Clinical trial NCT06721299: Clenbuterol to Target DUX4 in FSHD
Official title: Clenbuterol to Target DUX4 in FSHD (Target FSHD): Open Label Safety and Tolerability Study of 3 Doses of Clenbuterol
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Muscular Dystrophy, Facioscapulohumeral
Keywords: FSHD
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: University of Washington
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: University of Rochester
First posted: 2024-12-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Three sequential multiple ascending dose cohorts (of n=10 participants)
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if Clenbuterol is a therapeutic option for FSHD by determining the safety and tolerability of the medication at three different dose levels.

Detailed description: Clenbuterol is an EMA approved drug for COPD that three independent patient derived screens identified as suppressing DUX4 expression in cultured FSHD muscle. Prior clinical studies with related beta2-agonists showed some activity in FSHD but did not meet their primary endpoint, although the prior studies would likely have been designed differently with current knowledge. Target FSHD is a 6-month open-label multiple ascending dose study of clenbuterol for safety and tolerability to determine the best dose for a future trial of efficacy. In addition, this study will collect secondary outcome data on muscle function, MRI changes (lean muscle volume, fat infiltration, STIR-rating) and molecular markers of disease activity (histopathology and pre-determined baskets of DUX4-target, inflammation, and ECM genes) at the beginning and end of the study to assess and power their utility as measures of drug activity in a future interventional study of efficacy.

Eligibility criteria: Inclusion Criteria:

* Genetically confirmed diagnosis of FSHD type 1 or 2, or have a clinical diagnosis of FSHD type 1 with a first degree relative with confirmed mutation
* between 18 and 75 years of age
* with a clinical severity score between 1 and 4
* Able to walk 30ft without support of another person
* Showing anti-gravity strength on at least one of the tibialis anterior muscles or having an MRI eligible muscle in the leg for needle biopsy
* willing and able to provide informed consent

Exclusion Criteria:

* Pregnant or planning to become pregnant during the conduct of the study
* have a poorly controlled medical condition
* Were involved in a study of an experimental agent within 3 months of enrollment
* Are taking beta-blockers or anabolic agent or potassium wasting diuretics
* have any condition or contraindication which would interfere with testing or preclude use of beta-agonist
* Are taking blood thinners or medications which make a needle muscle biopsy contra-indicated
* Are taking any medications or therapies with a contraindication to Clenbuterol

Primary outcomes:
measure: Frequency of Clenbuterol-related adverse reactions
timeFrame: from baseline to 6 month visit
measure: change in heart rate
timeFrame: from Month 1 to Month 6 visit
measure: change in blood pressure
timeFrame: from Month 1 to Month 6 visit
measure: Safety Lab Potassium (K)
timeFrame: Baseline to month 6 visit
measure: Safety Lab Glucose
timeFrame: Baseline to month 6 visit
measure: Tolerability of 3 doses of clenbuterol in sequential cohorts
timeFrame: from baseline to 6 month visit
measure: Safety ECG
timeFrame: from Month 1 to Month 6 visit
measure: Safety Lab Creatine kinase (CK)
timeFrame: Baseline to Month 6 visit
Secondary outcomes:
measure: MRI
timeFrame: Screening to Month 6 Visit
measure: Muscle Biopsy for RNA sequencing
timeFrame: Baseline and Month 6
measure: FSHD-COM
timeFrame: Screening to Month 6 Visit
measure: Manual Muscle Testing (MMT)
timeFrame: Screening to Month 6 Visit
measure: Quantitative Muscle Testing (QMT)
timeFrame: Screening to Month 6 Visit
measure: Patient Reported Outcome Measurement Information System-57 (Promis57)
timeFrame: Screening to Month 6 Visit
measure: FSHD Rasch-built overall disability scale (FSHD-RODS)
timeFrame: Screening to Month 6 Visit
measure: Upper Extremity Functional Index (UEFI)
timeFrame: Screening to Month 6 visit
measure: Clinical Global Impression of Severity and Change (CGI-S and CGI-C)
timeFrame: Screening to Month 6 visit
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References: