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

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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

Tracking Information
First Submitted Date  ICMJE July 29, 2015
First Posted Date  ICMJE August 5, 2015
Results First Submitted Date  ICMJE February 7, 2019
Results First Posted Date  ICMJE May 8, 2019
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE December 2, 2015
Actual Primary Completion Date February 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 3, 2015)
  • Safety and Tolerability based on number of incidences of AEs, serious AEs, AEs leading to discontinuation and death, as well as marked treatment emergent abnormalities in clinical laboratory tests [ Time Frame: 24 weeks ]
    Adverse event (AEs)
  • Safety and Tolerability based on number of incidences of vital sign measurements, ECGs, echocardiograms, and physical examinations [ Time Frame: 24 weeks ]
Change History Complete list of historical versions of study NCT02515669 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2015)
  • Trough concentrations of BMS-986089 [ Time Frame: Day 8 through Week 24 ]
  • Maximum observed concentration (Cmax) of BMS-986089 [ Time Frame: Day 1 and 29 ]
  • Frequency of subjects with positive anti-BMS-986089 antibodies (ADA) assessment [ Time Frame: Day 8 through Week 24 ]
  • Frequency of subjects who develop positive ADA following a negative baseline [ Time Frame: Day 8 through Week 24 ]
  • Anti-BMS-986089 antibodies on selected days [ Time Frame: Day 8 through Week 24 ]
  • Serum concentration of free myostatin [ Time Frame: Day 8 through Week 24 ]
  • Change from baseline in volume of thigh muscle contractile and non-contractile tissue [ Time Frame: Day 8 through Week 24 ]
  • Change from baseline in thigh muscle lipid fraction [ Time Frame: Day 8 through Week 24 ]
  • Change from baseline in thigh muscle maximal cross sectional area [ Time Frame: Day 8 through Week 24 ]
  • Serum Concentration of Drug-myostatin Complex [ Time Frame: Day 8 through Week 24 ]
  • Serum concentration of percent inhibition of free myostatin at trough [ Time Frame: Day 8 through Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Muscular Dystrophy (DMD)
Intervention  ICMJE
  • Drug: RO7239361
    Other Name: Anti-Myostatin Adnectin
  • Drug: Placebo
Study Arms  ICMJE
  • Active Comparator: RO7239361
    RO7239361 subcutaneous injections on specified days
    Intervention: Drug: RO7239361
  • Placebo Comparator: Placebo
    Placebo subcutaneous injections on specified days
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 10, 2018)
43
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2015)
40
Estimated Study Completion Date  ICMJE August 4, 2020
Actual Primary Completion Date February 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 5 Years to 10 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02515669
Other Study ID Numbers  ICMJE CN001-006
WN40226 ( 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  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP