Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD

October 13, 2020 updated by: Hoffmann-La Roche

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

The purpose of this study is to determine the safety and tolerability of RO7239361 in boys with Duchenne Muscular Dystrophy with any genetic mutation.

Study Overview

Status

Terminated

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
    • California
      • Los Angeles, California, United States, 90095-6984
        • David Geffen School of Medicine at UCLA
      • Palo Alto, California, United States, 94305
        • Stanford University
    • Florida
      • Gainesville, Florida, United States, 32607
        • University of Florida
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30324
        • Children's Healthcare of Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Kennedy Krieger Institute
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Saint Louis Children's Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: RO7239361
RO7239361 subcutaneous injections on specified days
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.
Other Names:
  • Anti-Myostatin Adnectin
  • taldefgrobep alfa
Placebo Comparator: Placebo
Placebo subcutaneous injections on specified days
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Summary for the 24 Week Double-Blind Phase
Time Frame: Baseline to Week 24

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.

Baseline to Week 24
Safety Summary up to Week 72
Time Frame: Baseline 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.

Baseline to Week 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 4 mg QW, 12.5 mg QW and 35 mg QW Doses.
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

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.

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
Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose.
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

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.

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
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 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

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.

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
Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose.
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

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.

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
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.
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

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.

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
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.
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

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.

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
RO7239361 Trough Concentrations
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

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.

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
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Double-Blind Phase
Time Frame: Day 8 through Week 24, baseline and on-study information represented in table.

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.

Day 8 through Week 24, baseline and on-study information represented in table.
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment up to Week 72
Time Frame: Day 8 through Week 72, baseline and on-study information represented in table.

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.

Day 8 through Week 72, baseline and on-study information represented in table.
Serum Concentration of Free Myostatin in the Double-Blind Phase
Time Frame: Baseline through 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.
Baseline through Week 24
Percent Inhibition of Free Myostatin in the Double-Blind Phase
Time Frame: Baseline through 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.
Baseline through Week 24
Serum Concentration of Drug-Myostatin Complex in the Double-Blind Phase
Time Frame: Baseline through 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.
Baseline through Week 24
Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh in the Double-Blind Phase
Time Frame: Baseline through Week 24

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.

Baseline through Week 24
Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) in the Double-Blind Phase
Time Frame: Baseline through Week 24

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.

Baseline through Week 24
Percentage of Participants With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study
Time Frame: Day 8 through Week 228, baseline and on-study information represented in table.

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.

Day 8 through Week 228, baseline and on-study information represented in table.
Serum Concentration of Free Myostatin, Whole Study
Time Frame: Baseline through Week 252

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.

Baseline through Week 252
Percent Inhibition of Free Myostatin, Whole Study
Time Frame: Baseline through Week 252

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.

Baseline through Week 252
Serum Concentration of Drug-Myostatin Complex, Whole Study
Time Frame: Baseline through Week 252

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.

Baseline through Week 252

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 2, 2015

Primary Completion (Actual)

February 8, 2018

Study Completion (Actual)

April 15, 2020

Study Registration Dates

First Submitted

July 29, 2015

First Submitted That Met QC Criteria

August 3, 2015

First Posted (Estimate)

August 5, 2015

Study Record Updates

Last Update Posted (Actual)

November 4, 2020

Last Update Submitted That Met QC Criteria

October 13, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • CN001-006
  • WN40226 (Other Identifier: Hoffman-La Roche)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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