| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Duchenne Muscular Dystrophy |
|
| E.1.1.1 | Medical condition in easily understood language |
| Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10013801 |
| E.1.2 | Term | Duchenne muscular dystrophy |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| 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 |
| To compare the efficacy of RO7239361 to placebo in ambulatory boys with Duchenne muscular dystrophy |
|
| E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of RO7239361 to placebo using the following tests:
- 4 stair climb velocity (4SCV)
- Stand from supine velocity
- 10 M walk/run velocity
- PODCI transfers and basic mobility subscale
- Proximal lower extremity flexor (knee extension and knee flexion) strength, measured using manual myometry
- 6 Minute Walk Distance (6MWD)
- Clinical Global Impression of Change (CGI-C)
- Stride velocity recorded with ActiMyo
• To assess the safety and tolerability of RO7239361 in boys with DMD as reflected by new or worsening lab abnormalities (as defined by CTCAE criteria), serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Additional research collections and retention are optional for all subjects, except where prohibited by local laws or regulations.
This protocol will include both sample collection and residual sample storage for additional research (AR).
This serum collection for additional research is intended to expand the translational R&D capability at Roche, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. For example, this sample may have potential in exploration of diagnostic or prognostic biomarkers contingent on scientific developments in the field of myostatin biology, DMD pathophysiology or unanticipated results in the study.
This collection for additional research is intended to expand the translational R&D capability at Roche, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc.
|
|
| E.3 | Principal inclusion criteria |
Key Inclusion Criteria:
• Males, 6 >= to < 12 years of age at time of randomization.
• Diagnosis of DMD, confirmed by medical history (eg., onset of clinical signs or symptoms before 5 years of age together with an elevated serum creatine kinase level observed before or after initial diagnosis) and by genotyping.
• Participants >= 15 kg.
• Ambulatory without assistance.
• Participants must be receiving corticosteroids (CS, prednisone, prednisolone, or deflazacort) for at least 6 months prior to the start of study drug, with no significant change in dosage (> 0.2 mg/kg prednisone or > 0.24 mg/kg deflazacort) or dosing regimen for at least 12 weeks prior to the start of study drug, with the expectation that dosage and dosing regimen will not change significantly for the duration of the study.
• North Star Ambulatory Assessment (NSAA) score >=15 points at screening
• 4SC<= 8 seconds at screening.
• Subjects must agree to avoid major changes in their physical or respiratory therapy regimen during the double blind phase, to the extent possible.
• Subjects who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) plus 5 half-lives of the study treatment [RO7239361; 50 days] plus 90 days (duration of sperm turnover) for a total of 140 days (5 months) post-treatment completion.
For the rest of Inclusion Criteria, please refer to study protocol Section 6.1 (page 50). |
|
| E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
• Participants with cognitive impairment or behavioral issues that, in the judgement of the investigator, will compromise their ability to comply with study procedures.
• Participants on intermittent CS regimens with off periods of 20 days or longer (eg.: 10 days on, 20 days off).
• Any change (initiation, change in drug class, dose modification unrelated to change in body weight, interruption or re-initiation) in prophylaxis /treatment for congestive heart failure (CHF) within 12 weeks prior to start of study treatment.
• Any change (initiation, change in drug class, dose modification unrelated to change in body weight, interruption or re-initiation) in prophylaxis/treatment for bone density within 12 weeks prior to start of study treatment.
• Treatment with exon skipping therapies within 6 months prior to the start of study drug administration.
• Treatment with ataluren currently or within 12 weeks prior to the start of study drug administration.
• Treatment with any other investigational drug (excluding deflazacort in CS dose-finding trials) currently or within 12 weeks prior to the start of study drug administration.
• Concurrent or previous participation at any time in a gene therapy study.
• Participants with a FVC of < 50% of predicted value (in participants able to produce a valid FVC, as judged by the clinical evaluator or respiratory therapist).
• Cutaneous AEs sustained during participation in a prior clinical trial that resolved less than 12 weeks prior to the start of study drug administration.
• Current or prior treatment within 12 weeks prior to the start of study drug administration with androgens or human growth hormone.
• Prior treatment with RO7239361 or any other anti-myostatin agent.
• History of lower limb fracture within 12 weeks prior to the start of study drug administration.
• History of upper limb fracture within 8 weeks prior to the start of study drug administration.
• Any injury that may impact functional testing. Previous injuries must be fully healed prior to consenting.
• Expectation of major surgical procedure, such as scoliosis surgery, during the double blind phase of this study.
• Requirement of daytime ventilator assistance.
• Initiation of nighttime ventilation less than 4 weeks prior to the start of study drug administration.
• Expectation that daytime or nighttime ventilation may be initiated during the double blind phase of this study.
• Clinical signs or symptoms of uncontrolled congestive heart failure (CHF) (American College of Cardiology/American Heart Associated Stage C or Stage D).
• For participants participating in cMRI substudy: implanted ferromagnetic metal (implanted metal that is not ferromagnetic, such as surgical steel or titanium implants may be allowed if the implants will not compromise the quality of the cMRI).
• History of hypersensitivity to components of the study drug (histidine, trehalose, diethylenetriaminepentaacetic acid, polysorbate 80).
• Unwilling or unable to administer study drug at home.
For the rest of Exclusion Criteria, please refer to study protocol Section 6.2 (page 51). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The change from baseline in the North Star Ambulatory Assessment (NSAA) total score at Week 48 in RO723936-treated participants compared to placebo-treated participants. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, week 12, week 24, week 36 and week 48 during double blind phase.
Week 1, week 12, week 24, week 36 and week 48 during open label phase.
|
|
| E.5.2 | Secondary end point(s) |
• Change from baseline at Week 48 in RO7239361-treated participants compared to placebo-treated participants in the following:
- 4 stair climb velocity (4SCV)
- Stand from supine velocity
- 10 M walk/run velocity
- PODCI transfers and basic mobility subscale
- Proximal lower extremity flexor (knee extension and knee flexion) strength, measured using manual myometry
- 6-Minute Walk Distance (6MWD)
- Clinical Global Impression of Change (CGI-C)
- 95th percentile stride velocity, as recorded with ActiMyo in a subset of the overall study population
• Tabulations of the numbers of unique participants with new or worsening laboratory abnormalities, SAEs and AEs leading to discontinuation, in RO7239361 arms compared to the placebo arm. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, week 12, week 24, week 36 and week 48 during double blind phase.
Week 1, week 12, week 24, week 36 and week 48 during open label phase. |
|
| 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 | Yes |
| 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| 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.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 | No |
| 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 |
| Argentina |
| Australia |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Japan |
| Netherlands |
| Spain |
| Sweden |
| United Kingdom |
| United States |
|
| 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 defined as the last visit or scheduled procedure shown in the Schedule of Activities for the last participant. Study completion is defined as the final date on which data for the primary endpoint was or is expected to be collected, if this is not the same. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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