Evaluation of the Safety and Efficacy of AMX0035 (Phenylbutyrate, Ursodoxicoltaurine) in Adult Patients with Amyotrophic Lateral Sclerosis

The primary objective of this study is to evaluate the impact of **AMX0035** treatment compared to placebo on disease progression over 48 weeks in adult patients with **Amyotrophic Lateral Sclerosis (ALS)**. This objective is clinically relevant as it aims to determine the efficacy of AMX0035 in slowing the progression of ALS, a neurodegenerative disease characterized by the progressive loss of motor neurons, which can lead to significant disability and reduced life expectancy.

Secondary objectives include:

• Assessing patient quality of life during treatment with AMX0035 compared to placebo.
• Evaluating the impact of AMX0035 on overall survival compared to placebo.
• Assessing the impact of AMX0035 on Slow Vital Capacity (SVC) compared to placebo.
• Evaluating the impact of AMX0035 treatment compared to placebo on disease progression over 24 weeks in adult patients with ALS.

These secondary objectives are important for understanding the broader effects of AMX0035 on patient outcomes, including quality of life, respiratory function, and survival, which are critical factors in the management of ALS.

The clinical trial involves a total of **138 participants** diagnosed with **Amyotrophic Lateral Sclerosis (ALS)**. The study population includes both male and female adults, aged 18 years and older, who have been diagnosed with ALS either as clinically definite or clinically probable according to the World Federation of Neurology revised El Escorial criteria. Participants were selected based on their ability to provide informed consent and their capability and willingness to adhere to trial procedures, including clinic visits and status reporting. The trial population is characterized by a stable health regimen if treated with riluzole and/or edaravone, ensuring that these treatments were initiated and maintained at a stable regimen prior to the baseline visit. Lifestyle considerations include the requirement for women of childbearing potential to use adequate birth control and for men to practice contraception throughout the trial and for three months after the last dose of the study drug. The trial does not include pregnant women or those planning to become pregnant during the study period. The selection criteria ensure a focus on individuals who can comply with the trial's demands and who are not planning significant lifestyle changes that could affect the study's outcomes.

The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of AMX0035 in adult patients with **Amyotrophic Lateral Sclerosis (ALS)**. The trial aims to assess the impact of AMX0035 treatment compared to placebo on disease progression over a 48-week period. Participants will be randomly assigned to receive either the investigational product, AMX0035, or a placebo, with both administered in powder form for oral use. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, diagnosis, and treatment history.

Following the screening, eligible participants will undergo a baseline visit where initial assessments and measurements will be conducted. Subsequent follow-up visits will occur at regular intervals to monitor the participants' health status, adherence to the trial protocol, and any changes in the primary and secondary endpoints. The primary endpoint is the change from baseline in the ALSFRS-R total score at Week 48, adjusted for mortality. Secondary endpoints include changes in ALSAQ-40 Total Score, overall survival, and percent predicted SVC, among others.

The trial is expected to last until January 2026, with participant involvement spanning approximately 48 weeks. Conditions that may lead to early termination from the study include non-compliance with trial procedures, adverse events, or withdrawal of consent. Participants are required to adhere to specific contraceptive measures during the trial and for three months after the last dose of the study drug. The trial is not categorized as low intervention and is intended to provide therapeutic confirmatory data for the treatment of ALS.

The clinical trial involves the administration of **AMX0035**, an experimental medication formulated as a **powder**. The active substances in AMX0035 are **phenylbutyrate** and **ursodoxicoltaurine**, both of which are of chemical origin. The medication is administered orally, with a maximum daily dose of 2 units and a total maximum dose of 686 units over a treatment period of 50 weeks. The pharmaceutical form of AMX0035 is designed for oral use, and it is not a pediatric formulation. The trial aims to evaluate the safety and efficacy of AMX0035 in adult patients with Amyotrophic Lateral Sclerosis (ALS) over a 48-week period.

The study also includes a **placebo** treatment, referred to as PL1 Oral powder in sachet, oral use. This placebo is used as a comparator to assess the impact of AMX0035 on disease progression. The placebo is administered in a similar manner to the experimental medication, ensuring that the trial remains double-blind and placebo-controlled. The placebo does not contain any active substances and serves to provide a baseline for evaluating the effects of the experimental treatment.

The efficacy of AMX0035 in the treatment of **Amyotrophic Lateral Sclerosis (ALS)** will be assessed through a series of primary and secondary endpoints over a 48-week period. The primary endpoint is the change from baseline in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score at Week 48, adjusted for mortality. This scale is a validated tool used to measure the functional status of patients with ALS, providing a comprehensive assessment of disease progression.

Secondary endpoints include the change from baseline in the ALS Assessment Questionnaire-40 (ALSAQ-40) Total Score at Week 48, which evaluates the quality of life in ALS patients. Additionally, overall survival will be monitored, along with the change from baseline to Week 48 in the percent predicted Slow Vital Capacity (SVC) using in-clinic visits. Another secondary endpoint is the change from baseline in the ALSFRS-R total score at Week 24, offering an interim analysis of functional status.

Data collection will occur at specified timepoints, including baseline, Week 24, and Week 48, to ensure a comprehensive evaluation of the treatment's impact. The use of validated scales and in-clinic assessments will facilitate accurate and reliable measurement of efficacy parameters. The analysis will focus on comparing the outcomes between the AMX0035 treatment group and the placebo group to determine the treatment's effectiveness in slowing disease progression and improving patient outcomes.