Trial record 5 of 116 for:    "muscular dystrophy, duchenne and becker types"

Study of Ataluren (PTC124®) in Nonambulatory Patients With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)

This study has been terminated.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
PTC Therapeutics
ClinicalTrials.gov Identifier:
NCT01009294
First received: November 5, 2009
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

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 2a trial that will enroll boys with nonsense mutation DMD/BMD who have lost independent mobility due to the disease. This study will evaluate the safety and tolerability of ataluren (PTC124) and will also evaluate efficacy outcomes in this patient population.


Condition Intervention Phase
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Drug: Ataluren (PTC124)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2a Study of Ataluren (PTC124) in Nonambulatory Patients With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:
  • Safety and tolerability of ataluren (PTC124) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Upper extremity function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Upper extremity range of motion [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Upper extremity muscle strength [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Hand fine-motor coordination and dexterity [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Pulmonary function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Cardiac function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Cognitive ability [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Health-related quality of life [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Activities of daily living [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Muscle fragility as determined by serum CK levels [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Muscle dystrophin expression [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Ataluren compliance [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Ataluren plasma exposure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: November 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ataluren (PTC124) Drug: Ataluren (PTC124)
Oral powder for suspension taken 3 times per day (20 mg/kg with breakfast, 20 mg/kg with lunch, and 40 mg/kg with dinner) for up to 48 weeks.

Detailed Description:

It is planned that this Phase 2a, open-label, safety and efficacy study will be performed at 5 sites in the US and 1 site in the UK.

The study will enroll ~30 boys with nonsense mutation DMD/BMD who have been nonambulatory for at least one year. Enrollment will be stratified to ensure evaluation of ~15 participants who are receiving chronic corticosteroid therapy and of ~15 participants who are not receiving chronic corticosteroid therapy. Subjects will take ataluren 3 times per day (at breakfast, lunch, and dinner) for 48 weeks (~1 year). Study assessments will be performed at clinic visits during screening, every 6 weeks for 2 visits and then every 12 weeks until the end of the study. Additional safety laboratory testing is required 4 times during the course of the study; this may be performed at the investigational site, at an accredited local laboratory or clinic, or in the subject's home using a nursing service.

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of DMD or BMD
  • Presence of a nonsense mutation in the dystrophin gene
  • Unable to ambulate independently for ≥1 year due to DMD/BMD
  • Presence of sufficient shoulder and elbow function to perform study-related functional procedures (eg, 9-hole peg test)
  • Adequate hepatic, renal, and adrenal function
  • Ability to provide evaluable pretreatment echocardiogram and lung function assessments
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age)

Exclusion Criteria:

  • Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or change in systemic corticosteroid therapy within 3 months prior to start of study treatment
  • Use of any intermittent systemic corticosteroid therapy regimen (eg, 10 days on followed by 10 days off, weekend dosing, every-other-day dosing); note that patients must either be receiving a daily dosing regimen of prednisone, prednisolone, or deflazacort at the time of enrollment into the study or must not be receiving any systemic corticosteroids
  • Any change in treatment for congestive heart failure within 3 months prior to start of study treatment
  • Ongoing warfarin or phenytoin therapy
  • Prior therapy with ataluren
  • Known hypersensitivity to any of the ingredients or excipients of ataluren (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 1 month prior to start of study treatment or expectation of major surgical procedure (eg, scoliosis surgery) during the 48-week treatment period of the study
  • Ongoing immunosuppressive therapy (other than corticosteroids)
  • Ongoing participation in any other clinical trial
  • Requirement for daytime ventilator assistance
  • Uncontrolled clinical symptoms and signs of congestive heart failure
  • Prior or ongoing medical condition (eg, 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01009294

Locations
United States, California
University of California-Davis
Davis, California, United States, 95616
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University Medical School
St. Louis, Missouri, United States, 63110
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United Kingdom
University of Newcastle
Newcastle upon Tyne, United Kingdom, NE1 3BZ
Sponsors and Collaborators
PTC Therapeutics
Genzyme, a Sanofi Company
Investigators
Study Director: Leone Atkinson, MD, PhD PTC Therapeutics
  More Information

Additional Information:
No publications provided

Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT01009294     History of Changes
Other Study ID Numbers: PTC124-GD-008-DMD
Study First Received: November 5, 2009
Last Updated: August 28, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by PTC Therapeutics:
Duchenne muscular dystrophy
Becker muscular dystrophy
Nonsense mutation
Premature stop codon
DMD
BMD
Ataluren
PTC124

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on April 17, 2014