Study of ataluren in patients with nonsense mutation Duchenne and Becker muscular dystrophy

Phase 1

Conditions: onsense mutation dystrophinopathy
MedDRA version: 18.0 Level: PT Classification code 10059117 Term: Becker's muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 18.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2012-004527-20-FR

Lead Sponsor: PTC Therapeutics, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 220

Inclusion Criteria

1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial
2. Male sex
3. Age =7 and =16 years.
4. 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 CK, and ongoing difficulty with ambulation.
5. Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by College of American Pathologists (CAP), Clinical Laboratory Improvement Act/Amendment (CLIA), or an equivalent organization.
6. Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
7. 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.
8. Valid Screening 6MWD =150 meters. Valid Screening 6MWD must be =80% of predicted for age and height [Geiger 2007].
9.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.
10. Baseline 6MWD (mean valid Day 1 and Day 2 values) must be no more than a 20% reduction from the valid Screening 6MWD.
11. Confirmed screening laboratory values within the central laboratory ranges specified in in the protocol.
12. In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 6-week follow-up period.
13. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Are the trial subjects under 18? yes
Number of subjects for this age range: 220
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
2. Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment.
3. 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.
4. 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.
5. Ongoing use of coumarin-based anticoagulants (eg. warfarin), phenytoin, tolbutamide, or paclitaxel.
6. Prior therapy with ataluren.
7. Known hypersensitivity to any of the ingredients or excipients of the study drug [eg. refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium stearate]
8. Exposure to another investigational drug within 3 months prior to start of study treatment.
9. History of major surgical procedure within 6 weeks prior to start of study treatment
10. Ongoing immunosuppressive therapy (other than corticosteroids)
11. Ongoing participation in any clinical trial (except for studies specifically approved by PTC Therapeutics)
12. Expectation of major surgical procedure (eg, scoliosis surgery) during the 12-month treatment period of the study.
13. Requirement for daytime ventilator assistance.
14. Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D) [Hunt 2001]
15. 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Change in 6MWD;Main Objective: To determine the ability of ataluren to slow disease progression as assessed by ambulatory decline (decrease in 6MWD) in patients with nonsense mutation dystrophinopathy.;Timepoint(s) of evaluation of this end point: Screening visit and every 8 weeks;<br> Secondary Objective: To determine the effect of ataluren on:<br> - Ambulation<br> - Proximal muscle function<br> - Physical function<br> - Patient and/or parent reported activities of daily living and disease symptoms<br> - Parent-reported HRQL<br> - Safety parameters<br> - Compliance<br> - Exposure of ataluren in plasma<br>

Secondary Outcome Measures

Name	Time	Method

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