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

• ClinicalTrials.gov Identifier: NCT03039686
• Recruitment Status: Completed
• First Posted: February 1, 2017
• Results First Posted: December 21, 2020
• Last Update Posted: December 21, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 27, 2017
• First Posted Date: February 1, 2017
• Results First Submitted Date: October 21, 2020
• Results First Posted Date: December 21, 2020
• Last Update Posted Date: December 21, 2020
• Actual Study Start Date: July 6, 2017
• Actual Primary Completion Date: April 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 21, 2020)

• Baseline for the North Star Ambulatory Assessment (NSAA) Total Score [ Time Frame: Baseline ]
  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.
• Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48 [ Time Frame: Baseline, 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).

Original Primary Outcome Measures (submitted: January 31, 2017)

• Change from baseline in the 4 stair climb velocity in BMS-986089 treated participants. [ Time Frame: 48 Week ]
• Change from baseline in the 4 stair climb velocity in placebo treated participants. [ Time Frame: 48 Week ]

Current Secondary Outcome Measures (submitted: November 25, 2020)

• Baseline Time for 4 Stair Climb [ Time Frame: Baseline ]
  The time to complete the 4 stair climb was measured at baseline.
• Change From Baseline at Week 48 in 4 Stair Climb Velocity (4SCV) [ Time Frame: Baseline, Week 48 ]
  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 for the Time to Stand From Supine [ Time Frame: Baseline ]
  The time required for a participant to stand from supine position. A longer time reflects a worse outcome.
• Change From Baseline at Week 48 in Stand From Supine Velocity [ Time Frame: Baseline, Week 48 ]
  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 Time for 10 Meter Walk/Run [ Time Frame: Baseline ]
  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.
• Change From Baseline at Week 48 in 10 M Walk/Run Velocity [ Time Frame: Baseline, Week 48 ]
  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 for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale [ Time Frame: Baseline ]
  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.
• Change From Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale [ Time Frame: Baseline, Week 48 ]
  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).
• Change From Baseline at Week 48 in Proximal Lower Extremity Flexor Strength [ Time Frame: Baseline, Week 48 ]
  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 for the 6 Minute Walk Distance (6MWD) [ Time Frame: Baseline ]
  The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome.
• Change From Baseline at Week 48 in 6 Minute Walk Distance (6MWD) [ Time Frame: Baseline, Week 48 ]
  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).
• Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48 [ Time Frame: Baseline, 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.
• Change From Baseline at Week 48 in 95th Percentile Stride Velocity [ Time Frame: Baseline, Week 48 ]
  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.
• Number of Participants With Adverse Events (AEs) [ Time Frame: During DB period (48 weeks) and Whole study (up to approximately 34 months) ]
  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.
• Number of Participants With AEs Leading to Discontinuation [ Time Frame: During DB period (48 weeks) and Whole study (up to approximately 34 months) ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy
• Official Title: A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

• Drug: RO7239361
  Take RO7239361 subcutaneously on specified days over a 48 week blinded period
• Drug: Placebo for RO7239361
  Take placebo subcutaneously on specified days over a 48 week blinded period

Study Arms

• Experimental: RO7239361 Low Dose
  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.
  Intervention: Drug: RO7239361
• Experimental: RO7239361 High Dose
  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.
  Intervention: Drug: RO7239361
• Placebo Comparator: Placebo
  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.
  Intervention: Drug: Placebo for RO7239361

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 25, 2019): 166
• Original Estimated Enrollment (submitted: January 31, 2017): 159
• Actual Study Completion Date: April 28, 2020
• Actual Primary Completion Date: April 28, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 6 Years to 11 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Canada, France, Germany, Italy, Japan, Netherlands, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03039686
• Other Study ID Numbers: CN001-016; 2016-001654-18 ( EudraCT Number ); WN40227 ( Other Identifier: Hoffman-La Roche )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Bristol-Myers Squibb
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: November 2020