A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (MANOEUVRE)

A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Pharmacodynamics, Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy

The purpose of this study is to evaluate the pharmacodynamics, safety, tolerability, pharmacokinetics, and efficacy of RO7204239, a humanized monoclonal antibody that binds to human latent myostatin, in ambulant adult participants with facioscapulohumeral muscular dystrophy (FSHD).

Study Overview

• Status: Active, not recruiting
• Conditions: Facioscapulohumeral Muscular Dystrophy (FSHD)
• Intervention / Treatment: Drug: Placebo; Drug: RO7204239

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
  • Lombardy
    • Milan, Lombardy, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • National Hospital for Neurology and Neurosurgery,
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
• United States
  • California
    • Orange, California, United States, 92868
      • University of Irvine Medical Center (UCIMC)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Regents of the University of Colorado
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Genetic confirmation of FSHD1 or FSHD2
• Clinical findings consistent with FSHD
• Ability to walk unassisted
• Ricci Clinical Severity Scale score ≥ 2.5 and ≤ 4
• Agreement to maintain the same frequency and intensity of physiotherapy, occupational therapy, and other forms of exercise during the clinical study

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 17 months after the final dose of RO7204239
• Current or previous treatment (or receipt) of anti-myostatin therapies
• Treatment with any investigational therapy within 90 days prior to screening, or 5 drug-elimination half-lives of the drug, whichever is longer
• Contraindications to MRI scans
• Presence of clinically significant ECG abnormalities
• Presence of clinically significant cardiovascular disease
• Presence of clinically significant abnormal findings in echocardiography at screening, with the exception of mitral valve prolapse, which does not exclude participants from the study
• Any major illness within 1 month before screening
• Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to RO7204239, or to the constituents of its formulation
• History of malignancy (except in situ basal cell carcinoma of the skin and in situ carcinoma of the cervix of the uterus that have been excised and resolved with documented clean margins on pathology)
• Any clinically relevant history of anaphylactic reaction requiring inotropic support
• Any abnormal skin conditions, pigmentation, or lesions in the area intended for SC injection (abdomen) and that would prevent visualization of potential injection-site reactions to RO7204239
• Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening or longer, if judged by the investigator that it may affect motor function assessment
• Any planned surgery that may affect a participant's motor function assessment, including participants who have had surgery of scapular fixation within the 12 months preceding screening or that are planned during the study
• Use of the following medications within 90 days prior to enrollment: salbutamol or another β2-adrenergic agonist taken orally; creatine; recombinant human growth hormone; recombinant human insulin growth factor-1; testosterone, oxandrolone, or other anabolic steroid; chronic oral or parenteral use of corticosteroids (inhaled corticosteroid use is allowed) unless required to manage injection reactions;agents anticipated to increase or decrease muscle volume or strength

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will complete a 4-week pre-treatment period to collect baseline movement data with a wearable device, then receive subcutaneous (SC) placebo every 4 weeks for 52 weeks. After the treatment period, participants will have the option to receive RO7204239 for an additional 52 weeks.	Drug: Placebo; Participants will receive subcutaneous (SC) placebo every 4 weeks (Q4W)
Experimental: RO7204239; Participants will complete a 4-week pre-treatment period to collect baseline movement data with a wearable device, then receive SC RO7204239 every 4 weeks for 52 weeks. After the treatment period, participants will have the option to receive RO7204239 for an additional 52 weeks.	Drug: RO7204239; Participants will receive SC RO7204239 Q4W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in contractile muscle volume (CMV) of quadriceps femoris muscles as assessed by magnetic resonance imaging (MRI) bilaterally	Week 52
Percentage of participants with adverse events (AEs)	Up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in serum concentration of total latent myostatin	Through 2 years
Change from baseline in serum concentration of free latent myostatin	Through 2 years
Change from baseline in serum concentration of mature myostatin	Through 2 years
Percent change from baseline in CMV of 36 muscles based on whole body MRI	Weeks 28 and 52
Change from baseline in fat fraction of 36 muscles based on whole body MRI	Weeks 28 and 52
Percent change from baseline in CMV of quadriceps femoris muscles as assessed by MRI bilaterally	Week 28
Change from baseline in fat fraction of quadriceps femoris muscles as assessed by MRI bilaterally	Weeks 28 and 52
Percent change from baseline in CMV of tibialis anterior muscles as assessed by MRI bilaterally	Weeks 28 and 52
Change from baseline in fat fraction of tibialis anterior muscles as assessed by MRI bilaterally	Weeks 28 and 52
Percent change from baseline in CMV of biceps brachii muscles as assessed by MRI bilaterally	Weeks 28 and 52
Change from baseline in fat fraction of biceps brachii muscles as assessed by MRI bilaterally	Weeks 28 and 52
Percent change from baseline in contractile cross-sectional area (CSA) of skeletal muscle in the proximal lower limb muscles as assessed by MRI bilaterally	Weeks 28 and 52
Change from baseline in fat fraction of proximal lower limb muscles as assessed at a single mid-femur slice bilaterally by MRI	Weeks 28 and 52
Serum concentration of RO7204239	Through 2 years
Maximum serum concentration (Cmax) of RO7204239	Through 2 years
Area under the concentration-time curve (AUC) of RO7204239	Through 2 years
Trough concentration (Ctrough) of RO7204239	Through 2 years
Percentage of participants with anti-drug antibodies (ADAs)	Baseline up to approximately 2 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Actual): May 2, 2025
• Study Completion (Estimated): October 23, 2026

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Facioscapulohumeral
• Other Study ID Numbers: BN43703

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No