Phase 2 Randomized, Double-blind, Placebo-controlled Study of Emrusolmin in Adult Patients with Multiple System Atrophy

The primary objective of this study is to evaluate the **efficacy** of TEV-56286, administered orally, for the treatment of adult patients with **Multiple System Atrophy** (MSA). This is clinically relevant as MSA is a progressive neurodegenerative disorder with limited treatment options, and assessing the efficacy of TEV-56286 could potentially lead to improved therapeutic strategies for managing this condition.

Secondary objectives include:

• Evaluating specific efficacy parameters of TEV-56286 beyond the measure of the primary objective.
• Assessing the safety and tolerability of TEV-56286.

The clinical trial involves a total of **97 participants** diagnosed with **Multiple System Atrophy** (MSA). The study population includes both male and female subjects aged 30 years and older. Participants were selected based on their classification as "clinically possible" or "clinically probable" MSA according to the Gilman criteria. Additionally, participants must be able to ambulate at least 10 meters without assistance, although the use of a cane is permitted. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of participants. The sponsor has not provided further details regarding the general health status or specific lifestyle habits of the participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of TEV-56286, also known as Emrusolmin, in adult patients diagnosed with **Multiple System Atrophy** (MSA). The trial will be conducted over a period of 56 weeks, with the primary objective being the assessment of the efficacy of TEV-56286 administered orally. Participants will be randomly assigned to receive either the active treatment or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.

The trial will commence with an inclusion (screening) visit, where potential participants will be evaluated against the principal inclusion criteria, which include being 30 years or older, having a diagnosis of "clinically possible" or "clinically probable" MSA according to the Gilman criteria, and the ability to ambulate at least 10 meters without assistance. Following successful screening, eligible participants will be enrolled in the study and will undergo baseline assessments.

Throughout the trial, participants will attend regular follow-up visits to monitor their health status and the effects of the treatment. These visits will include assessments of the primary efficacy endpoint, which is the change from baseline to week 48 in the modified Unified Multiple System Atrophy Rating Scale (UMSARS) part I score, excluding item 11. Secondary endpoints will also be evaluated, including the total UMSARS score, Clinical Global Impression-Severity (CGI-S), and MSA Quality of Life (MSA-QoL) scores. Safety endpoints will be assessed by monitoring adverse events, vital signs, laboratory test values, and ECG measurements.

The expected length of participant involvement is approximately 56 weeks, with the study estimated to conclude by June 2027. Conditions that may lead to early termination from the study include the occurrence of adverse events that necessitate withdrawal, as well as any significant deviations from the study protocol. The end-of-study visit will involve final assessments to evaluate the overall impact of the treatment and to ensure participant safety upon completion of the trial.

The clinical trial involves the administration of **Emrusolmin**, an investigational medicinal product, for the treatment of patients with Multiple System Atrophy (MSA). Emrusolmin is provided in a **capsule** form and is intended for **oral use**. The maximum daily dose of Emrusolmin is 300 mg, with a total maximum dose of 100.8 g over the course of the study. The treatment period is set for a maximum of 48 weeks. Emrusolmin is a chemical entity developed by TEVA Branded Pharmaceutical Products R&D, Inc., and is identified by the sponsor product code TEV-56286. The active substance in Emrusolmin is of chemical origin, and the product is not formulated for pediatric use.

The study also includes a **placebo** to match the investigational medicinal product TEV-56286. The placebo is used as a comparator treatment in this double-blind, randomized, placebo-controlled, parallel-group Phase 2 study. The placebo is designed to mimic the appearance and administration route of Emrusolmin, ensuring blinding is maintained throughout the trial. The placebo does not contain any active substance and is administered in the same manner as the investigational product, following the same dosing schedule and frequency.

The efficacy of TEV-56286 in the treatment of adult patients with **Multiple System Atrophy (MSA)** will be assessed through a multi-centered, double-blind, randomized, placebo-controlled, parallel group Phase 2 study. The primary efficacy endpoint is the change from baseline to week 48 in the modified Unified Multiple System Atrophy Rating Scale (UMSARS) part I, excluding item 11, with item scoring rescaled from 0 to 3. Secondary efficacy endpoints include the total UMSARS score (part I and part II combined), UMSARS part I score, Clinical Global Impression-Severity (CGI-S), and Multiple System Atrophy Quality of Life (MSA-QoL).

These efficacy parameters will be measured and collected at baseline and at week 48. The analysis will compare the changes in these scores between the TEV-56286 and placebo groups. The study will utilize validated scales such as UMSARS, CGI-S, and MSA-QoL to ensure the reliability and accuracy of the efficacy assessments. The trial is designed to provide comprehensive data on the efficacy of TEV-56286 over a 48-week treatment period.