Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD)

NCT00759876 | Terminated Phase 2 Results

• 1 other identifier: PTC124-GD-004e-DMD
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

Duchenne muscular dystrophy (DMD) 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 in approximately 10-15% of boys with the disease. Ataluren is an orally-delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a extension trial that will evaluate the long-term safety of ataluren in boys with nonsense mutation DMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, strength, and other important clinical and laboratory measures.

Conditions

Duchenne Muscular Dystrophy

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  TEAE: any untoward medical occurrence or undesirable event(s) that begins or worsens following administration of the study drug, whether or not considered related to the treatment by the Investigator. Severity of an adverse event (AE) was classified as: mild (does not interfere with usual function), moderate (interferes with usual function; may require medical intervention), severe (interferes significantly with usual function; likely require medical intervention), life-threatening, and fatal. 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. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Baseline up to Week 89

Secondary Outcomes (18)

• Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)

  Baseline, Week 48 and Week 60

• Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests

  Baseline, Week 48 and Week 60

• Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests

  Baseline, Week 48 and Week 60

• Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests

  Baseline, Week 48 and Week 60

• Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests

  Baseline, Week 48 and Week 60

Study Arms (1)

Ataluren

EXPERIMENTAL

Participants will receive ataluren 3 times per day with meals at doses of 20 milligrams per kilogram (mg/kg) (breakfast), 20 mg/kg (lunch), and 40 mg/kg (dinner) for up to 89 weeks.

Drug: Ataluren

Interventions

Ataluren DRUG

Ataluren will be provided as a vanilla-flavored powder to be mixed with milk. Dosing based on participant body weight

Also known as: PTC124

Ataluren

Eligibility Criteria

• Gender Eligibility Details: Male participants only are being studied.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of ataluren treatment in the previous Phase 2a study (Protocol PTC124-GD-004-DMD).
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age).
• Confirmed screening laboratory values within the central laboratory ranges.
• In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren 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:

• Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
• Treatment with warfarin within 1 month prior to start of study treatment.
• 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 \[colloidal silica\], and magnesium stearate).
• Exposure to another investigational drug within 2 months prior to start of study treatment.
• History of major surgical procedure within 1 month prior to start of study treatment.
• Ongoing immunosuppressive therapy (other than corticosteroids).
• Ongoing participation in any other clinical trial (except for sub-studies specifically approved by PTC Therapeutics).
• Clinically significant symptoms and signs of congestive heart failure (CHF) (American College of Cardiology/American Heart Association Stage C or Stage D).
• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, 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 (3)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

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

• Related Info

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

Results Point of Contact

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

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Leone Atkinson

  PTC Therapeutics, Inc.

  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: September 23, 2008
• First Posted: September 25, 2008
• Study Start: August 13, 2008
• Primary Completion: May 17, 2010
• Study Completion: May 17, 2010
• Last Updated: October 29, 2020
• Results First Posted: October 29, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)