Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada

PTC Therapeutics94 enrolled

Overview

Duchenne/Becker muscular dystrophy (DBMD) 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 DBMD in approximately 10-15% of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study comprises a Phase 3, open-label study of ataluren in participants with nmDBMD who previously received ataluren at an Investigator site in a prior PTC-sponsored clinical study. A separate open-label study (PTC124-GD-016-DMD; NCT01247207) is being conducted for nmDBMD participants who previously received ataluren at an Investigator site in the United States (US).

All participating sites must have had at least 1 participant that received ataluren treatment in prior PTC-sponsored clinical studies in DBMD (Phase 2b double-blind, placebo-controlled study \[PTC124-GD-007-DMD; NCT00592553\] and the subsequent open-label extension study \[Study PTC124-GD-007e-DMD; NCT00847379\]). It is planned that up to \~96 participants will be enrolled. It is also planned that participants will receive ataluren 3 times per day (TID) at respective morning, midday, and evening doses of 10 milligrams/kilograms (mg/kg), 10 mg/kg, and 20 mg/kg for approximately 336 weeks. Study assessments will be performed at clinic visits during screening, on the first day of ataluren dosing, and then every 48 weeks during the ataluren treatment period, except for weight, which will be measured every 24 weeks at a primary care physician (PCP).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: MALE

Medical Language ↔ Plain English

Inclusion Criteria: 1. Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethics Committee (IRB/IEC) regarding whether 1 or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed. 2. History of exposure to ataluren in a prior PTC study in nmDBMD. Note: Participants are considered eligible only if they received ataluren during their participation in 1 or more prior PTC-sponsored studies of ataluren in nmDBMD. Note: Participants who have participated in a prior or ongoing PTC study with ataluren in nmDBMD at a trial site in the US or Canada, but reside outside of the US and Canada, may be eligible for this study (with the approval of the PTC Therapeutics Medical Monitor). 3. Male sex. 4. In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 6-week follow-up period. 5. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered. Exclusion Criteria: 1. Exposure to another investigational drug within 1 month prior to start of study treatment. 2. Eligibility for another ataluren clinical trial that is actively enrolling study participants. 3. 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). 4. Ongoing use of the following medications: 1. Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or paclitaxel. 2. Systemic aminoglycoside therapy 5. Ongoing uncontrolled medical/surgical condition, electrocardiogram (ECG) findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant or make it unlikely that follow-up would be completed.

Locations (21)

Royal Children's Hospital

Parkville, Melbourne, Australia

Institute For Neuromuscular Research, The Children's Hospital at Westmead

Westmead, Australia

University Hospital KU Leuven

Leuven, Belgium

Alberta Children's Hospital

Calgary, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Children's Hospital of Western Ontario

London, Ontario, Canada

Hôpital d'Enfants CHU Timone

Marseille, France

Laboratoire d'Exploration Fonctionnelles

Nantes, France

Groupe Hospitalier La Pitie-Salpetriere

Paris, France

University of Essen - Clinic for Children

Essen, Germany

...and 11 more locations

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

A TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of the study drug or study treatment, whether or not considered related to the treatment by the Investigator. A serious adverse event (SAE) was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), or persistent or significant disability/incapacity not related to nmDBMD. AEs included both SAEs and non-serious AEs. AEs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) and coded using the Medical Dictionary for Regulatory Activities (MedDRA). A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Time frame: Baseline up to Week 246

Secondary Outcomes

Change From Baseline in 6MWD as Measured by the 6MWT

The 6MWD was assessed in participants who were ambulatory using standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test.