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Phase 2b Study of PTC124 in Duchenne/Becker Muscular Dystrophy (DMD/BMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00592553
Recruitment Status : Completed
First Posted : January 14, 2008
Last Update Posted : December 8, 2017
Information provided by (Responsible Party):
PTC Therapeutics

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. 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 trial that will evaluate the clinical benefit of PTC124 in boys with DMD/BMD due to a nonsense mutation. The main goals of the study are to understand whether PTC124 can improve walking, activity, muscle function, and strength and whether the drug can safely be given for a long period of time.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Becker Muscular Dystrophy Drug: PTC124 High Dose Drug: PTC124 Low Dose Drug: Placebo Phase 2

Detailed Description:
This study is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, efficacy and safety study, designed to document the clinical benefit of PTC124 when administered as therapy of patients with DMD/BMD due to a nonsense mutation (premature stop codon) in the dystrophin gene. It is planned that ~165 boys who are at least 5 years of age and can walk at least 75 meters (80 yards) will be enrolled. Study subjects will be enrolled at sites in North America, Europe, Israel, and Australia. They will be randomized in a 1:1:1 ratio to either a higher dose of PTC124, a lower dose of PTC124, or placebo. Subjects will receive study drug 3 times per day (at breakfast, lunch, and dinner) for 48 weeks. Subjects will be evaluated at clinic visits every 6 weeks. Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 3 weeks for the first 24 weeks of the study. At the completion of blinded treatment, all compliant participants will be eligible to receive open-label PTC124 in a separate extension study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b Efficacy and Safety Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
Actual Study Start Date : February 2008
Actual Primary Completion Date : December 2009
Actual Study Completion Date : December 2009

Arm Intervention/treatment
Active Comparator: PTC124 High Dose
PTC124 - 20-, 20-, 40-mg/kg dose level (high-dose PTC124) for 48 weeks.
Drug: PTC124 High Dose
PTC124 High Dose - 20-, 20-, 40-mg/kg dose level

Active Comparator: PTC124 Low Dose
PTC124 - 10-, 10-, 20 mg/kg dose level (low-dose PTC124) for 48 weeks.
Drug: PTC124 Low Dose
PTC124 Low Dose - 10-, 10-, 20 mg/kg dose level

Placebo Comparator: Placebo
Placebo PO TID for 48 weeks.
Drug: Placebo

Primary Outcome Measures :
  1. To determine the effect of PTC124 on ambulation in subjects with nonsense-mutation-mediated DMD/BMD (as assessed by changes in the distance walked during a 6-minute walk test) [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Activity in the community setting [ Time Frame: 12 months ]
  2. Proximal muscle function [ Time Frame: 12 months ]
  3. Muscle strength [ Time Frame: 12 months ]
  4. Muscle fragility [ Time Frame: 12 months ]
  5. Biceps muscle dystrophin expression [ Time Frame: 12 months ]
  6. Quality of Life [ Time Frame: 12 months ]
  7. Cognitive ability [ Time Frame: 12 months ]
  8. Cardiac function [ Time Frame: 12 months ]
  9. Frequency of accidental falls during ambulation [ Time Frame: 12 Months ]
  10. Treatment satisfaction [ Time Frame: 12 Months ]
  11. Safety [ Time Frame: 12 months ]
  12. Compliance with treatment [ Time Frame: 12 months ]
  13. PTC124 pharmacokinetics [ Time Frame: 12 months ]

Other Outcome Measures:
  1. Dystrophin Expression [ Time Frame: 12 Months ]
    Change in biceps muscle dystrophin expression as determined by immunofluorescence

  2. Cardiac Function [ Time Frame: 12 Months ]
    Change in heart rate before, during and after each 6WMT as assessed by Polar RS400 heart rate monitor

  3. Accidental falling during ambulation [ Time Frame: 12 Months ]
    Frequency of accidental falls during ambulation as recorded by subjects and/or parent/caregivers in a daily diary

  4. Parent/caregiver-reported treatment satisfaction [ Time Frame: 12 Months ]
    Change in treatment satisfaction as measured by the TSQM

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age)
  • Male sex.
  • Age ≥5 years.
  • Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs (ie., proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking.
  • Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.
  • Ability to walk ≥75 meters unassisted during the screening 6-minute walk test.
  • Documentation that a baseline renal ultrasound has been performed.
  • Confirmed screening laboratory values within the central laboratory ranges (adrenal, renal, and serum electrolytes parameters)
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

  • Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
  • Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or change in systemic corticosteroid therapy (eg, initiation, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, or reinitiation) within 3 months prior to start of study treatment.
  • Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure within 3 months prior to start of study treatment.
  • Treatment with warfarin within 1 month prior to start of study treatment.
  • Prior therapy with PTC124.
  • 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).
  • Exposure to another investigational drug within 2 months prior to start of study treatment.
  • History of major surgical procedure within 30 days prior to start of study treatment.
  • Ongoing immunosuppressive therapy (other than corticosteroids).
  • Ongoing participation in any other therapeutic clinical trial.
  • Expectation of major surgical procedure (eg, scoliosis surgery) during the 12 month treatment period of the study.
  • Requirement for daytime ventilator assistance.
  • Clinical symptoms and signs of congestive heart failure (American College of Cardiology/American Heart Association Stage C or Stage D) or evidence on echocardiogram of clinically significant myopathy
  • Prior or ongoing medical condition (eg, 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 subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00592553

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Sponsors and Collaborators
PTC Therapeutics
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Study Director: Leone Atkinson, MD, PhD PTC Therapeutics

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Responsible Party: PTC Therapeutics Identifier: NCT00592553    
Other Study ID Numbers: PTC124-GD-007-DMD
First Posted: January 14, 2008    Key Record Dates
Last Update Posted: December 8, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by PTC Therapeutics:
Duchenne muscular dystrophy
Becker muscular dystrophy
Nonsense mutation
Premature stop codon
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked