with Wilate or Nuwiq.\n\nFor patients in the retrospective cohort:\n\n* Patients having received Wilate or Nuwiq ITI before entry into this study. Retrospective data will be collected for a maximum of 3 years before enrolment into the study. To be eligible, the following information is needed:\n* Wilate or Nuwiq treatment details (start date, dose, treatment frequency, and dose change).\n* Reliably documented bleeding frequency.\n* FVIII inhibitor titres.\n* FVIII half-life.\n* FVIII IVR.\n\nExclusion Criteria:\n\nPatients who meet any of the following criteria are not eligible for the study:\n\n* Congenital or acquired bleeding disorders other than haemophilia A.\n* A history of hypersensitivity to blood products and/or plasma-derived FVIII concentrates.\n* Inability to speak/read English or French well enough to provide consent and adhere to the study.\n* People who are receiving other non-factor therapies, e.g. concizumab"}, 'identificationModule': {'nctId': 'NCT03344003', 'acronym': 'PREVAIL', 'briefTitle': 'Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq', 'organization': {'class': 'INDUSTRY', 'fullName': 'Octapharma'}, 'officialTitle': 'Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq - A Canadian Study', 'orgStudyIdInfo': {'id': 'WIL-26'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Wilate or Nuwiq prospective cohort', 'description': 'Evaluable haemophilia A patients with an inhibitor against FVIII enrolled prospectively', 'interventionNames': ['Drug: Wilate or Nuwiq']}, {'label': 'Wilate or Nuwiq retrospective cohort', 'description': 'Evaluable haemophilia A patients with an inhibitor against FVIII enrolled retrospectively', 'interventionNames': ['Drug: Wilate or Nuwiq']}], 'interventions': [{'name': 'Wilate or Nuwiq', 'type': 'DRUG', 'otherNames': ['Wilate: Human von Willebrand factor / human coagulation factor VIII. Nuwiq: recombinant factor VIII (rhFVIII)'], 'description': 'Wilate or Nuwiq administered via intravenous injection', 'armGroupLabels': ['Wilate or Nuwiq prospective cohort', 'Wilate or Nuwiq retrospective cohort']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'facility': "Stollery children's hospital, University of Alberta", 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'city': 'Ottawa', 'state': 'Ontario', 'country': 'Canada', 'facility': "Children's Hospital of Eastern Ontario", 'geoPoint': {'lat': 45.41117, 'lon': -75.69812}}, {'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Hamilton Health Science center', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'Sri Adapa', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Octapharma'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Octapharma', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}