A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral Muscular Dystrophy (FSHD) Clinical Trial

— MANOEUVRE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05548556
• Other study ID #: BN43703
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 7, 2023
• Est. completion date: October 30, 2026

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: October 30, 2026
• Est. primary completion date: May 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ß2-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

Related Conditions & MeSH terms

• Facioscapulohumeral Muscular Dystrophy (FSHD)
• Muscular Dystrophies
• Muscular Dystrophy, Facioscapulohumeral

Intervention

Drug:
• Placebo
Participants will receive subcutaneous (SC) placebo every 4 weeks (Q4W)
• RO7204239
Participants will receive SC RO7204239 Q4W

Locations

Country	Name	City	State
Denmark	Rigshospitalet; Klinik for Nerve- og Muskelsygdomme	København Ø
Italy	ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Centro clinico NEMO (NEuroMuscular Omnicentre)	Milano	Lombardia
Italy	Policlinico Universitario Agostino Gemelli; UOC Neurologia	Roma	Lazio
United Kingdom	National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases	London
United Kingdom	Royal Victoria Infirmary; Clinical Research Facility	Newcastle Upon Tyne
United States	Regents of the University of Colorado	Aurora	Colorado
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	University of Kansas Medical Center; Department of Neurology	Fairway	Kansas
United States	University of Irvine Medical Center (UCIMC); UCI Health Neuromuscular center	Orange	California
United States	Virginia Commonwealth University Medical Center; Department of Neurology	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Denmark,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from baseline in contractile muscle volume (CMV) of quadriceps femoris muscles as assessed by magnetic resonance imaging (MRI) bilaterally		Week 52
Primary	Percentage of participants with adverse events (AEs)		Up to 2.5 years
Secondary	Change from baseline in serum concentration of total latent myostatin		Through 2 years
Secondary	Change from baseline in serum concentration of free latent myostatin		Through 2 years
Secondary	Change from baseline in serum concentration of mature myostatin		Through 2 years
Secondary	Percent change from baseline in CMV of 36 muscles based on whole body MRI		Weeks 28 and 52
Secondary	Change from baseline in fat fraction of 36 muscles based on whole body MRI		Weeks 28 and 52
Secondary	Percent change from baseline in CMV of quadriceps femoris muscles as assessed by MRI bilaterally		Week 28
Secondary	Change from baseline in fat fraction of quadriceps femoris muscles as assessed by MRI bilaterally		Weeks 28 and 52
Secondary	Percent change from baseline in CMV of tibialis anterior muscles as assessed by MRI bilaterally		Weeks 28 and 52
Secondary	Change from baseline in fat fraction of tibialis anterior muscles as assessed by MRI bilaterally		Weeks 28 and 52
Secondary	Percent change from baseline in CMV of biceps brachii muscles as assessed by MRI bilaterally		Weeks 28 and 52
Secondary	Change from baseline in fat fraction of biceps brachii muscles as assessed by MRI bilaterally		Weeks 28 and 52
Secondary	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
Secondary	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
Secondary	Serum concentration of RO7204239		Through 2 years
Secondary	Maximum serum concentration (Cmax) of RO7204239		Through 2 years
Secondary	Area under the concentration-time curve (AUC) of RO7204239		Through 2 years
Secondary	Trough concentration (Ctrough) of RO7204239		Through 2 years
Secondary	Percentage of participants with anti-drug antibodies (ADAs)		Baseline up to approximately 2 years