Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of two different weekly doses of RO7239361 in ambulatory boys with Duchenne Muscular Dystrophy (DMD).

Official Title
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A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: RO7239361
* Drug: Placebo for RO7239361


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with DMD by confirmed medical history and genetic testing Able to walk without assistance Minimum North Star Ambulatory Assessment score of 15 at screening Able to walk up 4 stairs in 8 seconds or less Weigh at least 15 kg (33 lbs) Taking corticosteroids for DMD Exclusion Criteria: 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 Concomitant or previous participation at any time in a gene therapy study Other protocol defined Inclusion/Exclusion Criteria could apply.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO7239361 Low Dose<br>Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up. | Drug: RO7239361<br>* Take RO7239361 subcutaneously on specified days over a 48 week blinded period<br>|
| Experimental: RO7239361 High Dose<br>Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up. | Drug: RO7239361<br>* Take RO7239361 subcutaneously on specified days over a 48 week blinded period<br>|
| Placebo Comparator: Placebo<br>Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up. | Drug: Placebo for RO7239361<br>* Take placebo subcutaneously on specified days over a 48 week blinded period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline for the North Star Ambulatory Assessment (NSAA) Total Score | The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. | Baseline | 
| Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 | The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Time for 4 Stair Climb | The time to complete the 4 stair climb was measured at baseline. | Baseline | 
| Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) | 4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). | Baseline, Week 48 | 
| Baseline for the Time to Stand From Supine | The time required for a participant to stand from supine position. A longer time reflects a worse outcome. | Baseline | 
| Change From Baseline at Week 48 in Stand From Supine Velocity | The time required for a participant to stand from supine position. A longer time reflects a worse outcome. A negative change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). | Baseline, Week 48 | 
| Baseline Time for 10 Meter Walk/Run | The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome. | Baseline | 
| Change From Baseline at Week 48 in 10 M Walk/Run Velocity | The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). | Baseline, Week 48 | 
| Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. | Baseline | 
| Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale | The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). | Baseline, Week 48 | 
| Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength | Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement. | Baseline, Week 48 | 
| Baseline for the 6 Minute Walk Distance (6MWD) | The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. | Baseline | 
| Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) | The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). | Baseline, Week 48 | 
| Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 | The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse at Week 48 as compared to baseline. | Baseline, Week 48 | 
| Change From Baseline at Week 48 in 95th Percentile Stride Velocity | Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement. | Baseline, Week 48 | 
| Number of Participants With Adverse Events (AEs) | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | During DB period (48 weeks) and Whole study (up to approximately 34 months) | 
| Number of Participants With AEs Leading to Discontinuation | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation. | During DB period (48 weeks) and Whole study (up to approximately 34 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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muscular dystrophy, Duchenne's Muscular Dystrophy, DMD