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

NCT01557400 | Completed Phase 3 Results

• 1 other identifier: PTC124-GD-019-DMD
• Study Type: interventional
• Target: 94
• Locations: 10 countries
• Sites: 21

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).

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline up to Week 246

Secondary Outcomes (6)

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

  Baseline, Weeks 48, 96, 144, 192, and 240

• Change From Baseline in Physical Function as Measured by the NSAA

  Baseline, Weeks 48, 96, 144, 192, and 240

• Change From Baseline in Time to Stand From Supine Position

  Baseline, Weeks 48, 96, 144, 192, and 240

• Change From Baseline in Time to Walk/Run 10 Meters

  Baseline, Weeks 48, 96, 144, 192, and 240

• Change From Baseline in Pulmonary Function as Measured by Spirometry

  Baseline, Weeks 48, 96, 144, 192, and 240

Study Arms (1)

Ataluren

EXPERIMENTAL

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.

Drug: Ataluren

Interventions

Ataluren DRUG

Oral powder for suspension

Also known as: PTC124®

Ataluren

Eligibility Criteria

• Gender Eligibility Details: Male participants only are being studied.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• Male sex.
• 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.
• 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.

You may not qualify if:

• Exposure to another investigational drug within 1 month prior to start of study treatment.
• Eligibility for another ataluren clinical trial that is actively enrolling study participants.
• 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).
• Ongoing use of the following medications:
• Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or paclitaxel.
• Systemic aminoglycoside therapy
• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (21)

Royal Children's Hospital

Parkville, Melbourne, Australia

Location

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

Westmead, Australia

Location

University Hospital KU Leuven

Leuven, Belgium

Location

Alberta Children's Hospital

Calgary, Alberta, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, Canada

Location

Hôpital d'Enfants CHU Timone

Marseille, France

Location

Laboratoire d'Exploration Fonctionnelles

Nantes, France

Location

Groupe Hospitalier La Pitie-Salpetriere

Paris, France

Location

University of Essen - Clinic for Children

Essen, Germany

Location

University Hospital

Freiburg im Breisgau, Germany

Location

Hadassah Medical Center, Hebrew University Hospital

Jerusalem, Israel

Location

Ospedale Maggiore Policlinico in Milan

Milan, Italy

Location

Ospedale Pediatrico Bambino Gesu

Rome, Italy

Location

U.O. Complessa di Neuropsichiatria Infantile

Rome, Italy

Location

Hospital Sant Joan de déu

Barcelona, Spain

Location

Hospital Universitari La Fe

Valencia, Spain

Location

Queen Silvia Children's Hospital

Gothenburg, Sweden

Location

Astrid Lindgren Pediatric Hospital

Stockholm, Sweden

Location

Great Ormond Street Hospital

London, United Kingdom

Location

University of Newcastle Institute of Human Genetics

Newcastle upon Tyne, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 17450125 BACKGROUND

• 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.

  PMID: 17389552 BACKGROUND

• 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.

  PMID: 34791888 DERIVED

Related Links

• 16-2-9 CINRG Listing

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

ataluren

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Edward O'Mara, MD

  PTC Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: March 19, 2012
• Study Start: May 20, 2012
• Primary Completion: January 19, 2018
• Study Completion: January 19, 2018
• Last Updated: November 25, 2020
• Results First Posted: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); DE (2); GB (2); AU (2); SE (2); FR (3); BE (1); IL (1); IT (3); ES (2)