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

NCT ID: NCT01557400

Last Updated: 2020-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-20
• Study Completion Date: 2018-01-19

Brief Summary

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).

Detailed Description

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).

Conditions

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Dystrophinopathy

Keywords

Duchenne muscular dystrophy; Becker muscular dystrophy; Nonsense mutation; Premature stop codon; DMD; BMD; nmDBMD; DBMD; Ataluren; PTC124

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ataluren

Ataluren will be provided as a vanilla-flavored powder to be mixed with water, milk, fruit juice (except apple juice) fruit punch, or in semi-solid food (for example, yogurt, pudding, or applesauce). The dose level for ataluren will be 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening. Administration within 30 minutes after a meal will be recommended. Study drug dosing will be based on milligrams of drug per kilogram of body weight. Because of potential changes in participant body weight over time, weight-based dose adjustment can occur every 24 weeks as required. Study drug will be taken for up to 240 weeks.

Group Type: EXPERIMENTAL

Ataluren

Intervention Type: DRUG

Oral powder for suspension

Interventions

Ataluren

Oral powder for suspension

Intervention Type: DRUG

Other Intervention Names

PTC124®

Eligibility Criteria

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.

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

PTC Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward O'Mara, MD

Role: STUDY_DIRECTOR

PTC Therapeutics

Locations

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

University Hospital

Freiburg im Breisgau, , Germany

Hadassah Medical Center, Hebrew University Hospital

Jerusalem, , Israel

Ospedale Maggiore Policlinico in Milan

Milan, , Italy

Ospedale Pediatrico Bambino Gesu

Rome, , Italy

U.O. Complessa di Neuropsichiatria Infantile

Rome, , Italy

Hospital Sant Joan de déu

Barcelona, , Spain

Hospital Universitari La Fe

Valencia, , Spain

Queen Silvia Children's Hospital

Gothenburg, , Sweden

Astrid Lindgren Pediatric Hospital

Stockholm, , Sweden

Great Ormond Street Hospital

London, , United Kingdom

University of Newcastle Institute of Human Genetics

Newcastle upon Tyne, , United Kingdom

Countries

Australia; Belgium; Canada; France; Germany; Israel; Italy; Spain; Sweden; United Kingdom

References

Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. doi: 10.1038/nature05756. Epub 2007 Apr 22.

Reference Type: BACKGROUND

PMID: 17450125 (View on PubMed)

Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44. doi: 10.1177/0091270006297140.

Reference Type: BACKGROUND

PMID: 17389552 (View on PubMed)

McDonald CM, Muntoni F, Penematsa V, Jiang J, Kristensen A, Bibbiani F, Goodwin E, Gordish-Dressman H, Morgenroth L, Werner C, Li J, Able R, Trifillis P, Tulinius M; Study 019 investigators. Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients. J Comp Eff Res. 2022 Feb;11(3):139-155. doi: 10.2217/cer-2021-0196. Epub 2021 Nov 18.

Reference Type: DERIVED

PMID: 34791888 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217411&parentIdentifier=PTC124-GD-019-DMD&attachmentIdentifier=0c3d8df5-876e-4f54-9b71-fcb919b589e6&fileName=PTC124-019-CSR-002514_1.0_PTC124-GD-019-DMD_Final_CSR_16-2-9_CINRG_Listing.pdf&versionIdentifier=

16-2-9 CINRG Listing

Other Identifiers

PTC124-GD-019-DMD

Identifier Type: -

Identifier Source: org_study_id