Study of Ataluren (PTC124®) in Hemophilia A and B - Full Text View

Purpose

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	Intervention	Phase
Hemophilia A Hemophilia B	Drug: Ataluren (PTC124)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia

MedlinePlus related topics: Bleeding Disorders Hemophilia

U.S. FDA Resources

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:

Pharmacological effect as measured by plasma FVIII/FIX activity [ Time Frame: 1.5 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Effect of ataluren (PTC124) on additional markers of disease activity [ Time Frame: 1.5 months ] [ Designated as safety issue: No ]
Safety profile of ataluren (PTC124) [ Time Frame: 1.5 months ] [ Designated as safety issue: Yes ]
Compliance with ataluren (PTC124) administration [ Time Frame: 1.5 Months ] [ Designated as safety issue: No ]
Ataluren (PTC124) plasma exposure [ Time Frame: 1.5 months ] [ Designated as safety issue: No ]
Occurrence of bleeding episodes [ Time Frame: 1.5 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	August 2009
Estimated Study Completion Date:	May 2012
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00947193

Locations

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
France
Hôpital Cardiologique
Lille Cedex, France
Hôpital Edouard Herriot
Lyon Cedex, France
Hôpital Necker Enfants Malades
Paris, France
Italy
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

Investigators

Principal Investigator:

Jay Barth, MD

PTC Therapeutics

More Information

Additional Information:

PTC Therapeutic's website This link exits the ClinicalTrials.gov site

Publications:

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.

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. Epub 2007 Apr 22.

Responsible Party:	Peter Riebling, PTC Therapeutics
ClinicalTrials.gov Identifier:	NCT00947193 History of Changes
Other Study ID Numbers:	PTC124-GD-011-HEM
Study First Received:	July 23, 2009
Last Updated:	October 31, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by PTC Therapeutics:

Hemophilia A
Hemophilia B
Factor VIII
Factor IX
FVIII
FIX

Nonsense mutation
Premature stop codon
HA
HB
PTC124
Ataluren

Additional relevant MeSH terms:

Hemophilia B
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders

Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013