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 determine the safety and tolerability of RO7239361 in boys with Duchenne Muscular Dystrophy. | |
E.2.2 | Secondary objectives of the trial | To evaluate the following in boys with DMD: - Pharmacokinetics of multiple subcutaneous doses (SC) of RO7239361 - The immunogenicity of multiple SC doses of RO7239361 - The effects of RO7239361 on free myostatin and myostatin-drug complex levels - Magnetic resonance imaging (MRI) measures of right thigh maximal cross-sectional area (CSAmax), and contractile versus non-contractile content | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | - Males, >= 5 to < 11 years of age at time of randomization - Diagnosed with DMD - Able to walk without assistance - Able to walk up 4 stairs in 8 seconds or less - Weigh at least 15 kg - Taking corticosteroids for DMD | |
E.4 | Principal exclusion criteria | - Ejection fraction < 55% on echocardiogram, based on central read - Any behavior or mental issue that will affect the ability to complete the required study procedures - Previously or currently taking medications like androgens or human growth hormone - Use of a ventilator during the day - Unable to have blood samples collected or receive an injection under the skin - Treatment with exon skipping therapies 6 months prior to study start - Treatment with ataluren or any investigational drug currently or within 5 half-lives prior to study start | |
E.5 End points |
E.5.1 | Primary end point(s) | - Safety Summary for the 24 Week Double-Blind Phase - Safety Summary up to the End of the Open Label Phase at Week 72 | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | Up to Week 24 and up to Week 72 | |
E.5.2 | Secondary end point(s) | - Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses - Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose - Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses - Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose - Area Under the Concentration-Time Curve from Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses - Area Under the Concentration-Time Curve from Time Zero to Time of Next Dosing (AUCtau) of RO7239361 at Steady State for 50 mg QW Dose - Trough Serum Concentrations (Ctrough) of RO7239361 - Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase - Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to the End of the Open Label Phase - Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study - Serum Concentration of Free Myostatin - Percent Inhibition of Free Myostatin - Serum Concentration of Drug-Myostatin Complex - Fold Change from Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh - Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | Time frames for PK: Day 1: predose, 3, 6, 72 and 96 hours (h) postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose Time frames for ADA: DB: Day 8 up to Week 24, OL phase: Day 8 up to Week 72, Whole Study: Day 8 up to 228 weeks Other endpoints: Baseline up to Week 24 and up to end of study (up to Week 228) | |
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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | Yes |
E.7.1.3 | Other | No |
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 | 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 | 5 |
E.8.3 | Will this trial be conducted at a single site globally? | No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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 | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 13 |