A DOUBLE-BLIND, RANDOMIZED, PLACEBO CONTROLLED TRIAL TO ASSESS SAFETY AND EFFICACY OF SLS-005 (TREHALOSE INJECTION, 90.5 MG/ML FOR INTRAVENOUS INFUSION) FOR THE TREATMENT OF ADULTS WITH SPINOCEREBELLAR ATAXIA

The primary objective of this clinical trial is to determine the **efficacy** of SLS-005 (Trehalose Injection) at a dosage of 0.75 g/kg for the treatment of **Spinocerebellar Ataxia type-3 (SCA3)** in adults. This objective is clinically relevant as it aims to assess the potential therapeutic benefits of SLS-005 in improving the condition of patients suffering from SCA3, a progressive neurodegenerative disorder characterized by motor incoordination and other neurological symptoms.

Secondary objectives include:

• Determining the **safety** and **tolerability** of SLS-005 for the treatment of SCA3 in adults. This is crucial for evaluating the risk-benefit profile of the investigational drug, ensuring that it is not only effective but also safe for patient use.

The clinical trial investigating the efficacy of SLS-005 0.75 g/kg for the treatment of **Spinocerebellar Ataxia type-3 (SCA3)** involves a total of 187 participants. The study population comprises both male and female adults aged between 18 and 75 years, inclusive. Participants were selected based on a clinical diagnosis of SCA3 with documented genetic confirmation. The general health status of the participants includes a Body Mass Index (BMI) ranging from 18 kg/m² to 35 kg/m². All participants are required to have stable doses of concomitant medications for at least 30 days prior to the screening visit. Lifestyle considerations include adherence to sexual abstinence or contraception guidelines as part of the study requirements. The trial includes a vulnerable population, and participants must have a modified Scale for the Assessment and Rating of Ataxia (m-SARA) total score of 4 or higher, with a gait component score of at least 1 at the screening visit. Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy result at the screening visit.

The clinical trial is designed as a **double-blind**, randomized, placebo-controlled study to evaluate the safety and efficacy of SLS-005, a **solution for infusion** containing **trehalose dihydrate**, for the treatment of adults with Spinocerebellar Ataxia type-3 (SCA3). The trial aims to determine the efficacy of SLS-005 at a dosage of 0.75 g/kg over a period of 52 weeks. Participants will be randomly assigned to receive either the investigational drug or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the study's **double-blind** nature.

The trial will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as age between 18 and 75 years, a clinical diagnosis of SCA3 with genetic confirmation, and a stable medication regimen. The primary endpoint is the change from baseline in the modified Scale for the Assessment and Rating of Ataxia (m-SARA) total score at Week 52. Secondary endpoints include changes in Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Severity (PGI-S), and Friedreich’s Ataxia Rating Scale – Activities of Daily Living (FARS-ADL) scores at various time points throughout the study.

Participants will attend regular follow-up visits at Weeks 4, 13, 26, 39, and 52 to assess the treatment's impact and monitor for any treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs). The end-of-study visit will occur at Week 52, marking the conclusion of the participant's involvement in the trial. The expected duration of participant involvement is approximately 52 weeks, with conditions for early termination including significant protocol deviations, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation of the study drug.

The clinical trial involves the administration of **SLS-005**, a pharmaceutical formulation containing **trehalose dihydrate (Ph.Eur.)** as the active substance. This investigational product is provided as a **solution for infusion** and is intended for **intravenous infusion**. The dosage regimen for SLS-005 is set at 0.75 g/kg, with a maximum daily dose of 750 mg/kg and a total maximum dose of 39,000 mg/kg over the course of the treatment period. The treatment duration is specified to last up to 52 weeks. The investigational product is not formulated for pediatric use and is classified as an orphan drug, with the designation number EU/3/15/1502. The product is developed by Seelos Therapeutics Inc.

The trial also includes a **placebo** control, which is a **solution for infusion** composed of **sodium chloride 0.9%**. This placebo is designed to match the investigational product in appearance and administration route, ensuring the double-blind nature of the study. The placebo serves as a comparator to assess the efficacy and safety of SLS-005 in the treatment of adults with **spinocerebellar ataxia**. The administration schedule for the placebo mirrors that of the investigational product, maintaining consistency in dosing frequency and duration.

The efficacy of SLS-005 (trehalose injection) for the treatment of adults with **spinocerebellar ataxia type-3 (SCA3)** will be assessed through a double-blind, randomized, placebo-controlled trial. The primary endpoint for evaluating efficacy is the change from baseline in the modified Scale for the Assessment and Rating of Ataxia (m-SARA) total score at Week 52 in participants treated with SLS-005 0.75 g/kg compared to placebo. Secondary endpoints include changes from baseline in the Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Severity (PGI-S), and Friedreich’s Ataxia Rating Scale – Activities of Daily Living (FARS-ADL) scores at Week 52. Additionally, changes from baseline in m-SARA total score will be assessed at Week 26, and further changes in m-SARA, CGI-S, PGI-S, and FARS-ADL scores will be evaluated at Weeks 4, 13, 26, and 39. The trial will also monitor incidences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant laboratory and ECG abnormalities.