Study of Ataluren (PTC124) in Hemophilia A and B

NCT00947193 | Terminated Phase 2 Results

• 1 other identifier: PTC124-GD-011-HEM
• Study Type: interventional
• Target: 13
• Locations: 4 countries
• Sites: 13

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.

Conditions

Hemophilia A; Hemophilia B

Keywords

Hemophilia A; Hemophilia B; Factor VIII; Factor IX; FVIII; FIX; Nonsense mutation; Premature stop codon; HA; HB; PTC124; Ataluren

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Plasma FVIII/FIX Activity Response at Day 14

  A plasma FVIII/FIX activity response was defined as an end-of-treatment (Day 14) activity of ≥1%.

  Baseline up to Day 14

Secondary Outcomes (6)

• Number of Participants With a Change From Baseline in Plasma Anti-FVIII/FIX Inhibitor Titers at Day 14

  Baseline and Day 14

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug

  Baseline up to Day 28

• Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters

  Baseline up to Day 28

• Compliance With Ataluren Administration

  Baseline up to Day 28

• Ataluren Plasma Exposure

  Day 10 (pre-dose) and Day 14 (post-dose)

Study Arms (1)

Ataluren Overall Study

EXPERIMENTAL

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.

Drug: Ataluren

Interventions

Ataluren DRUG

Oral powder

Also known as: PTC124

Ataluren Overall Study

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• PTC Therapeutics: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (13)

The Bleeding and Clotting Disorders Institute

Peoria, Illinois, 61614, United States

Location

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

New England Hemophilia Center

Worcester, Massachusetts, 01605, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Hemostatis and Thrombosis Clinic

Nashville, Tennessee, 37232, United States

Location

Puget Sound Blood Center

Seattle, Washington, 98104, United States

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Hôpital Cardiologique

Lille, France

Location

Hôpital Edouard Herriot

Lyon, France

Location

Hôpital Necker Enfants Malades

Paris, France

Location

Azienda Ospedaliero-Universitaria Careggi Viale G.B. Morgagni

Florence, Italy

Location

A.Bianchi Bonomi Hemophilia and Thrombosis Center

Milan, Italy

Location

Related Publications (2)

• 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.

  PMID: 17389552 BACKGROUND

• 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.

  PMID: 17450125 BACKGROUND

Related Links

• PTC Therapeutics' website

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Interventions

ataluren

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Jay Barth, MD

  PTC Therapeutics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: July 27, 2009
• Study Start: October 14, 2009
• Primary Completion: August 30, 2011
• Study Completion: August 30, 2011
• Last Updated: June 16, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-05

Locations

IT (2); CA (1); FR (3); US (7)