Brief Title
Study of Ataluren (PTC124) in Hemophilia A and B
Official Title
A Phase 2a Study of Ataluren (PTC124) as an Oral Treatment for Nonsense-Mutation-Mediated Hemophilia A and B
Brief Summary
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.
Detailed Description
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants With a Plasma FVIII/FIX Activity Response at Day 14
Secondary Outcome
Number of Participants With a Change From Baseline in Plasma Anti-FVIII/FIX Inhibitor Titers at Day 14
Condition
Hemophilia A
Intervention
Ataluren
Study Arms / Comparison Groups
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
13
Start Date
October 14, 2009
Completion Date
August 30, 2011
Primary Completion Date
August 30, 2011
Eligibility Criteria
Inclusion Criteria:
- Ability to provide written informed consent
- Age ≥18 years
- Presence of a nonsense mutation as the sole disease-causing mutation in the FVIII or
FIX gene
- At least 20 prior treatments with FVIII or FIX concentrates
- Willingness and ability to comply with scheduled visits, drug administration plan,
study restrictions, and study procedures
Exclusion Criteria:
- Known hypersensitivity to any of the ingredients or excipients of the study drug
- Any history of prior anti-FVIII/FIX inhibitors
- 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)
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Jay Barth, MD, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00947193
Organization ID
PTC124-GD-011-HEM
Responsible Party
Sponsor
Study Sponsor
PTC Therapeutics
Collaborators
Genzyme, a Sanofi Company
Study Sponsor
Jay Barth, MD, Principal Investigator, PTC Therapeutics
Verification Date
May 2020