Study of Ataluren (PTC124) in Hemophilia A and B

NCT ID: NCT00947193

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-14
• Study Completion Date: 2011-08-30

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.

Conditions

Hemophilia A; Hemophilia B

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ataluren

Intervention Type: DRUG

Oral powder

Interventions

Ataluren

Oral powder

Intervention Type: DRUG

Other Intervention Names

PTC124

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

PTC Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jay Barth, MD

Role: PRINCIPAL_INVESTIGATOR

PTC Therapeutics

Locations

The Bleeding and Clotting Disorders Institute

Peoria, Illinois, United States

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

New England Hemophilia Center

Worcester, Massachusetts, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Vanderbilt Hemostatis and Thrombosis Clinic

Nashville, Tennessee, United States

Puget Sound Blood Center

Seattle, Washington, United States

St. Paul's Hospital

Vancouver, British Columbia, Canada

Hôpital Cardiologique

Lille, , France

Hôpital Edouard Herriot

Lyon, , France

Hôpital Necker Enfants Malades

Paris, , France

Azienda Ospedaliero-Universitaria Careggi Viale G.B. Morgagni

Florence, , Italy

A.Bianchi Bonomi Hemophilia and Thrombosis Center

Milan, , Italy

Countries

United States; Canada; France; Italy

References

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.

Reference Type: BACKGROUND

PMID: 17389552 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17450125 (View on PubMed)

Related Links

http://www.ptcbio.com

PTC Therapeutics' website

Other Identifiers

PTC124-GD-011-HEM

Identifier Type: -

Identifier Source: org_study_id