Clinical trial NCT05548556: A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Facioscapulohumeral Muscular Dystrophy (FSHD)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-09-21
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Percent change from baseline in contractile muscle volume (CMV) of quadriceps femoris muscles as assessed by magnetic resonance imaging (MRI) bilaterally
timeFrame: Week 52
measure: Percentage of participants with adverse events (AEs)
timeFrame: Up to 2.5 years
Secondary outcomes:
measure: Change from baseline in serum concentration of total latent myostatin
timeFrame: Through 2 years
measure: Change from baseline in serum concentration of free latent myostatin
timeFrame: Through 2 years
measure: Change from baseline in serum concentration of mature myostatin
timeFrame: Through 2 years
measure: Percent change from baseline in CMV of 36 muscles based on whole body MRI
timeFrame: Weeks 28 and 52
measure: Change from baseline in fat fraction of 36 muscles based on whole body MRI
timeFrame: Weeks 28 and 52
measure: Percent change from baseline in CMV of quadriceps femoris muscles as assessed by MRI bilaterally
timeFrame: Week 28
measure: Change from baseline in fat fraction of quadriceps femoris muscles as assessed by MRI bilaterally
timeFrame: Weeks 28 and 52
measure: Percent change from baseline in CMV of tibialis anterior muscles as assessed by MRI bilaterally
timeFrame: Weeks 28 and 52
measure: Change from baseline in fat fraction of tibialis anterior muscles as assessed by MRI bilaterally
timeFrame: Weeks 28 and 52
measure: Percent change from baseline in CMV of biceps brachii muscles as assessed by MRI bilaterally
timeFrame: Weeks 28 and 52
measure: Change from baseline in fat fraction of biceps brachii muscles as assessed by MRI bilaterally
timeFrame: Weeks 28 and 52
measure: Percent change from baseline in contractile cross-sectional area (CSA) of skeletal muscle in the proximal lower limb muscles as assessed by MRI bilaterally
timeFrame: Weeks 28 and 52
measure: Change from baseline in fat fraction of proximal lower limb muscles as assessed at a single mid-femur slice bilaterally by MRI
timeFrame: Weeks 28 and 52
measure: Serum concentration of RO7204239
timeFrame: Through 2 years
measure: Maximum serum concentration (Cmax) of RO7204239
timeFrame: Through 2 years
measure: Area under the concentration-time curve (AUC) of RO7204239
timeFrame: Through 2 years
measure: Trough concentration (Ctrough) of RO7204239
timeFrame: Through 2 years
measure: Percentage of participants with anti-drug antibodies (ADAs)
timeFrame: Baseline up to approximately 2 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of Irvine Medical Center (UCIMC)
state: California
city: Aurora
country: United States
facility: Regents of the University of Colorado
state: Colorado
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery,
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: