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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01009294
• Date of registration: 05/11/2009
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics
• Public title: Study of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)
• Scientific title: A Phase 2a Study of Ataluren (PTC124) in Nonambulatory Patients With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy
• Date of first enrolment: January 13, 2010
• Target sample size: 6
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01009294
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Leone Atkinson, MD, PhD
• Affiliation: PTC Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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)

Exclusion Criteria:

- 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



Age minimum: 7 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Becker Muscular Dystrophy

Intervention(s)

Drug: Chronic Corticosteroid Therapy

Drug: Ataluren

Primary Outcome(s)

Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Time Frame: Baseline up to Day 50]

Secondary Outcome(s)

Forced Vital Capacity (FVC) as Measured by Spirometry [Time Frame: Baseline and Week 6]

HRQL as Measured by the INQoL [Time Frame: Week 24 and Week 48]

Time to Complete Hand Fine Motor Coordination and Dexterity Tasks as Measured by 9-Hole Peg Test (9HPT) [Time Frame: Baseline and Week 6]

Participant Activities of Daily Living as Assessed Using the Egen Klassifikation (EK) Scale [Time Frame: Baseline and Week 6]

Upper Limb Function as Measured by the Brooke Upper Extremity Functional Rating Scale [Time Frame: 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 [Time Frame: Baseline and Week 6]

Systolic and Diastolic Function as Measured by Echocardiography With Tissue Doppler [Time Frame: Week 24 and Week 48]

Shoulder, Elbow, and Wrist Passive and Active Range of Motion as Measured by Goniometry [Time Frame: Baseline and Week 6]

Study Drug Compliance [Time Frame: Baseline to Day 50]

Gastrocnemius Muscle Dystrophin Expression as Determined by Immunofluoresence or by Western Blotting Techniques [Time Frame: Week 36]

Heart Rate as Assessed by Radial Pulse [Time Frame: Baseline and Week 6]

HRQL as Measured by the PedsQL Inventory Generic Core Scale [Time Frame: Week 6]

HRQL as Measured by the PedsQL Multidimensional Fatigue Scale [Time Frame: Week 6]

Muscle Fragility as Determined by Serum Creatine Kinase (CK) Levels [Time Frame: Baseline and Week 6]

Pharmacokinetics: Ataluren Plasma Exposure [Time Frame: 0, 2, 3, 6, 8, 9, 12, 14, 15, and 24 hours after the morning dose]

Verbal Memory and Attention as Assessed by the Digit Span Task [Time Frame: Baseline and Week 6]

Time to Complete Upper Limb Function Tasks as Measured by the Jebsen Test [Time Frame: Baseline and Week 6]

Secondary ID(s)

PTC124-GD-008-DMD

2009-013169-24

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genzyme, a Sanofi Company

Results

• Results available: Yes
• Date Posted: 29/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01009294