Study of ataluren in patients with nonsense mutation Duchenne and Becker muscular dystrophy

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2012-004527-20-GB
• Date of registration: 24/06/2013
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics, Inc
• Public title: Study of ataluren in patients with nonsense mutation Duchenne and Becker muscular dystrophy
• Scientific title: A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients with Nonsense Mutation Dystrophinopathy - N/A
• Date of first enrolment: 08/08/2013
• Target sample size: 220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004527-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, Chile, Czech Republic, France, Germany, Israel, Italy, Korea, Republic of, Poland, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial
2. Male sex
3. Age =7 and =16 years.
4. Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (eg, proximal muscle weakness, waddling gait, and Gowers’ maneuver) by 6 years of age, an elevated serum CK, and ongoing difficulty with ambulation.
5. Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by College of American Pathologists (CAP), Clinical Laboratory Improvement Act/Amendment (CLIA), or an equivalent organization.
6. Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
7. Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
8. Valid Screening 6MWD =150 meters. Valid Screening 6MWD must be =80% of predicted for age and height [Geiger 2007].
9.Results of the 2 Baseline 6MWD results must be determined as valid and results of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.
10. Baseline 6MWD (mean valid Day 1 and Day 2 values) must be no more than a 20% change from the valid Screening 6MWD.
11. Confirmed screening laboratory values within the central laboratory ranges specified in in the protocol.
12. In subjects who are 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 period.
13. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Are the trial subjects under 18? yes
Number of subjects for this age range: 220
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
2. Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment.
3. Change in systemic corticosteroid therapy (eg, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, or reinitiation) within 3 months prior to start of study treatment.
4. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart
failure (CHF) within 3 months prior to start of study treatment.
5. Ongoing use of coumarin-based anticoagulants (eg. warfarin), phenytoin, tolbutamide, or paclitaxel.
6. Prior therapy with ataluren.
7. Known hypersensitivity to any of the ingredients or excipients of the study drug [eg. refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium stearate]
8. Exposure to another investigational drug within 3 months prior to start of study treatment.
9. History of major surgical procedure within 6 weeks prior to start of study treatment
10. Ongoing immunosuppressive therapy (other than corticosteroids)
11. Ongoing participation in any clinical trial (except for studies specifically approved by PTC Therapeutics)
12. Expectation of major surgical procedure (eg, scoliosis surgery) during the 12-month treatment period of the study.
13. Requirement for daytime ventilator assistance.
14. Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D) [Hunt 2001]
15. Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings (eg. lower limb injury that may affect 6MWT performance), ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Nonsense mutation dystrophinopathy
MedDRA version: 17.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 17.0 Level: PT Classification code 10059117 Term: Becker's muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Product Name: ataluren
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ataluren
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To determine the effect of ataluren on:
- Ambulation
- Proximal muscle function
- Physical function
- Patient and/or parent reported activities of daily living and disease symptoms
- Parent-reported HRQL
- Safety parameters
- Compliance
- Exposure of ataluren in plasma

Primary end point(s): Change in 6MWD

Timepoint(s) of evaluation of this end point: Screening visit and every 8 weeks

Main Objective: To determine the ability of ataluren to slow disease progression as assessed by ambulatory decline (decrease in 6MWD) in patients with nonsense mutation dystrophinopathy.

Secondary Outcome(s)

Secondary end point(s): 1. Time to 10% persistent worsening in 6MWD
2. Proportion of patients with =10% worsening in 6MWD at Week 48
3. Change in %-predicted 6MWD
4. Change in timed function tests (time to walk/run 10 meters and time to climb/descend 4 stairs)
5. Change in physical function as measured by the NSAA
6. Change in patient and/or parent/caregiver reports of activities of daily living as measured by a standardized survey administered by site personnel
7. Change in PODCI Transfers/Basic Mobility and Sports/Physical Functioning scores
8. Safety profile characterized by type, frequency, severity, timing, and relationship to study drug of any adverse events, or of abnormalities of laboratory tests, vital signs, physical examinations, or ECGs
9. Study drug compliance as assessed by quantification of unused study drug
10. Plasma concentration as assessed by a validated bioanalytical method

Timepoint(s) of evaluation of this end point: 1, 3, 4, 5, 6, 7: Screening visit and every 8 weeks
2. Week 48
8. Adverse events: every 8 weeks until end of treatment, then 6 weeks post-treatment
Laboratory tests and vital signs: Screening, every 8 weeks until end of treatment, then 6 weeks post-treatment
Physical examinations: Screening, week 1, week 24, week 48 and 6 weeks post-treatment
ECGs: Screening, week 48 and 6 weeks post-treatment
9, 10: Every 8 weeks from week 8

Secondary ID(s)

NCT01826487

2012-004527-20-BE

68,431

PTC124-GD-020-DMD

Source(s) of Monetary Support

PTC Therapeutics, Inc.

Ethics review

Status: Approved
Approval date:
Contact: