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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00592553




Registration number
NCT00592553
Ethics application status
Date submitted
1/01/2008
Date registered
14/01/2008

Titles & IDs
Public title
Phase 2B Study of PTC124 (Ataluren) in Duchenne/Becker Muscular Dystrophy (DMD/BMD)
Scientific title
A Phase 2B Efficacy and Safety Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne and Becker Muscular Dystrophy
Secondary ID [1] 0 0
2007-005478-29
Secondary ID [2] 0 0
PTC124-GD-007-DMD
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Duchenne Muscular Dystrophy 0 0
Becker Muscular Dystrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ataluren
Treatment: Drugs - Placebo

Experimental: High-Dose Ataluren - Participants will receive ataluren suspension orally 3 times a day (TID), 20 milligrams/kilogram (mg/kg) at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.

Experimental: Low-Dose Ataluren - Participants will receive ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.

Placebo comparator: Placebo - Participants will receive placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.


Treatment: Drugs: Ataluren
Ataluren will be administered as per the dose and schedule specified in the respective arms.

Treatment: Drugs: Placebo
Placebo matching to ataluren will be administered as the schedule specified in the respective arm.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in 6MWD at Week 48
Timepoint [1] 0 0
Baseline, Week 48
Secondary outcome [1] 0 0
Change From Baseline in Time to Stand From Supine Position at Week 48
Timepoint [1] 0 0
Baseline, Week 48
Secondary outcome [2] 0 0
Change From Baseline in Time to Walk/Run 10 Meters at Week 48
Timepoint [2] 0 0
Baseline, Week 48
Secondary outcome [3] 0 0
Change From Baseline in Time to Climb 4 Stairs at Week 48
Timepoint [3] 0 0
Baseline, Week 48
Secondary outcome [4] 0 0
Change From Baseline in Time to Descend 4 Stairs at Week 48
Timepoint [4] 0 0
Baseline, Week 48
Secondary outcome [5] 0 0
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry
Timepoint [5] 0 0
Baseline, Week 48
Secondary outcome [6] 0 0
Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM)
Timepoint [6] 0 0
Baseline, Week 48
Secondary outcome [7] 0 0
Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM
Timepoint [7] 0 0
Baseline, Week 48
Secondary outcome [8] 0 0
Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM
Timepoint [8] 0 0
Baseline, Week 48
Secondary outcome [9] 0 0
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM
Timepoint [9] 0 0
Baseline, Week 48
Secondary outcome [10] 0 0
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [=] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48
Timepoint [10] 0 0
Baseline, Week 48
Secondary outcome [11] 0 0
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48
Timepoint [11] 0 0
Baseline, Week 48
Secondary outcome [12] 0 0
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48
Timepoint [12] 0 0
Baseline, Week 48
Secondary outcome [13] 0 0
Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48
Timepoint [13] 0 0
Baseline, Week 48
Secondary outcome [14] 0 0
Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48
Timepoint [14] 0 0
Baseline, Week 48
Secondary outcome [15] 0 0
Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score
Timepoint [15] 0 0
Week 48
Secondary outcome [16] 0 0
Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48
Timepoint [16] 0 0
Baseline, Week 48
Secondary outcome [17] 0 0
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48
Timepoint [17] 0 0
Baseline, Week 48
Secondary outcome [18] 0 0
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400
Timepoint [18] 0 0
Baseline, Week 48
Secondary outcome [19] 0 0
Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48
Timepoint [19] 0 0
Baseline, Week 48
Secondary outcome [20] 0 0
Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence
Timepoint [20] 0 0
Pre-Treatment (1 week prior to baseline), post-treatment (Week 36)

Eligibility
Key inclusion criteria
* Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age).
* Male sex.
* Age =5 years.
* Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs (that is, proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9 years of age, an elevated serum CK level, and ongoing difficulty with ambulation.
* Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA), or an equivalent organization.
* Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
* Ability to walk =75 meters unassisted during the screening 6-minute walk test. Note: Other personal assistance or use of assistive devices for ambulation (for example, short leg braces, long leg braces or walkers) were not permitted.
* Confirmed screening laboratory values within the central laboratory ranges (hepatic, adrenal, renal, and serum electrolytes parameters).
* In participants who were sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 6-week follow-up periods.
* 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 (in particular, the ability to satisfactorily perform the 6MWT) should have been considered.
Minimum age
5 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
* Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or change in systemic corticosteroid therapy (for example, initiation, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, or reinitiation) within 3 months prior to start of study treatment.
* Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure within 3 months prior to start of study treatment.
* Treatment with warfarin within 1 month prior to start of study treatment.
* Prior therapy with ataluren.
* Known hypersensitivity to any of the ingredients or excipients of the study drug (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 30 days prior to start of study treatment.
* Ongoing immunosuppressive therapy (other than corticosteroids).
* Ongoing participation in any other therapeutic clinical trial.
* Expectation of major surgical procedure (for example, scoliosis surgery) during the 12-month treatment period of the study.
* Requirement for daytime ventilator assistance.
* Clinical symptoms and signs of congestive heart failure (American College of Cardiology/American Heart Association Stage C or Stage D) or evidence on echocardiogram of clinically significant myopathy.
* Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [2] 0 0
Institute For Neuromuscular Research, The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
France
State/province [20] 0 0
Marseille
Country [21] 0 0
France
State/province [21] 0 0
Nantes
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
Germany
State/province [23] 0 0
Essen
Country [24] 0 0
Germany
State/province [24] 0 0
Freiburg
Country [25] 0 0
Israel
State/province [25] 0 0
Jerusalem
Country [26] 0 0
Italy
State/province [26] 0 0
Milan
Country [27] 0 0
Italy
State/province [27] 0 0
Rome
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Valencia
Country [30] 0 0
Sweden
State/province [30] 0 0
Göteborg
Country [31] 0 0
Sweden
State/province [31] 0 0
Stockholm
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Newcastle
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Oswestry

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
PTC Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Leone Atkinson, MD, PhD
Address 0 0
PTC Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.