Clenbuterol to Target DUX4 in FSHD

Официальное название

Clenbuterol to Target DUX4 in FSHD (Target FSHD): Open Label Safety and Tolerability Study of 3 Doses of Clenbuterol

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Clenbuterol
  Beta-Agonist

Первичные конечные точки

• Frequency of Clenbuterol-related adverse reactions [Срок оценки: from baseline to 6 month visit]
• change in heart rate [Срок оценки: from Month 1 to Month 6 visit]
• change in blood pressure [Срок оценки: from Month 1 to Month 6 visit]
• Safety Lab Potassium (K) [Срок оценки: Baseline to month 6 visit]
• Safety Lab Glucose [Срок оценки: Baseline to month 6 visit]
• Tolerability of 3 doses of clenbuterol in sequential cohorts [Срок оценки: from baseline to 6 month visit]
• Safety ECG [Срок оценки: from Month 1 to Month 6 visit]
• Safety Lab Creatine kinase (CK) [Срок оценки: Baseline to Month 6 visit]

Вторичные конечные точки (9)

• MRI [Срок оценки: Screening to Month 6 Visit]
• Muscle Biopsy for RNA sequencing [Срок оценки: Baseline and Month 6]
• FSHD-COM [Срок оценки: Screening to Month 6 Visit]
• Manual Muscle Testing (MMT) [Срок оценки: Screening to Month 6 Visit]
• Quantitative Muscle Testing (QMT) [Срок оценки: Screening to Month 6 Visit]
• Patient Reported Outcome Measurement Information System-57 (Promis57) [Срок оценки: Screening to Month 6 Visit]
• FSHD Rasch-built overall disability scale (FSHD-RODS) [Срок оценки: Screening to Month 6 Visit]
• Upper Extremity Functional Index (UEFI) [Срок оценки: Screening to Month 6 visit]
• Clinical Global Impression of Severity and Change (CGI-S and CGI-C) [Срок оценки: Screening to Month 6 visit]

Критерии участия

Критерии включения

• 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 0 and 10
• 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
• agree to follow the contraceptive requirement for duration of the study

Критерии исключения

• 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
• Are taking or are planning to take a GLP-1 Agonist during trial
• 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
• Has contraindication to lactose such as galactosmia, lactase deficiency and glucose-galactose malabsorption. For those who are lactose intolerant, the PI will determine acceptability based on tolerance reaction to lactose
• Are taking any medications or therapies with a contraindication to Clenbuterol

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• University of Kansas Medical Center — Kansas City
• University of Rochester Medical Center — Rochester
• University of Washington — Seattle

Идентификаторы

NCT: NCT06721299 · STUDY00150777 · P50AR065139

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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