Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD

Facioscapulohumeral Muscular Dystrophy Clinical Trial

Official title:

Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03458832
• Other study ID #: STUDY00140842
• Secondary ID: U01NS101944
• Status: Active, not recruiting
• Start date: March 5, 2018
• Est. completion date: March 2023

Study information

• Verified date: September 2021
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 and optimize eligibility criteria by testing 160 patients in 7 sites over a period of 24 months.

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 (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, 24 months study of 160 subjects.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: March 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Facioscapulohumeral Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Facioscapulohumeral

Intervention

Diagnostic Test:
• FSHD-specific functional rating scale
The FSHD-COM is composed of disease-relevant functional tasks such as leg function; shoulder and arm function; trunk function, hand function, and balance.

Device:
• Electrical Impedance Myography
EIM is a non-invasive, painless, and fast technique for obtaining information on how a patient's muscle structure is changing. EIM uses a small electrical current to measure the health of the underlying muscle. The patient will be asked to lie down and a trained clinical evaluator will perform testing on 16 total muscles (8 on each side) on your arms and legs.

Locations

Country	Name	City	State
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	The Ohio State University	Columbus	Ohio
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California Los Angeles	Los Angeles	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Utah	Salt Lake City	Utah
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Kansas Medical Center	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Validate FSHD-COM as COA	The FSHD-COM is an 18-item evaluator-administered instrument comprised of individually validated functional motor tasks. The body regions represented match areas of importance identified by patients and include: leg function; shoulder and arm function; trunk function, hand function; and balance. Each item is scored on a 0-4 scale, with 0 representing unaffected/normal performance, and the divisions based on healthy population normative values, or the relative degree of ability to perform the functional task. The total scale has 72 points, with larger weight given to the two most frequently patient-cited areas of functional motor concern - leg function and shoulder and arm function.	24 Months
Primary	Validate EIM as COA		24 Months
Secondary	Motor Function Measure (MFM) Domain 1	The MFM domain 1 is a validated evaluator administered functional measure for neuromuscular disorders, with 13 items related to standing and transfers.	24 Months
Secondary	Facial Function	The Iowa Oral Performance Instrument (IOPI) is a means to quantify lip, tongue, and buccal strength using a validated tool with published ranges for normative data for lingual measurements.	24 Months
Secondary	Reachable Workspace	Subjects are seated in front of a 3D camera and asked to perform a standardized upper extremity movement protocol under the supervision of a study clinical evaluator.	24 Months
Secondary	Manual Muscle Testing	Strength testing will be performed using manual muscle testing (MMT) using a hand held force dynamometer.	24 Months
Secondary	Respiratory Function	The researchers will obtain forced vital capacity and forced expiratory volume in 1 second using bedside spirometry.	24 Months
Secondary	Whole body and regional lean muscle mass (LMM)	Whole body and regional lean muscle mass (LMM) will be measured via Dual Energy X-Ray Absorptiometry (DEXA).	24 Months
Secondary	Severity Scores	A limited physical exam and strength testing will be used to derive two FSHD clinical severity scores. These severity scores both rank weakness in the face, shoulders, arms, distal, and proximal lower extremities on either a 10 or 15 point scale.	24 Months
Secondary	FSHD-Health Inventory (HI)	The HI is a 15 domain questionnaire designed and based on patient interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. 116 questions are combined into a total score, the score is transformed onto a percentage scale, with 100 representing maximal disability, and lower scores representing decreasing disability.	24 Months
Secondary	Patient-Reported Outcomes Measurement Information System-57 (PROMIS57)	The PROMIS57 is an instrument developed by the NIH which generates scores for physical function, and the impact of physical limitations on daily life. 57 questions are summed into a total score, which is transformed into a normalized t-score with 50 representing normal, and lower scores representing increasing disability.	24 Months
Secondary	The Upper Extremity Functional Index	This index measures upper extremity dysfunction. 20 questions are combined into a total score, the score is transformed into a normalized score with 80 representing normal, and lower scores representing increasing disability.	24 Months
Secondary	The Facial Disability Index (FDI)	The FDI is a short 5 item questionnaire. The five questions are summed into total score which transformed onto a percentage scale, with 100 representing normal, and lower scores representing increasing disability.	24 Months
Secondary	Fall assessment	Fall assessment will be completed weekly for 3 months after the month 3 visit.	Total between Month 3 and Month 6 Visit
Secondary	Quantitative myometry	Force will be measured on digital myometer, in KG-force.	24 Months