Clinical Trial Readiness Network FSHD France: Prospective 24 Months MRI Study

Clinical Trial Readiness Network FSHD France: Prospective 24 Months MRI Study

The overall aim of this study is to hasten drug development for facioscapulohumeral muscular dystrophy (FSHD). Recent breakthroughs in FSHD research have identified the primary disease mechanism as the aberrant expression of a normally silenced gene, DUX4, resulting in a toxic gain-of-function. This disease mechanism is particularly amenable to knock-down of DUX4 using epigenetic strategies or RNA therapies, as well as to other interventions targeting the downstream effects of DUX4 expression. There are many drug companies actively working towards disease-targeted therapies, and two clinical trials either under way now, or planned to start in early Fall 2016. However, meetings with industry, advocacy groups, and FSHD researchers have identified several gaps in the clinical trial arsenal, and clinical trial planning as a major goal for the community. Consequently, there is an urgent need to establish the tools necessary for the conduct of currently planned and expected therapeutic trials in FSHD.

To this end, the researchers propose to develop two novel clinical outcome assessments (COA), a composite functional outcome measure (FSH-COM) and skeletal muscle biomarker, electrical impedance myography (EIM). In addition there is broad consensus a better understanding of the relationship of genetic and demographic features to disease progression will be necessary for enumerating eligibility criteria.

The specific aims are to: 1. Determine the multi-site validity of the COAs, 2. Compare the responsiveness of new COAs to other FSHD outcomes and determine the minimal clinically meaningful changes, and 3. establish FSHD cohort characteristics useful for determining clinical trial eligibility criteria. To achieve these aims, the Nice University Hospital is conducting a monocentric, prospective, 18 month study on 30 subjects.

Inclusion Criteria

• Genetically confirmed FSHD1 or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring 63
• Age 18-75 years
• Symptomatic limb weakness
• Patient able to walk alone or with a walking aid.
• Manual Muscle Testing (MMT) score ≥ 4 for one of the lower limb muscles
• Patient affiliated to the social security system
• Patient giving written consent after written and oral information.
• If taking over the counter supplements willing to remain consistent with supplement regimen throughout the course of the study

Exclusion Criteria

• Cardiac or respiratory dysfunction (deemed clinically unstable, or would interfere with safe testing in the opinion of the Investigator)
• Orthopedic conditions that preclude safe testing of muscle function
• Regular use of available muscle anabolic/catabolic agents such as corticosteroids, oral testosterone or derivatives, or oral beta agonists
• Use of an experimental drug in an FSHD clinical trial within the past 30 days
• Pregnancy.
• Contraindication for muscle MRI
• Any major comorbidity