A Study of Experimental Medicine Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

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"Volunteer for research at UC Davis and contribute to discoveries that may improve health care for you, your family, and your community!"
Age: 7 to 16 years old
Gender:
Male
Healthy Volunteers: No
Keywords: Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases
Type: Drug study, Phase 3
Target:
10 Participants
Investigator:
Description
Your child is being asked to take part in a research study because he has Duchenne muscular dystrophy (DMD).

DMD is caused by a mutation (or error) in the gene for dystrophin. Dystrophin is a protein that keeps muscles healthy by maintaining structure of muscle cells. One type of mutation in the dystrophin gene is called a nonsense mutation. This type of mutation is the cause of DMD in about 15% of boys with the disease. A nonsense mutation in the dystrophin gene causes a premature stop signal. This premature stop signal tells the body’s protein production machinery to stop making the dystrophin protein in muscle before the protein is complete. The result is a shortened dystrophin protein that does not work and weakens muscles.

Your child is being offered an opportunity to take part in this research study because he has DMD caused by a nonsense mutation in the dystrophin gene and has recently completed the PTC124-GD-020-DMD study.

This study is an extension of the PTC124-GD-020-DMD study. The main goal of this study is to better understand whether experimental medicine ataluren can be safely given for a long period of time. The study will also provide additional information as to whether the actions of ataluren can result in improved walking, activity, muscle function, muscle fragility, upper limb function, pulmonary function, health-related quality of life (via PODCI) in boys with DMD.

This research study will test an investigational drug called ‘ataluren’. The regulatory authorities have permitted use of ataluren in this study as part of a process to find out if it could one day be made more widely available for doctors to prescribe it for patients with DMD.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent per local requirements.
  • Male sex.
  • Age ≥7 and ≤16 years.
  • Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (eg. proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 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.
  • Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
  • Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
  • Ability to walk ≥150 meters unassisted during the screening 6-minute walk test. Patients need to be below the protocol-specified threshold for %-predicted 6MWD.
  • Results of the 2 Baseline 6MWD results must be determined as valid and results of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.
  • Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20% reduction from the valid Screening 6MWD.
  • Confirmed screening laboratory values within the central laboratory ranges (hepatic, renal, and serum electrolyte parameters)
  • Willingness to abstain from sexual intercourse or employ an approved method of contraception during the period of study drug administration and 6-week follow-up period.
  • 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 corticosteroids therapy within 6 months prior to start of study treatment.
  • Change in systemic corticosteroid therapy (eg, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, 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 (CHF) within 3 months prior to start of study treatment.
  • Ongoing use of coumarin-based anticoagulants (eg. warfarin), phenytoin, tolbutamide, or paclitaxel.
  • Prior therapy with ataluren.
  • Known hypersensitivity to any of the ingredients or excipients of the study drug
  • Exposure to another investigational drug within 3 months prior to start of study treatment.
  • History of major surgical procedure within 6 weeks prior to start of study treatment.
  • Ongoing immunosuppressive therapy (other than corticosteroids).
  • Ongoing participation in any clinical trial (except for studies specifically approved by PTC Therapeutics).
  • Expectation of major surgical procedure (eg, scoliosis surgery) during the 12-month treatment period of the study.
  • Requirement for daytime ventilator assistance. Note: Evening ventilator assistance and use of bi-level positive airway pressure (Bi-PAP) therapy is allowed.
  • Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D).
  • Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings (eg. lower limb injury that may affect 6MWT performance), 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.
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
We expect that you will be in this research study for about 144 weeks (~3 years) including 10 visits to UC Davis.
Recruitment period
From April 28, 2014
Location
UC Davis Medical Center
2315 Stockton Boulevard
Sacramento, CA 95817