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

• ClinicalTrials.gov Identifier: NCT05548556
• Recruitment Status: Active, not recruiting
• First Posted: September 21, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Facioscapulohumeral Muscular Dystrophy (FSHD)	Drug: Placebo; Drug: RO7204239	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 7, 2023
• Estimated Primary Completion Date: May 2, 2025
• Estimated Study Completion Date: October 30, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change from baseline in serum concentration of total latent myostatin [ Time Frame: Through 2 years ]
2. Change from baseline in serum concentration of free latent myostatin [ Time Frame: Through 2 years ]
3. Change from baseline in serum concentration of mature myostatin [ Time Frame: Through 2 years ]
4. Percent change from baseline in CMV of 36 muscles based on whole body MRI [ Time Frame: Weeks 28 and 52 ]
5. Change from baseline in fat fraction of 36 muscles based on whole body MRI [ Time Frame: Weeks 28 and 52 ]
6. Percent change from baseline in CMV of quadriceps femoris muscles as assessed by MRI bilaterally [ Time Frame: Week 28 ]
7. Change from baseline in fat fraction of quadriceps femoris muscles as assessed by MRI bilaterally [ Time Frame: Weeks 28 and 52 ]
8. Percent change from baseline in CMV of tibialis anterior muscles as assessed by MRI bilaterally [ Time Frame: Weeks 28 and 52 ]
9. Change from baseline in fat fraction of tibialis anterior muscles as assessed by MRI bilaterally [ Time Frame: Weeks 28 and 52 ]
10. Percent change from baseline in CMV of biceps brachii muscles as assessed by MRI bilaterally [ Time Frame: Weeks 28 and 52 ]
11. Change from baseline in fat fraction of biceps brachii muscles as assessed by MRI bilaterally [ Time Frame: Weeks 28 and 52 ]
12. Percent change from baseline in contractile cross-sectional area (CSA) of skeletal muscle in the proximal lower limb muscles as assessed by MRI bilaterally [ Time Frame: Weeks 28 and 52 ]
13. Change from baseline in fat fraction of proximal lower limb muscles as assessed at a single mid-femur slice bilaterally by MRI [ Time Frame: Weeks 28 and 52 ]
14. Serum concentration of RO7204239 [ Time Frame: Through 2 years ]
15. Maximum serum concentration (Cmax) of RO7204239 [ Time Frame: Through 2 years ]
16. Area under the concentration-time curve (AUC) of RO7204239 [ Time Frame: Through 2 years ]
17. Trough concentration (Ctrough) of RO7204239 [ Time Frame: Through 2 years ]
18. Percentage of participants with anti-drug antibodies (ADAs) [ Time Frame: Baseline up to approximately 2 years ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of Irvine Medical Center (UCIMC); UCI Health Neuromuscular center

Orange, California, United States, 92868

United States, Colorado

Regents of the University of Colorado

Aurora, Colorado, United States, 80045

United States, Kansas

University of Kansas Medical Center; Department of Neurology

Fairway, Kansas, United States, 66205

United States, Maryland

Kennedy Krieger Institute

Baltimore, Maryland, United States, 21205

United States, Virginia

Virginia Commonwealth University Medical Center; Department of Neurology

Richmond, Virginia, United States, 23298-0599

Denmark

Rigshospitalet; Klinik for Nerve- og Muskelsygdomme

København Ø, Denmark, 2100

Italy

Policlinico Universitario Agostino Gemelli; UOC Neurologia

Roma, Lazio, Italy, 00168

ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Centro clinico NEMO (NEuroMuscular Omnicentre)

Milano, Lombardia, Italy, 20162

United Kingdom

National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases

London, United Kingdom, WC1N 3BG

Royal Victoria Infirmary; Clinical Research Facility

Newcastle Upon Tyne, United Kingdom, NE1 4LP

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT05548556
• Other Study ID Numbers: BN43703
• First Posted: September 21, 2022
• Last Update Posted: April 24, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Facioscapulohumeral; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn