Clenbuterol to Target DUX4 in FSHD (Target FSHD)

Jeffrey Statland

Status and phase: Not yet enrolling; Phase 1

Conditions: Muscular Dystrophy, Facioscapulohumeral

Treatments: Drug: Clenbuterol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06721299

P50AR065139 (U.S. NIH Grant/Contract)

STUDY00150777

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

30 participants in 3 patient groups

Clenbuterol Cohort 1

Experimental group

Description:

20 mcg taken orally twice daily

Treatment:

Drug: Clenbuterol

Clenbuterol Cohort 2

Experimental group

Description:

40 mcg taken orally twice daily

Treatment:

Drug: Clenbuterol

Clenbuterol Cohort 3

Experimental group

Description:

60 mcg taken orally twice daily

Treatment:

Drug: Clenbuterol