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

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2016-001654-18-DE
• Date of registration: 23/06/2017
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy
• Scientific title: A randomized, double blind, placebo-controlled, study to assess the efficacy, safety, and tolerability of RO7239361 in ambulatory boys with Duchenne Muscular dystrophy
• Date of first enrolment: 13/11/2017
• Target sample size: 159
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001654-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Canada, France, Germany, Italy, Japan, Netherlands, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Key Inclusion Criteria:
• Males, 6 >= to < 12 years of age at time of randomization.
• Diagnosis of DMD, confirmed by medical history (eg., onset of clinical signs or symptoms before 5 years of age together with an elevated serum creatine kinase level observed before or after initial diagnosis) and by genotyping.
• Participants >= 15 kg.
• Ambulatory without assistance.
• Participants must be receiving corticosteroids (CS, prednisone, prednisolone, or deflazacort) for at least 6 months prior to the start of study drug, with no significant change in dosage (> 0.2 mg/kg prednisone or > 0.24 mg/kg deflazacort) or dosing regimen for at least 12 weeks prior to the start of study drug, with the expectation that dosage and dosing regimen will not change significantly for the duration of the study.
• North Star Ambulatory Assessment (NSAA) score >=15 points at screening.
• 4SC<= 8 seconds at screening.
• Subjects must agree to avoid major changes in their physical or respiratory therapy regimen during the double blind phase, to the extent possible.
• Subjects who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) plus 5 half-lives of the study treatment [RO7239361; 50 days] plus 90 days (duration of sperm turnover) for a total of 140 days (5 months) post-treatment completion.
For the rest of Inclusion Criteria, please refer to study protocol Section 6.1 (page 50).
Are the trial subjects under 18? yes
Number of subjects for this age range: 159
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Key Exclusion Criteria:
• Participants with cognitive impairment or behavioral issues that, in the judgement of the investigator, will compromise their ability to comply with study procedures.
• Participants on intermittent CS regimens with off periods of 20 days or longer (eg.: 10 days on, 20 days off).
• Any change (initiation, change in drug class, dose modification unrelated to change in body weight, interruption or re-initiation) in prophylaxis /treatment for congestive heart failure (CHF) within 12 weeks prior to start of study treatment.
• Any change (initiation, change in drug class, dose modification unrelated to change in body weight, interruption or re-initiation) in prophylaxis/treatment for bone density within 12 weeks prior to start of study treatment.
• Treatment with exon skipping therapies within 6 months prior to the start of study drug administration.
• Treatment with ataluren currently or within 12 weeks prior to the start of study drug administration.
• Treatment with any other investigational drug (excluding deflazacort in CS dose-finding trials) currently or within 12 weeks prior to the start of study drug administration.
• Concurrent or previous participation at any time in a gene therapy study.
• Participants with a FVC of < 50% of predicted value (in participants able to produce a valid FVC, as judged by the clinical evaluator or respiratory therapist).
• Cutaneous AEs sustained during participation in a prior clinical trial that resolved less than 12 weeks prior to the start of study drug administration.
• Current or prior treatment within 12 weeks prior to the start of study drug administration with androgens or human growth hormone.
• Prior treatment with RO7239361 or any other anti-myostatin agent.
• History of lower limb fracture within 12 weeks prior to the start of study drug administration.
• History of upper limb fracture within 8 weeks prior to the start of study drug administration.
• Any injury that may impact functional testing. Previous injuries must be fully healed prior to consenting.
• Expectation of major surgical procedure, such as scoliosis surgery, during the double blind phase of this study.
• Requirement of daytime ventilator assistance.
• Initiation of nighttime ventilation less than 4 weeks prior to the start of study drug administration.
• Expectation that daytime or nighttime ventilation may be initiated during the double blind phase of this study.
• Clinical signs or symptoms of uncontrolled congestive heart failure (CHF) (American College of Cardiology/American Heart Associated Stage C or Stage D).
• For participants participating in cMRI substudy: implanted ferromagnetic metal (implanted metal that is not ferromagnetic, such as surgical steel or titanium implants may be allowed if the implants will not compromise the quality of the cMRI).
• History of hypersensitivity to components of the study drug (histidine, trehalose, diethylenetriaminepentaacetic acid, polysorbate 80).
• Unwilling or unable to administer study drug at home.
For the rest of Exclusion Criteria, please refer to study protocol Section 6.2 (page 51).


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Duchenne Muscular Dystrophy
MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: RO7239361 Injections, 7.5 mg/Syringe (10.7 mg/mL)
Product Code: RO7239361
Pharmaceutical Form: Injection
INN or Proposed INN: Anti-myostatin Adnectin
Current Sponsor code: RO7239361
Other descriptive name: BMS-986089-01, anti-myostatin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10.7-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: RO7239361 Injections, 15 mg/Syringe (21.4 mg/mL)
Product Code: RO7239361
Pharmaceutical Form: Injection
INN or Proposed INN: Anti-myostatin Adnectin
Current Sponsor code: RO7239361
Other descriptive name: BMS-986089-01, anti-myostatin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 21.4-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: RO7239361 Injections, 35 mg/Syringe (50 mg/mL)
Product Code: RO7239361
Pharmaceutical Form: Injection
INN or Proposed INN: Anti-myostatin Adnectin
Current Sponsor code: RO7239361
Other descriptive name: BMS-986089-01, anti-myostatin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: RO7239361 Injections, 50 mg/Syringe (71.4 mg/mL)
Product Code: RO7239361
Pharmaceutical Form: Injection
INN or Proposed INN: Anti-myostatin Adnectin
Current Sponsor code: RO7239361
Other descriptive name: BMS-986089-01, anti-myostatin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 71.4-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 1, week 12, week 24, week 36 and week 48 during double blind phase.
Week 1, week 12, week 24, week 36 and week 48 during open label phase.

Main Objective: To compare the efficacy of RO7239361 to placebo in ambulatory boys with Duchenne muscular dystrophy

Primary end point(s): The change from baseline in the North Star Ambulatory Assessment (NSAA) total score at Week 48 in RO723936-treated participants compared to placebo-treated participants.

Secondary Objective: • To compare the efficacy of RO7239361 to placebo using the following tests:
- 4 stair climb velocity (4SCV)
- Stand from supine velocity
- 10 M walk/run velocity
- PODCI transfers and basic mobility subscale
- Proximal lower extremity flexor (knee extension and knee flexion)
strength, measured using manual myometry
- 6 Minute Walk Distance (6MWD)
- Clinical Global Impression of Change (CGI-C)
- Stride velocity recorded with ActiMyo
• To assess the safety and tolerability of RO7239361 in boys with DMD as reflected by new or worsening lab abnormalities (as defined by CTCAE criteria), serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation.

Secondary Outcome(s)

Secondary end point(s): • Change from baseline at Week 48 in RO7239361-treated participants
compared to placebo-treated participants in the following:
- 4 stair climb velocity (4SCV)
- Stand from supine velocity
- 10 M walk/run velocity
- PODCI transfers and basic mobility subscale
- Proximal lower extremity flexor (knee extension and knee flexion) strength, measured using manual myometry
- 6-Minute Walk Distance (6MWD)
- Clinical Global Impression of Change (CGI-C)
- 95th percentile stride velocity, as recorded with ActiMyo in a subset of
the overall study population
• Tabulations of the numbers of unique participants with new or worsening laboratory abnormalities, SAEs and AEs leading to discontinuation, in RO7239361 arms compared to the placebo arm.

Timepoint(s) of evaluation of this end point: Day 1, week 12, week 24, week 36 and week 48 during double blind phase.
Week 1, week 12, week 24, week 36 and week 48 during open label phase.

Secondary ID(s)

2016-001654-18-SE

WN40227

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date:
Contact: