| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Duchenne Muscular Dystrophy, Becker Muscular Dystrophy |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10013801 |
| E.1.2 | Term | Duchenne muscular dystrophy |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059117 |
| E.1.2 | Term | Becker's muscular dystrophy |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Evaluation of the ability of PTC124 to improve ambulation as assessed by change in 6-minute walking distance. |
|
| E.2.2 | Secondary objectives of the trial |
Comprehensive evaluation of the effects of PTC124 on major clinical manifestations of Duchenne and Becker Muscular Dystrophy and on the pathophysiology of the disease.
Safety and Exposure:
Safety parameters - Safety profile characterised by type, frequency, severity, timing, and relationship to study drug of any adverse event or laboratory abnormalities.
Compliance - Study drug compliance as assessed by a subject daily diary and quantification of used and unused study drug
PTC124 plasma exposure - Pre-dose and 2-hour post-dose PTC124 plasma concentrations after morning drug administation as assessed by a validated bioanalytical method |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. 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 Ethic Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the subject should be followed.
2. Male sex.
3. Age ≥5 years.
4. Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs (ie, proximal muscle weakness, waddling gait, and Gowers’ maneuver) by 9 years of age, an elevated serum CK, and ongoing diffculty with amublation. Note: Electromyography or prior muscle biopsy are not required for entry into this study. Specifically distinguishing DMD from BMD is not required. Medical documentation of phenotypic evidence of DMD/BMD needs to be provided upon request by the PTC Therapeutics medical monitor.
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. Note: A subject who has documentation of a nonsense mutation need not wait for confirmatory results to start study drug as long as the confirmatory genotyping blood sample has been drawn.
7. Ability to walk ≥75 meters unassisted during the Screening 6MWT. Note: Other personal assistance or use of assistive devices for ambulation (eg, short leg braces, long leg braces or walkers) is not permitted.
8. Confirmed screening laboratory values within the central laboratory ranges specified in the protocol. Note: Confirmation should be performed for out-of-range values to determine if the abnormality is real or artifactual. Values used to establish eligibility should be the last measurements obtained within the 6-week screening period.
9. 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 periods.
10. 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 be considered.
|
|
| E.4 | Principal 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 or change in systemic corticosteroid therapy (eg, 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. Note: Increases in corticosteroid dose (increase of less than/equal to 5 mg of prednisone or less than/equal to 6 mg of deflazacort) to adjust for increases in body weight will not exclude a subject from participation.
3. 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.
4. Treatment with warfarin within 1 month prior to start of study treatment.
5. Prior therapy with PTC124.
6. 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).
7. Exposure to another investigational drug within 2 months prior to start of study treatment.
8. History of major surgical procedure within 30 days prior to start of study treatment.
9. Ongoing immunosuppressive therapy (other than corticosteroids).
10. Ongoing participation in any other therapeutic clinical trial.
11. Expectation of major surgical procedure (eg, scoliosis surgery) during the 12 month treatment period of the study.
12. Requirement for daytime ventilator assistance.
13. Clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D) or evidence on echocardiogram of clinically significant myopathy. Note: An echocardiogram must have been performed within 2 years prior to study start for subjects <10 years and within 1 year for subjects 10 years or older.
14. Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, 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.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in 6-minute walking distance from baseline to Week-48 in the analysis population. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of trial is the last patient's visit. For each patient, blinded treatment ends at Week-48 , which is followed by a post-treatment visit at Week-54 . |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
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