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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02515669
Recruitment Status : Active, not recruiting
First Posted : August 5, 2015
Results First Posted : May 8, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Muscular Dystrophy (DMD) Drug: RO7239361 Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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
Actual Study Start Date : December 2, 2015
Actual Primary Completion Date : February 8, 2018
Estimated Study Completion Date : August 4, 2020


Arm Intervention/treatment
Active Comparator: RO7239361
RO7239361 subcutaneous injections on specified days
Drug: RO7239361
Other Name: Anti-Myostatin Adnectin

Placebo Comparator: Placebo
Placebo subcutaneous injections on specified days
Drug: Placebo



Primary Outcome Measures :
  1. Safety Summary for the 24 Week Double-Blind Phase [ Time Frame: 24 weeks ]

    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.


  2. Safety Summary for the Whole Study [ Time Frame: Baseline to 72 weeks ]

    Percentage of participants with fatalities, adverse event (AEs) and serious adverse events (SAEs) for the whole study.

    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 :
  1. 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: Baseline to Week 24 ]

    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.


  2. Maximum Observed Serum Concentrations (Cmax) of RO7239361 at Steady State for 50 mg QW Dose. [ Time Frame: Baseline to Week 24 ]

    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.


  3. 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: Baseline to Week 24 ]

    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.


  4. Time of Maximum Observed Serum Concentrations (Tmax) of RO7239361 at Steady State for 50 mg QW Dose. [ Time Frame: Baseline to Week 24 ]

    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.


  5. 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: Baseline to Week 24 ]

    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.


  6. 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: Baseline to Week 24 ]

    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.


  7. RO7239361 Trough Concentrations [ Time Frame: Baseline to Week 24 ]

    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.


  8. Frequency of Subjects 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.


  9. Frequency of Subjects With Positive Anti-RO7239361 Antibodies (ADA) Assessment, Whole Study [ 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.


  10. 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.

  11. Percent Inhibition of Free Myostatin [ 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.

  12. Serum Concentration of Drug-myostatin Complex [ 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.

  13. Fold Change From Baseline in Contractile Versus Non-contractile Content for Muscles in the Right Thigh [ 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.


  14. Change From Baseline in Thigh Muscle Maximal Cross Sectional Area (CSAmax) [ 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 10 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02515669


Locations
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United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095-6984
Stanford University
Palo Alto, California, United States, 94305
United States, Florida
University of Florida
Gainesville, Florida, United States, 32607
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30324
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, Missouri
Saint Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, Ontario
Children'S Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Additional Information:
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02515669     History of Changes
Other Study ID Numbers: CN001-006
WN40226 ( Other Identifier: Hoffman-La Roche )
First Posted: August 5, 2015    Key Record Dates
Results First Posted: May 8, 2019
Last Update Posted: August 14, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn