Study of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)

NCT01009294 | Terminated Phase 2 Results DMC

• 2 other identifiers: PTC124-GD-008-DMD2009-013169-24
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 6

Brief Summary

Duchenne/Becker muscular dystrophy (DMD/BMD) 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 DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a trial that enrolled boys with nonsense mutation DMD/BMD who have lost independent mobility due to the disease. This study evaluated the safety and tolerability of ataluren (PTC124) and also evaluated efficacy outcomes in this participant population.

Conditions

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; Becker muscular dystrophy; Nonsense mutation; Premature stop codon; DMD; BMD; 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 Day 50

Secondary Outcomes (17)

• Time to Complete Upper Limb Function Tasks as Measured by the Jebsen Test

  Baseline and Week 6

• Upper Limb Function as Measured by the Brooke Upper Extremity Functional Rating Scale

  Baseline and Week 6

• Participant Activities of Daily Living as Assessed Using the Egen Klassifikation (EK) Scale

  Baseline and Week 6

• Shoulder, Elbow, and Wrist Passive and Active Range of Motion as Measured by Goniometry

  Baseline and Week 6

• Force Exerted During Elbow Flexion and Extension, Shoulder Abduction, Hand Grip, Key Grip, and Finger Pinch as Assessed by Upper Extremity Myometry

  Baseline and Week 6

Study Arms (1)

Ataluren

EXPERIMENTAL

Ataluren was provided as a vanilla-flavored powder to be mixed with water, apple juice, or milk. Study drug dosing was based on milligrams of drug per kilogram of body weight. The dose level for ataluren was 20 milligrams/kilograms (mg/kg) in the morning, 20 mg/kg at midday, and 40 mg/kg in the evening. Administration within 30 minutes after a meal was recommended. Study drug was taken for up to 50 days.

Drug: Ataluren; Drug: Chronic Corticosteroid Therapy

Interventions

Ataluren DRUG

Oral powder

Also known as: PTC124

Ataluren

Chronic Corticosteroid Therapy DRUG

Enrollment was stratified to ensure evaluation of approximately half of the participants were receiving chronic corticosteroid therapy and approximately half of participants were not receiving chronic corticosteroid therapy. Therefore, 3 out of 6 participants were receiving chronic corticosteriod therapy. For the participants receiving chronic corticosteriod therapy, a stable corticosteriod regimen was to be maintained during the study.

Ataluren

Eligibility Criteria

• Age: 7 Years+
• 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:

• Diagnosis of DMD or BMD
• Presence of a nonsense mutation in the dystrophin gene
• Unable to ambulate independently for ≥1 year due to DMD/BMD
• Presence of sufficient shoulder and elbow function to perform study-related functional procedures (for example, 9-hole peg test)
• Adequate hepatic, renal, and adrenal function
• Ability to provide evaluable pretreatment echocardiogram and lung function assessments
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age)

You may not qualify if:

• Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or use of systemic aminoglycoside antibiotic within 3 months prior to start of study treatment
• Use of any intermittent systemic corticosteroid therapy regimen (for example, 10 days on followed by 10 days off, weekend dosing, every-other-day dosing); note that participants must have either been receiving a daily dosing regimen of prednisone, prednisolone, or deflazacort at the time of enrollment into the study or must have not been receiving any systemic corticosteroids
• Any change in treatment for congestive heart failure within 3 months prior to start of study treatment
• Ongoing warfarin or phenytoin therapy
• Prior therapy with ataluren
• 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).
• Exposure to another investigational drug within 2 months prior to start of study treatment
• History of major surgical procedure within 1 month prior to start of study treatment or expectation of major surgical procedure (for example, scoliosis surgery) during the 48-week treatment period of the study
• Ongoing immunosuppressive therapy (other than corticosteroids)
• Ongoing participation in any other clinical trial
• Requirement for daytime ventilator assistance
• Uncontrolled clinical symptoms and signs of congestive heart failure
• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results

Sponsors & Collaborators

• PTC Therapeutics: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (6)

University of California-Davis

Davis, California, 95616, United States

Location

Children's Hospital of Boston

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Newcastle

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Location

Related Links

• Related Info

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

• Leone Atkinson, MD, PhD

  PTC Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2009
• First Posted: November 6, 2009
• Study Start: January 13, 2010
• Primary Completion: March 23, 2010
• Study Completion: March 23, 2010
• Last Updated: July 29, 2020
• Results First Posted: July 29, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); GB (1)