Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD

The primary cause of facioscapulohumeral muscular dystrophy (FSHD), a common adult-onset dystrophy, was recently discovered identifying targets for therapy. As multiple drug companies pursue treatments for FSHD, there is an urgent need to define the clinical trial strategies which will hasten drug development, including creating disease-relevant outcome measures and optimizing inclusion criteria. This proposal will develop two new outcome measures (FSHD-COM and EIM) and optimize eligibility criteria by testing 320 patients across 14 international sites over a period of 24 months.

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 (FSHD-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 researchers are conducting a multicenter, prospective, 24 months study of 320 subjects.

Eligibility Criteria:
Inclusion Criteria:

* Patients with genetically confirmed FSHD1 or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring
* Patients with symptomatic limb weakness
* Patients must be able to walk 30 feet without the support of another person or assistance (canes, walking sticks, and braces allowed; no walker).
* If taking over the counter supplements, willing to remain consistent with supplement regimen throughout the course of the study

Exclusion Criteria:

* Patients with cardiac or respiratory dysfunction (deemed clinically unstable, or would interfere with safe testing, in the opinion of the Investigator)
* Patients with orthopedic conditions that preclude safe testing of muscle function
* Patients that regularly use available muscle anabolic/catabolic agents such as corticosteroids, oral testosterone or derivatives, or oral beta agonists
* Patients that have used an experimental drug in an FSHD clinical trial within the past 30 days
* Patients that are pregnant