Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
Primary Purpose
Muscular Dystrophy (DMD)
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO7239361
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Muscular Dystrophy (DMD)
Eligibility Criteria
Inclusion Criteria:
- 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
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
Sites / Locations
- David Geffen School of Medicine at UCLA
- Stanford University
- University of Florida
- Nemours Children's Hospital
- Children's Healthcare of Atlanta
- Rush University Medical Center
- University of Kansas Medical Center
- Kennedy Krieger Institute
- Saint Louis Children's Hospital
- Cincinnati Children's Hospital Medical Center
- Alberta Children's Hospital
- Children'S Hospital of Eastern Ontario
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
RO7239361
Placebo
Arm Description
RO7239361 subcutaneous injections on specified days
Placebo subcutaneous injections on specified days
Outcomes
Primary Outcome Measures
Safety Summary for the 24 Week Double-Blind Phase
Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 24.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Safety Summary up to Week 72
Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 72.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Secondary Outcome Measures
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses.
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration.
Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361. No participants received the Panel 2 20mg dose.
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose.
PK parameter estimates at steady state following approximately 12 weeks QW administration.
Panel 3 = 50 mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
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.
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration.
Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW.
Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 6. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose.
PK parameter estimates at steady state following approximately 12 weeks QW administration.
Panel 3 = 50 mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
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.
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration.
Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW
Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 8. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
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.
PK parameter estimates at steady state following approximately 12 weeks QW administration.
Panel 3 = 50 mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
RO7239361 Trough Concentrations
Trough concentrations of RO7239361 at different dose levels.
Panel 1 = 4mg, Panel 2 = 12.5mg and 20mg, Panel 3 = 35mg, Expansion Panels = 35mg and 50mg.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample.
Double-blind phase data for placebo participants is not included. Placebo participants in each arm moved on to RO7239361 upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Serum Concentration of Free Myostatin in the Double-Blind Phase
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Percent Inhibition of Free Myostatin in the Double-Blind Phase
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase
Ratio of contractile vs non-contractile content is contractile content / non-contractile content. Fold change from baseline of the ratio is defined as the ratio of fold change from baseline of contractile content vs fold change from baseline of non-contractile content.
Right thigh measurements. W12 = Week 12, W24 = Week 24.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase
Right thigh measurements. W12 = Week 12, W24 = Week 24.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample.
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Serum Concentration of Free Myostatin, Whole Study
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Percent Inhibition of Free Myostatin, Whole Study
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Serum Concentration of Drug-Myostatin Complex, Whole Study
Participants in the Placebo arm received placebo during the double-blind (DB) period (up to Week 24) and received RO7239361 during the open label (OL) phase. PFS in table row title indicates when study drug was changed from vial to prefilled syringe (PFS).
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02515669
Brief Title
Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
Official Title
A Multi-Site, Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Subcutaneous Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RO7239361 (BMS-986089) in Ambulatory Boys With Duchenne Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
A pre-planned futility analysis indicated lack of efficacy in study NCT03039686 and led to discontinuation of both ongoing studies in DMD.
Study Start Date
December 2, 2015 (Actual)
Primary Completion Date
February 8, 2018 (Actual)
Study Completion Date
April 15, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the safety and tolerability of RO7239361 in boys with Duchenne Muscular Dystrophy with any genetic mutation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy (DMD)
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RO7239361
Arm Type
Active Comparator
Arm Description
RO7239361 subcutaneous injections on specified days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injections on specified days
Intervention Type
Drug
Intervention Name(s)
RO7239361
Other Intervention Name(s)
Anti-Myostatin Adnectin, taldefgrobep alfa
Intervention Description
Colorless to slightly yellow, clear to opalescent solution, essentially free of particulate matter packaged in a 1 cc glass syringe equipped with a safety syringe device.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Colorless to slightly yellow, clear to opalescent solution, essentially free of particulate matter packaged in a 1 cc glass syringe equipped with a safety syringe device.
Primary Outcome Measure Information:
Title
Safety Summary for the 24 Week Double-Blind Phase
Description
Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 24.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline to Week 24
Title
Safety Summary up to Week 72
Description
Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) up to Week 72.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline to Week 72
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses.
Description
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration.
Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361. No participants received the Panel 2 20mg dose.
Time Frame
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
Title
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose.
Description
PK parameter estimates at steady state following approximately 12 weeks QW administration.
Panel 3 = 50 mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Title
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.
Description
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration.
Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW.
Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 6. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Title
Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose.
Description
PK parameter estimates at steady state following approximately 12 weeks QW administration.
Panel 3 = 50 mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Title
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.
Description
PK parameter estimates at steady state. Steady state was achieved following approximately 12 weeks QW administration.
Panel: 1 = 4mg QW, 2 = 12.5mg QW, 3 = 35mg QW
Results for the Panel 3 50mg QW dose level are represented in Outcome Measure 8. Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Title
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.
Description
PK parameter estimates at steady state following approximately 12 weeks QW administration.
Panel 3 = 50 mg QW
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Title
RO7239361 Trough Concentrations
Description
Trough concentrations of RO7239361 at different dose levels.
Panel 1 = 4mg, Panel 2 = 12.5mg and 20mg, Panel 3 = 35mg, Expansion Panels = 35mg and 50mg.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 1: predose, 3, 6, 72 and 96 h postdose; Days 8, 15 and 22: predose; Day 29: predose and 96 h postdose; Weeks 12 and 24: predose
Title
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase
Description
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 8 through Week 24, baseline and on-study information represented in table.
Title
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72
Description
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample.
Double-blind phase data for placebo participants is not included. Placebo participants in each arm moved on to RO7239361 upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 8 through Week 72, baseline and on-study information represented in table.
Title
Serum Concentration of Free Myostatin in the Double-Blind Phase
Description
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 24
Title
Percent Inhibition of Free Myostatin in the Double-Blind Phase
Description
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 24
Title
Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase
Description
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 24
Title
Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase
Description
Ratio of contractile vs non-contractile content is contractile content / non-contractile content. Fold change from baseline of the ratio is defined as the ratio of fold change from baseline of contractile content vs fold change from baseline of non-contractile content.
Right thigh measurements. W12 = Week 12, W24 = Week 24.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 24
Title
Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase
Description
Right thigh measurements. W12 = Week 12, W24 = Week 24.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 24
Title
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study
Description
A positive ADA sample is defined as one in which the presence of detectable ADAs is confirmed to be specific to RO7239361. A participant is considered as ADA positive if, after initiation of treatment, they have an ADA positive relative to baseline sample.
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Day 8 through Week 228, baseline and on-study information represented in table.
Title
Serum Concentration of Free Myostatin, Whole Study
Description
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 252
Title
Percent Inhibition of Free Myostatin, Whole Study
Description
Double-blind phase data for placebo participants are not included in this Whole Study outcome measure, but are reported in the outcome measure specific to the double-blind period. At the end of the double-blind period participants in the placebo arm switched to one of the RO7239361 arms upon entering the open label phase.
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 252
Title
Serum Concentration of Drug-Myostatin Complex, Whole Study
Description
Participants in the Placebo arm received placebo during the double-blind (DB) period (up to Week 24) and received RO7239361 during the open label (OL) phase. PFS in table row title indicates when study drug was changed from vial to prefilled syringe (PFS).
Participants in Panel 1 received 4 mg RO7239361; participants in Panel 2 received either 12.5 mg (weight between 15 and 45 kg) or 20 mg (weight >45 kg) RO7239361, and participants in Panel 3 and the Expansion Panel received either 35 mg (weight between 15 and 45 kg) or 50 mg (weight >45 kg) RO7239361.
Time Frame
Baseline through Week 252
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-6984
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30324
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Saint Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
Children'S Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
12. IPD Sharing Statement
Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting
Learn more about this trial
Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
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