Safety and Efficacy Study of PTC124 in Duchenne Muscular Dystrophy

NCT00264888 | Completed Phase 2

• 1 other identifier: PTC124-GD-004-DMD
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief Summary

In some patients with Duchenne muscular dystrophy (DMD), the disease is caused by a nonsense mutation (premature stop codon) in the gene that makes the dystrophin protein. PTC124 has been shown to partially restore dystrophin production in animals with DMD due to a nonsense mutation. The main purpose of this study is to understand whether PTC124 can safely increase functional dystrophin protein in the muscles of patients with DMD due to a nonsense mutation.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; Nonsense mutation; Premature stop codon

Outcome Measures

Primary Outcomes (1)

• Dystrophin expression as assessed by immunofluorescence evaluation of tissue obtained by biopsy of the extensor digitorum brevis (EDB) muscle of the foot or tibialis anterior (TA) muscle of the leg

Secondary Outcomes (1)

• Presence of dystrophin mRNA and dystrophin-related proteins on EDB or TA muscle biopsy, muscle function, compliance with treatment, safety and PTC124 pharmacokinetics

Interventions

PTC124 DRUG

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:

• Diagnosis of DMD based on a clinical phenotype presenting by age 5, with increased serum CK and decrease of dystrophin on a muscle biopsy
• Presence of a nonsense mutation in the dystrophin gene
• Physical examination or radiographic imaging documenting the presence of EDB or TA muscles in both legs
• Ability to ambulate, or if non-ambulatory, then not requiring ventilator support
• Male sex
• Age ≥ 5 years
• Willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and follow-up periods in subjects known to be sexually active
• Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and study procedures (including muscle biopsies, myometry, and PK sampling)
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age)

You may not qualify if:

• Prior or ongoing medical condition (e.g., concomitant illness, psychiatric condition, 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
• Clinical symptoms and signs of congestive cardiac failure
• Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test
• Hemoglobin \<10 g/dL
• Serum albumin \<2.5 g/dL
• Abnormal GGT or total bilirubin (\>laboratory's upper limit of normal)
• Abnormal renal function (serum creatinine \>1.5 times laboratory's upper limit of normal)
• History of solid organ or hematological transplantation
• Ongoing immunosuppressive therapy (other than corticosteroids)
• Exposure to another investigational drug within 28 days prior to start of study treatment
• Ongoing participation in any other therapeutic clinical trial
• Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma (PPAR γ) agonists, e.g., rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent)
• Change in systemic corticosteroid therapy (e.g., initiation of treatment; cessation of treatment; change in dose, schedule, or type of steroid) within 3 months prior to start of study treatment.
• Treatment with systemic aminoglycoside antibiotics within 4 weeks prior to start of study treatment

Sponsors & Collaborators

• PTC Therapeutics: lead
• Muscular Dystrophy Association: collaborator

Study Sites (3)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4399, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Finkel RS, Flanigan KM, Wong B, Bonnemann C, Sampson J, Sweeney HL, Reha A, Northcutt VJ, Elfring G, Barth J, Peltz SW. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS One. 2013 Dec 11;8(12):e81302. doi: 10.1371/journal.pone.0081302. eCollection 2013.

  PMID: 24349052 DERIVED

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

Study Officials

• Richard Finkel, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 9, 2005
• First Posted: December 13, 2005
• Study Start: December 1, 2005
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: January 14, 2009

Record last verified: 2009-01

Locations

US (3)