Study of Ataluren (PTC124) in Hemophilia A and B
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|ClinicalTrials.gov Identifier: NCT00947193|
Recruitment Status : Terminated (Study was terminated early due to Sponsor decision and not reflective of adverse safety findings.)
First Posted : July 27, 2009
Results First Posted : June 16, 2020
Last Update Posted : June 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hemophilia A Hemophilia B||Drug: Ataluren||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2a Study of Ataluren (PTC124) as an Oral Treatment for Nonsense-Mutation-Mediated Hemophilia A and B|
|Actual Study Start Date :||October 14, 2009|
|Actual Primary Completion Date :||August 30, 2011|
|Actual Study Completion Date :||August 30, 2011|
Experimental: Ataluren Overall Study
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.
Other Name: PTC124
- Number of Participants With a Plasma FVIII/FIX Activity Response at Day 14 [ Time Frame: Baseline up to Day 14 ]A plasma FVIII/FIX activity response was defined as an end-of-treatment (Day 14) activity of ≥1%.
- Number of Participants With a Change From Baseline in Plasma Anti-FVIII/FIX Inhibitor Titers at Day 14 [ Time Frame: Baseline and Day 14 ]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).
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug [ Time Frame: Baseline up to Day 28 ]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.
- Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters [ Time Frame: Baseline up to Day 28 ]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.
- Compliance With Ataluren Administration [ Time Frame: Baseline up to Day 28 ]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.
- Ataluren Plasma Exposure [ Time Frame: Day 10 (pre-dose) and Day 14 (post-dose) ]The ataluren plasma concentrations before and 2 hours after the first morning dose at end of treatment was measured.
- Occurrence of Bleeding Episodes [ Time Frame: Baseline up to Day 28 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00947193
|United States, Illinois|
|The Bleeding and Clotting Disorders Institute|
|Peoria, Illinois, United States, 61614|
|United States, Indiana|
|St. Vincent Indianapolis Hospital|
|Indianapolis, Indiana, United States, 46260|
|United States, Massachusetts|
|New England Hemophilia Center|
|Worcester, Massachusetts, United States, 01605|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Tennessee|
|Vanderbilt Hemostatis and Thrombosis Clinic|
|Nashville, Tennessee, United States, 37232|
|United States, Washington|
|Puget Sound Blood Center|
|Seattle, Washington, United States, 98104|
|Canada, British Columbia|
|St. Paul's Hospital|
|Vancouver, British Columbia, Canada, V6Z 1Y6|
|Lille Cedex, France|
|Hôpital Edouard Herriot|
|Lyon Cedex, France|
|Hôpital Necker Enfants Malades|
|Azienda Ospedaliero-Universitaria Careggi Viale G.B. Morgagni|
|A.Bianchi Bonomi Hemophilia and Thrombosis Center|
|Principal Investigator:||Jay Barth, MD||PTC Therapeutics|