Study of Ataluren (PTC124®) in Hemophilia A and B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00947193
Recruitment Status : Suspended
First Posted : July 27, 2009
Last Update Posted : November 1, 2011
Genzyme, a Sanofi Company
Information provided by:
PTC Therapeutics

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 patients 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 patients 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.

Condition or disease Intervention/treatment Phase
Hemophilia A Hemophilia B Drug: Ataluren (PTC124) Phase 2

Detailed Description:
In this study, patients with hemophilia A or hemophilia B due to a nonsense mutation will be treated with an investigational drug called ataluren (PTC124). Evaluation procedures to determine if a patient qualifies for the study will be performed within 14 days prior to the start of treatment. Eligible patients who elect to enroll in the study will then participate in a 28-day treatment period. Within the 28-day period, ataluren (PTC124) treatment will be taken 3 times per day with meals for 14 days at a dose of 10 mg/kg (morning), 10 mg/kg (midday) and 20 mg/kg (evening); there will then be an interval of approximately 14 days without treatment. During the study, ataluren (PTC124) efficacy, safety, and pharmacokinetics will be evaluated periodically with measurement of FVIII/FIX activity and inhibitor levels, other blood tests, and urinalysis.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a Study of Ataluren (PTC124) as an Oral Treatment for Nonsense-Mutation-Mediated Hemophilia A and B
Study Start Date : August 2009
Estimated Primary Completion Date : May 2012
Estimated Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Intervention Details:
  • Drug: Ataluren (PTC124)
    Ataluren (PTC124) will be provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren (PTC124) will be taken 3 times per day, with dosing based on the patient's body weight. The dose level for ataluren (PTC124) will be 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days.

Primary Outcome Measures :
  1. Pharmacological effect as measured by plasma FVIII/FIX activity [ Time Frame: 1.5 months ]

Secondary Outcome Measures :
  1. Effect of ataluren (PTC124) on additional markers of disease activity [ Time Frame: 1.5 months ]
  2. Safety profile of ataluren (PTC124) [ Time Frame: 1.5 months ]
  3. Compliance with ataluren (PTC124) administration [ Time Frame: 1.5 Months ]
  4. Ataluren (PTC124) plasma exposure [ Time Frame: 1.5 months ]
  5. Occurrence of bleeding episodes [ Time Frame: 1.5 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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: Patients are allowed use of FVIII/FIX concentrates for treatment of bleeding episodes while on study)

Information from the National Library of Medicine

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 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
Hôpital Cardiologique
Lille Cedex, France
Hôpital Edouard Herriot
Lyon Cedex, France
Hôpital Necker Enfants Malades
Paris, France
Azienda Ospedaliero-Universitaria Careggi Viale G.B. Morgagni
Firenze, Italy
A.Bianchi Bonomi Hemophilia and Thrombosis Center
Milano, Italy
Sponsors and Collaborators
PTC Therapeutics
Genzyme, a Sanofi Company
Principal Investigator: Jay Barth, MD PTC Therapeutics

Additional Information:
Responsible Party: Peter Riebling, PTC Therapeutics Identifier: NCT00947193     History of Changes
Other Study ID Numbers: PTC124-GD-011-HEM
First Posted: July 27, 2009    Key Record Dates
Last Update Posted: November 1, 2011
Last Verified: October 2011

Keywords provided by PTC Therapeutics:
Hemophilia A
Hemophilia B
Factor VIII
Factor IX
Nonsense mutation
Premature stop codon

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Factor VIII