Ignite Creation Date:
2025-12-25 @ 1:07 AM
Ignite Modification Date:
2025-12-27 @ 2:12 AM
Study NCT ID:
NCT00947193
Status:
TERMINATED
Last Update Posted:
2020-06-16
First Post:
2009-07-23
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Study of Ataluren (PTC124) in Hemophilia A and B
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006467', 'term': 'Hemophilia A'}, {'id': 'D002836', 'term': 'Hemophilia B'}], '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'}, {'id': 'D040181', 'term': 'Genetic Diseases, X-Linked'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C515878', 'term': 'ataluren'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'medinfo@ptcbio.com', 'phone': '1-866-562-4620', 'title': 'Patient Advocacy', 'organization': 'PTC Therapeutics, Inc.'}, 'certainAgreement': {'otherDetails': 'The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Baseline up to Day 28', 'description': 'Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.', 'eventGroups': [{'id': 'EG000', 'title': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.", 'otherNumAtRisk': 13, 'otherNumAffected': 8, 'seriousNumAtRisk': 13, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Conduction disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Asthenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Haematuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Dysuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}, {'term': 'Haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 3}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 11.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With a Plasma FVIII/FIX Activity Response at Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': '10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 14', 'description': 'A plasma FVIII/FIX activity response was defined as an end-of-treatment (Day 14) activity of ≥1%.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug and completed the study.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With a Change From Baseline in Plasma Anti-FVIII/FIX Inhibitor Titers at Day 14', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': '10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline and Day 14', 'description': 'To assess the change from Baseline in plasma anti-FVIII/FIX inhibitor titers, it was determined if any potential antibodies were neutralizing using the Bethesda assay. The Bethesda assay demonstrates antibodies that are neutralizing by quantifying residual FVIII/FIX activity in normal plasma after serial dilutions with participant plasma. For this assay, the neutralizing antibody threshold value was 0.6 Bethesda units (BU).', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug and completed the study.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'classes': [{'title': 'TEAEs', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}]}]}, {'title': 'TEAEs Related to Study Drug', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Severe TEAEs', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'SAEs', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': 'The relationship of TEAEs and SAEs to the study drugs was assessed as: probable related, possible related, unlikely related, and unrelated. The severity of TEAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0, as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). A summary of other non-serious adverse events (AEs) and all serious AEs, regardless of causality is located in Reported AE section.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'classes': [{'title': 'Hematology Assays', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Biochemistry Assays', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Adrenal Assays', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Urinalysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': 'The Investigator used his/her judgment in determining whether an abnormality was clinically significant, diagnostic evaluation was warranted, and potential interruption of ataluren was appropriate. Life-threatening (Grade 4) or severe (Grade 3) laboratory abnormalities were considered dose-limiting, although recurrent or persistent moderate (Grade 2) events were also considered dose-limiting in certain circumstances. Values considered abnormal included -Hematology: Serum total bilirubin Grade 2 (\\>1.5-3.0\\*upper limit of normal \\[ULN\\]) and Serum alanine aminotransferase, Serum aspartate aminotransferase, and Serum gamma glutamyl transferase Grade 2 (\\>2.5-3.0\\*ULN); -Adrenal: Plasma adrenocorticotropic hormone \\>ULN (and cortisol within normal limits); and -Renal: serum creatinine Grade 1 (\\>ULN-1.5\\*ULN) and Serum blood urea nitrogen ≥1.5-3.0\\*ULN. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug and had evaluable clinical laboratory data.'}, {'type': 'SECONDARY', 'title': 'Compliance With Ataluren Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'timeFrame': 'Baseline up to Day 28', 'description': 'Ataluren compliance as assessed by quantification of used and unused drug. Data were not collected or analyzed for this measure because participants were terminated early from the study.', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug, completed the study, and had evaluable compliance with ataluren administration data.'}, {'type': 'SECONDARY', 'title': 'Ataluren Plasma Exposure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': '10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'classes': [{'title': 'Pre-Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '14.7', 'groupId': 'OG000', 'lowerLimit': '5.94', 'upperLimit': '28.7'}]}]}, {'title': 'Post-Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '6.66', 'groupId': 'OG000', 'lowerLimit': '1.04', 'upperLimit': '28.3'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Day 10 (pre-dose) and Day 14 (post-dose)', 'description': 'The ataluren plasma concentrations before and 2 hours after the first morning dose at end of treatment was measured.', 'unitOfMeasure': 'microgram/milliliters (μg/mL)', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug, completed the study, and had evaluable plasma data.'}, {'type': 'SECONDARY', 'title': 'Occurrence of Bleeding Episodes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'classes': [{'title': 'Participants Who Experienced a Bleeding Episode', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': 'Spontaneous Right Hip Bleed', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Soft Tissue Bleed', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Right Knee Bleed', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Upper Shoulder Bleed', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline up to Day 28', 'description': 'Frequency, timing, anatomic location, and severity of any bleeding episodes were recorded. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': '5 mg/kg, 5 mg/kg, and 10 mg/kg Ataluren', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 milligrams/kilograms (mg/kg) in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}, {'id': 'FG001', 'title': '10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'Received at Least 1 Dose of Study Drug', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Factor VIII >1%', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'In this study, participants with HA or HB due to a nonsense mutation were recruited for the study.', 'preAssignmentDetails': 'Participants requiring treatment with Factor 8 (FVIII)/Factor 9 (FIX) concentrate during 14-day ataluren treatment could continue ataluren treatment for at least 14 days following discontinuing FVIII concentrate treatment for hemophilia type A (HA) and for at least 18 days following discontinuing FIX concentrate treatment for hemophilia type B (HB)'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment."}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '42', 'spread': '17.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All enrolled participants who received at least 1 dose of study drug.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 13}}, 'statusModule': {'whyStopped': 'Study was terminated early due to Sponsor decision and not reflective of adverse safety findings.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2009-10-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-05', 'dispFirstSubmitDate': '2019-04-01', 'completionDateStruct': {'date': '2011-08-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-05-28', 'studyFirstSubmitDate': '2009-07-23', 'dispFirstSubmitQcDate': '2019-04-01', 'resultsFirstSubmitDate': '2020-05-28', 'studyFirstSubmitQcDate': '2009-07-24', 'dispFirstPostDateStruct': {'date': '2019-04-08', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2020-06-16', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-05-28', 'studyFirstPostDateStruct': {'date': '2009-07-27', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-06-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2011-08-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With a Plasma FVIII/FIX Activity Response at Day 14', 'timeFrame': 'Baseline up to Day 14', 'description': 'A plasma FVIII/FIX activity response was defined as an end-of-treatment (Day 14) activity of ≥1%.'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With a Change From Baseline in Plasma Anti-FVIII/FIX Inhibitor Titers at Day 14', 'timeFrame': 'Baseline and Day 14', 'description': 'To assess the change from Baseline in plasma anti-FVIII/FIX inhibitor titers, it was determined if any potential antibodies were neutralizing using the Bethesda assay. The Bethesda assay demonstrates antibodies that are neutralizing by quantifying residual FVIII/FIX activity in normal plasma after serial dilutions with participant plasma. For this assay, the neutralizing antibody threshold value was 0.6 Bethesda units (BU).'}, {'measure': 'Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug', 'timeFrame': 'Baseline up to Day 28', 'description': 'The relationship of TEAEs and SAEs to the study drugs was assessed as: probable related, possible related, unlikely related, and unrelated. The severity of TEAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0, as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). A summary of other non-serious adverse events (AEs) and all serious AEs, regardless of causality is located in Reported AE section.'}, {'measure': 'Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters', 'timeFrame': 'Baseline up to Day 28', 'description': 'The Investigator used his/her judgment in determining whether an abnormality was clinically significant, diagnostic evaluation was warranted, and potential interruption of ataluren was appropriate. Life-threatening (Grade 4) or severe (Grade 3) laboratory abnormalities were considered dose-limiting, although recurrent or persistent moderate (Grade 2) events were also considered dose-limiting in certain circumstances. Values considered abnormal included -Hematology: Serum total bilirubin Grade 2 (\\>1.5-3.0\\*upper limit of normal \\[ULN\\]) and Serum alanine aminotransferase, Serum aspartate aminotransferase, and Serum gamma glutamyl transferase Grade 2 (\\>2.5-3.0\\*ULN); -Adrenal: Plasma adrenocorticotropic hormone \\>ULN (and cortisol within normal limits); and -Renal: serum creatinine Grade 1 (\\>ULN-1.5\\*ULN) and Serum blood urea nitrogen ≥1.5-3.0\\*ULN. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.'}, {'measure': 'Compliance With Ataluren Administration', 'timeFrame': 'Baseline up to Day 28', 'description': 'Ataluren compliance as assessed by quantification of used and unused drug. Data were not collected or analyzed for this measure because participants were terminated early from the study.'}, {'measure': 'Ataluren Plasma Exposure', 'timeFrame': 'Day 10 (pre-dose) and Day 14 (post-dose)', 'description': 'The ataluren plasma concentrations before and 2 hours after the first morning dose at end of treatment was measured.'}, {'measure': 'Occurrence of Bleeding Episodes', 'timeFrame': 'Baseline up to Day 28', 'description': 'Frequency, timing, anatomic location, and severity of any bleeding episodes were recorded. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Hemophilia A', 'Hemophilia B', 'Factor VIII', 'Factor IX', 'FVIII', 'FIX', 'Nonsense mutation', 'Premature stop codon', 'HA', 'HB', 'PTC124', 'Ataluren'], 'conditions': ['Hemophilia A', 'Hemophilia B']}, 'referencesModule': {'references': [{'pmid': '17389552', 'type': 'BACKGROUND', 'citation': 'Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44. doi: 10.1177/0091270006297140.'}, {'pmid': '17450125', 'type': 'BACKGROUND', 'citation': 'Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. doi: 10.1038/nature05756. Epub 2007 Apr 22.'}], 'seeAlsoLinks': [{'url': 'http://www.ptcbio.com', 'label': "PTC Therapeutics' website"}]}, 'descriptionModule': {'briefSummary': 'Hemophilia A (HA) and hemophilia B (HB) are inherited bleeding disorders caused by mutations in the gene for factor VIII (FVIII) and factor IX (FIX), respectively. These proteins are essential for blood clotting. The lack of FVIII/FIX can produce bleeding episodes that cause damage of the bone, muscles, joints, and tissues. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of the disease in approximately 10-30% of participants with hemophilia and results in severe manifestations. Ataluren (PTC124) is an orally delivered, investigational drug that acts to overcome the effects of the premature stop codon, potentially enabling the production of functional FVIII/FIX. This study is a Phase 2a trial evaluating the safety and efficacy of ataluren in participants with HA or HB due to a nonsense mutation. The main purpose of this study is to understand whether ataluren can safely increase FVIII/FIX activity levels.', 'detailedDescription': 'In this study, participants with hemophilia A or hemophilia B due to a nonsense mutation were treated with an investigational drug called ataluren (PTC124). Evaluation procedures to determine if a participant qualifies for the study was performed within 14 days prior to the start of treatment. Eligible participants who elected to enroll in the study then participated in a 28-day treatment period. Within the 28-day period, ataluren (PTC124) treatment was to be taken for 2 cycles of 14 days each 3 times per day with meals at a dose level of 5, 5, 10 milligrams/kilograms (mg/kg) in the first cycle and a dose level of 20, 20, 40 mg/kg in the second cycle. After the first 14-day cycle, study doses were changed to 10 mg/kg (morning), 10 mg/kg (midday), and 20 mg/kg (evening) and the doses were administered for 1 cycle only. Then, there was an interval of approximately 14 days without treatment. During the study, ataluren (PTC124) efficacy, safety, and pharmacokinetics were evaluated periodically with measurement of FVIII/FIX activity and inhibitor levels, other blood tests, and urinalysis.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Ability to provide written informed consent\n* Age ≥18 years\n* Presence of a nonsense mutation as the sole disease-causing mutation in the FVIII or FIX gene\n* At least 20 prior treatments with FVIII or FIX concentrates\n* Willingness and ability to comply with scheduled visits, drug administration plan, study restrictions, and study procedures\n\nExclusion Criteria:\n\n* Known hypersensitivity to any of the ingredients or excipients of the study drug\n* Any history of prior anti-FVIII/FIX inhibitors\n* Unable or unwilling to forego prophylactic FVIII/FIX concentrate use during the screening and on-study periods (Note: Participants were allowed use of FVIII/FIX concentrates for treatment of bleeding episodes while on study)'}, 'identificationModule': {'nctId': 'NCT00947193', 'briefTitle': 'Study of Ataluren (PTC124) in Hemophilia A and B', 'organization': {'class': 'INDUSTRY', 'fullName': 'PTC Therapeutics'}, 'officialTitle': 'A Phase 2a Study of Ataluren (PTC124) as an Oral Treatment for Nonsense-Mutation-Mediated Hemophilia A and B', 'orgStudyIdInfo': {'id': 'PTC124-GD-011-HEM'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ataluren Overall Study', 'description': "Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.", 'interventionNames': ['Drug: Ataluren']}], 'interventions': [{'name': 'Ataluren', 'type': 'DRUG', 'otherNames': ['PTC124'], 'description': 'Oral powder', 'armGroupLabels': ['Ataluren Overall Study']}]}, 'contactsLocationsModule': {'locations': [{'zip': '61614', 'city': 'Peoria', 'state': 'Illinois', 'country': 'United States', 'facility': 'The Bleeding and Clotting Disorders Institute', 'geoPoint': {'lat': 40.69365, 'lon': -89.58899}}, {'zip': '46260', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'St. Vincent Indianapolis Hospital', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '01605', 'city': 'Worcester', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'New England Hemophilia Center', 'geoPoint': {'lat': 42.26259, 'lon': -71.80229}}, {'zip': '45229', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': "Cincinnati Children's Hospital Medical Center", 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': "Children's Hospital of Philadelphia", 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt Hemostatis and Thrombosis Clinic', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '98104', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'Puget Sound Blood Center', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}, {'zip': 'V6Z 1Y6', 'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'facility': "St. Paul's Hospital", 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'city': 'Lille', 'country': 'France', 'facility': 'Hôpital Cardiologique', 'geoPoint': {'lat': 50.63391, 'lon': 3.05512}}, {'city': 'Lyon', 'country': 'France', 'facility': 'Hôpital Edouard Herriot', 'geoPoint': {'lat': 45.74906, 'lon': 4.84789}}, {'city': 'Paris', 'country': 'France', 'facility': 'Hôpital Necker Enfants Malades', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Florence', 'country': 'Italy', 'facility': 'Azienda Ospedaliero-Universitaria Careggi Viale G.B. Morgagni', 'geoPoint': {'lat': 43.77925, 'lon': 11.24626}}, {'city': 'Milan', 'country': 'Italy', 'facility': 'A.Bianchi Bonomi Hemophilia and Thrombosis Center', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}], 'overallOfficials': [{'name': 'Jay Barth, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'PTC Therapeutics'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'PTC Therapeutics', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Genzyme, a Sanofi Company', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}