Efficacy and Safety Evaluation of Clenbuterol Hydrochloride in Spinal and Bulbar Muscular Atrophy: A Placebo-Controlled Clinical Trial

The primary objective of this study is to assess the **efficacy** of chronic treatment with clenbuterol in patients with **Spinal and Bulbar Muscular Atrophy (SBMA)**. This is clinically relevant as SBMA is a progressive neuromuscular disorder, and effective treatment options are limited. Evaluating the efficacy of clenbuterol could potentially lead to improved management and therapeutic strategies for individuals affected by this condition.

Secondary objectives include:

• The assessment of the persistence of the effect (if any) after prolonged treatment.
• The assessment of the tolerability of the assigned treatment in terms of treatment-emergent adverse effects.

The clinical trial focuses on **Spinal and Bulbar Muscular Atrophy** (SBMA) and involves a study population exclusively composed of male participants. The age range for eligible participants is between 18 and 75 years, inclusive of 364 additional days. Participants must have a genetically confirmed diagnosis of SBMA, characterized by an androgen receptor CAG repeat number of 38 or greater. The trial population was selected based on the presence of one or more clinical symptoms, such as muscle atrophy, limb weakness, or bulbar palsy, and the ability to walk independently, with or without a cane or other supporting device, excluding wheelchairs. All participants are required to provide written informed consent. The sponsor has not provided information regarding the total number of participants. The study does not include female subjects or vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are mentioned.

The clinical trial is designed to evaluate the **efficacy** and safety of **clenbuterol hydrochloride** in patients diagnosed with **Spinal and Bulbar Muscular Atrophy (SBMA)**. This study is a randomized, double-blind, placebo-controlled trial, conducted over a period of 48 weeks. Participants will be randomly assigned to receive either the active treatment, Monores® 20 microgrammi Compresse, or a placebo. The trial will include a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a genetically confirmed diagnosis of SBMA and the ability to walk independently.

Following the screening, participants will undergo a baseline visit where initial assessments will be conducted. Subsequent follow-up visits will occur at regular intervals throughout the 48-week treatment period, during which primary and secondary endpoints will be evaluated. The primary endpoint is defined as a 15% increase in the distance covered in six minutes at the 6-Minute Walk Test (6MWT) at week 48 compared to baseline. Secondary endpoints include assessments of SBMA-FRS, AMAT, FVC, 6K total score, serum creatinine levels, ALSAQ-40, and INQOL scores.

The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the overall efficacy and safety of the treatment. Participants are expected to be involved in the study for the entire 48-week duration unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent. The trial is scheduled to commence recruitment in April 2024, with an estimated completion date by the end of December 2026.

The clinical trial involves the administration of **Monores® 20 microgrammi Compresse**, which contains the active substance **clenbuterol hydrochloride**. This experimental medication is provided in the form of a **tablet** and is administered **orally**. The dosage is set at **20 micrograms** per tablet, with a maximum daily dose of **40 micrograms**. The treatment period is capped at **48 weeks**. The medication is manufactured by VALEAS S.P.A. and is classified under the ATC code **R03CC13**, indicating its use as a bronchodilator. The chemical origin of the active substance is noted, and the trial aims to evaluate the efficacy and safety of clenbuterol in patients with Spinal and Bulbar Muscular Atrophy (SBMA).

In addition to the experimental medication, a **placebo** is utilized as a comparator treatment in this study. The placebo is designed to mimic the appearance of the Monores® tablet but contains no active pharmaceutical ingredients. The placebo serves as a control to assess the true efficacy of the clenbuterol treatment by providing a baseline for comparison. The administration route and frequency for the placebo are consistent with those of the experimental medication to ensure blinding and maintain the integrity of the trial results.

The efficacy of clenbuterol in patients with Spinal and Bulbar Muscular Atrophy (SBMA) will be assessed through a placebo-controlled study. The primary endpoint for evaluating efficacy is the percentage of responders in the two treatment arms, defined as subjects achieving a 15% increase in the distance covered in six minutes during the 6-Minute Walk Test (6MWT) at week 48 (V7) compared to baseline. Secondary endpoints include various measures assessed over the 48-week treatment period from V2 to V7. These measures are the 6MWT, SBMA Functional Rating Scale (SBMA-FRS) total score, Adult Myopathy Assessment Tool (AMAT) total score, Forced Vital Capacity (FVC), 6K total score, serum creatinine levels, Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) total score, and Individualized Neuromuscular Quality of Life (INQOL) total score. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to determine the impact of the treatment on the participants.