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

NCT00847379 | Terminated Phase 2 Results DMC

• 1 other identifier: PTC124-GD-007e-DMD
• Study Type: interventional
• Target: 173
• Locations: 11 countries
• Sites: 37

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.

Conditions

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; Becker muscular dystrophy; Nonsense mutation; Premature stop codon; DMD; BMD; Ataluren; PTC124

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (AEs)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function) and severe (interferes significantly with usual function). Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Baseline (Week 48 of Study 007) up to Week 102

• Number of Participants With Clinically Significant Abnormal Laboratory Parameters

  Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement.

  Baseline (Week 48 of Study 007) up to Week 102

Secondary Outcomes (21)

• Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60

  Baseline (Week 48 of Study 007), Week 60

• Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM)

  Baseline (Week 48 of Study 007), Week 60

• Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM

  Baseline (Week 48 of Study 007), Week 60

• Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM

  Baseline (Week 48 of Study 007), Week 60

• Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM

  Baseline (Week 48 of Study 007), Week 60

Study Arms (1)

Overall Participants: High-Dose Ataluren

EXPERIMENTAL

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.

Drug: Ataluren

Interventions

Ataluren DRUG

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

Also known as: PTC124

Overall Participants: High-Dose Ataluren

Eligibility Criteria

• Age: 5 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (37)

University of California - Davis

Sacramento, California, 95817, United States

Location

Department of Rehabilitation, The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Child Neurology Center of NW Florida

Gulf Breeze, Florida, 32561, United States

Location

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

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Children's Hospital of Boston

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Shriners Hospital for Children-Portland

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Southwestern University

Dallas, Texas, 75207, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

The Children's Hospital at Westmead

Westmead, 2145, Australia

Location

UZ Leuven

Leuven, Belgium

Location

Alberta Children's Hospital

London, Ontario, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, Canada

Location

British Colombia Children's Hopsital

Vancouver, Canada

Location

Hopital d'Enfants CHU Timone

Marseille, 13385, France

Location

Laboratoire d'Exploration Fonctionnelles

Nantes, France

Location

Groupe Hospitalier Pitie-Salpetriere, Institut de Myologie

Paris, France

Location

University of Essen - Clinic for Children

Essen, Germany

Location

University Hospital

Freiburg im Breisgau, Germany

Location

Hadassah University Hopspital

Jerusalem, Israel

Location

Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Milan, 20122, Italy

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

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

Roma, 00168, Italy

Location

Hospital Sant Joan de Deu

Barcelona, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

Queen Silvia Children's Hospital

Gothenburg, S-416 85, Sweden

Location

Astrid Lindgren Pediatric Hospital

Stockholm, Sweden

Location

UCL Instititute of Child Health, Dubowitz

London, United Kingdom

Location

University of Newcastle

Newcastle upon Tyne, United Kingdom

Location

Robert Jones & Agnes Hunt Orthopaedic Hospital

Oswestry, United Kingdom

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

• Sponsor's web site

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

ataluren

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

This study was prematurely terminated by Sponsor per Data Monitoring Committee (DMC) recommendation to discontinue ongoing studies of high-dose ataluren in nmDBMD due to lack of efficacy for the high-dose ataluren.

Results Point of Contact

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

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Leone Atkinson, M.D., Ph.D.

  PTC Therapeutics

  STUDY DIRECTOR

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: February 16, 2009
• First Posted: February 19, 2009
• Study Start: January 31, 2009
• Primary Completion: May 24, 2010
• Study Completion: May 24, 2010
• Last Updated: July 15, 2020
• Results First Posted: July 15, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); AU (2); IT (3); BE (1); SE (2); US (15); IL (1); CA (3); ES (2); GB (3); DE (2)