Phase 2B Extension Study of Ataluren (PTC124) in Duchenne/Becker Muscular Dystrophy (DMD/BMD)

NCT ID: NCT00847379

Last Updated: 2020-07-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2010-05-24

Brief Summary

Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b extension trial that will evaluate the long-term safety of ataluren (PTC124) in boys with nonsense mutation DMD/BMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, and other important clinical and laboratory measures.

Detailed Description

This is a Phase 2b, international, multicenter, open-label extension study for participants who successfully completed blinded study drug in Study 007. This extension study will evaluate the long-term administration of ataluren administered 3 times per day (TID) at morning, midday, and evening doses of 20, 20, and 40 milligrams/kilogram (mg/kg), respectively, in participants with nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD).

Conditions

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy

Study Design

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

Study Groups

Overall Participants: High-Dose Ataluren

All participants will receive ataluren suspension orally three times a day (TID), 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, will be initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose will be increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level is well tolerated.

Group Type: EXPERIMENTAL

Ataluren

Intervention Type: DRUG

Ataluren oral powder for suspension will be administered as per dose and schedule specified in the arm.

Interventions

Ataluren

Ataluren oral powder for suspension will be administered as per dose and schedule specified in the arm.

Intervention Type: DRUG

Other Intervention Names

PTC124

Eligibility Criteria

Inclusion Criteria

• Completion of blinded study drug treatment in the previous Phase 2b study (PTC124-GD-007-DMD).
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if less than [<]18 years of age).
• In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during PTC124 administration and the 6-week follow up period.
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria

• Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
• Ongoing participation in any other therapeutic clinical trial.
• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.

• Minimum Eligible Age: 5 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

Leone Atkinson, M.D., Ph.D.

Role: STUDY_DIRECTOR

PTC Therapeutics

Locations

University of California - Davis

Sacramento, California, United States

Department of Rehabilitation, The Children's Hospital

Aurora, Colorado, United States

Child Neurology Center of NW Florida

Gulf Breeze, Florida, United States

University of Iowa Children's Hospital, Division of Child Neurology

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Children's Hospital of Boston

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University Medical School

St Louis, Missouri, United States

Columbia University

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Shriners Hospital for Children-Portland

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Southwestern University

Dallas, Texas, United States

University of Utah

Salt Lake City, Utah, United States

The Royal Children's Hospital

Parkville, Victoria, Australia

The Children's Hospital at Westmead

Westmead, , Australia

UZ Leuven

Leuven, , Belgium

Alberta Children's Hospital

London, Ontario, Canada

Children's Hospital of Western Ontario

London, Ontario, Canada

British Colombia Children's Hopsital

Vancouver, , Canada

Hopital d'Enfants CHU Timone

Marseille, , France

Laboratoire d'Exploration Fonctionnelles

Nantes, , France

Groupe Hospitalier Pitie-Salpetriere, Institut de Myologie

Paris, , France

University of Essen - Clinic for Children

Essen, , Germany

University Hospital

Freiburg im Breisgau, , Germany

Hadassah University Hopspital

Jerusalem, , Israel

Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Milan, , Italy

Ospedale Pediatrico Bambino Gesu

Roma, , Italy

U.O. Complessa di Neuropsichiatria Infantile-Policlinico A. Gemelli-Universita Cattolica

Roma, , Italy

Hospital Sant Joan de Deu

Barcelona, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Queen Silvia Children's Hospital

Gothenburg, , Sweden

Astrid Lindgren Pediatric Hospital

Stockholm, , Sweden

UCL Instititute of Child Health, Dubowitz

London, , United Kingdom

University of Newcastle

Newcastle upon Tyne, , United Kingdom

Robert Jones & Agnes Hunt Orthopaedic Hospital

Oswestry, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Israel; Italy; Spain; Sweden; United Kingdom

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

Sponsor's web site

Other Identifiers

PTC124-GD-007e-DMD

Identifier Type: -

Identifier Source: org_study_id