Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD

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 researchers are conducting a
multicenter, prospective, 18 months study of 160 subjects.

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