Clinical trial NCT03458832: Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD
Official title: Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Facioscapulohumeral Muscular Dystrophy
Keywords: muscular dystrophy.
FSHD
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: FSHD Society
name: Friends Research Institute, Inc.
name: Muscular Dystrophy Association
name: AFM Telethon
name: University of Rochester
name: Leiden University Medical Center
name: Dyne Therapeutics
First posted: 2018-03-08
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with FSHD that are seen in the researchers clinic.

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: FSHD composite (FSHD-COM)
timeFrame: 24 Months
measure: Electrical Impedance Myography (EIM)
timeFrame: 24 Months
Secondary outcomes:
measure: Motor Function Measure (MFM) Domain 1
timeFrame: 24 Months
measure: Facial Function
timeFrame: 24 Months
measure: Reachable Workspace (RWS)
timeFrame: 24 Months
measure: Manual Muscle Testing (MMT)
timeFrame: 24 Months
measure: Force Vital Capacity (FVC)
timeFrame: 24 Months
measure: Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP)
timeFrame: 24 Months
measure: Whole body and regional lean muscle mass (LMM)
timeFrame: 24 Months
measure: Severity Scores
timeFrame: 24 Months
measure: FSHD-Health Inventory (HI)
timeFrame: 24 Months
measure: Patient-Reported Outcomes Measurement Information System-57 (PROMIS57)
timeFrame: 24 Months
measure: The Upper Extremity Functional Index
timeFrame: 24 Months
measure: The Facial Disability Index (FDI)
timeFrame: 24 Months
measure: Fall assessment
timeFrame: Total between Month 3 and Month 6 Visit
measure: Domain Delta Anchor
timeFrame: 24 Months
measure: Quantitative myometry (QMA)
timeFrame: 24 Months
measure: Muscle Biopsy
timeFrame: 24 Months
measure: Blood biomarkers
timeFrame: 24-Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Nice
country: France
facility: Chu De Nice
city: Paris
country: France
facility: Institut de Myologie
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München
city: Milano
country: Italy
facility: Centro Clinico NeMO
city: Nijmegen
country: Netherlands
facility: Radboud Unviersity
city: London
country: United Kingdom
facility: University of College London - Queens Square
Study officials:
affiliation: University of Kansas Medical Center
name: Jeffrey Statland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Rabi Tawil, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: LoRusso S, Johnson NE, McDermott MP, Eichinger K, Butterfield RJ, Carraro E, Higgs K, Lewis L, Mul K, Sacconi S, Sansone VA, Shieh P, van Engelen B, Wagner K, Wang L, Statland JM, Tawil R; ReSolve Investigators and the FSHD CTRN18. Clinical trial readiness to solve barriers to drug development in FSHD (ReSolve): protocol of a large, international, multi-center prospective study. BMC Neurol. 2019 Sep 10;19(1):224. doi: 10.1186/s12883-019-1452-x.