STRIDES - a Clinical Research Study of an Investigational New Drug to Treat Spinocerebellar Ataxia

Study Overview
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Brief Summary
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Phase 2b/3 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).

Detailed Description
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This is a randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of SLS-005 for the treatment of adults with SCA. The study consists of a 2-week screening period, a 52-week treatment period, and a 2-week safety follow-up period. Eligible participants between the ages of 18-75 years, will be randomized to treatment with SLS-005 or equivalent placebo (sodium chloride injection, 0.9%, USP). The study plans to enroll up to 245 participants with SCA3. Biomarkers associated with neuro-axonal injury, pharmacokinetics, Modified Scale for Assessment and Rating of Ataxia (m-SARA), 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), will be assessed at screening and/or baseline and at scheduled times throughout the study.

Official Title
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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

Conditions
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Spinocerebellar Ataxia Type 3

Intervention / Treatment
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* Drug: SLS-005
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Men and women, 18 to 75 years (inclusive) of age. Clinical diagnosis of SCA3 with documented genetic confirmation. m-SARA total score ≥ 4 at the screening visit. m-SARA gait component score ≥ 1 at the screening visit. Body Mass Index (BMI) between 18 kg/m2 and 35 kg/m2 (inclusive). Stable doses of all concomitant medications for at least 30 days prior to the screening visit. Negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy result at the screening visit for female participants of childbearing potential. Willingness to comply with sexual abstinence or contraception guidelines of this study. Exclusion Criteria: Any hereditary ataxia that is not genetically confirmed to be SCA type 3, or any type of ataxia that is acquired or secondary to another medical condition including but not limited to, alcoholism, head injury, multiple sclerosis, olivopontocerebellar atrophy, multiple system atrophy, or stroke. A score of 4 on any 1 of the 4 items that comprise the m-SARA. Current participation in another clinical trial or completed participation in an interventional trial less than 30 days prior to the screening visit (90 days for a biological treatment). Current diagnosis and/or healthcare professional-recommended treatment (medication and/or diet) of diabetes mellitus type 1 or type 2. Hemoglobin A1c (HbA1c) ≥ 6.5% at the screening visit Prior treatment with SLS-005, any other IV trehalose formulation, or known hypersensitivity to trehalose. Pregnant or breastfeeding. History of alcohol or drug abuse within the last 2 years. Chronic liver disease including Hepatitis B; Hepatitis C unless successful curative treatment is documented; human immunodeficiency virus (HIV) infection. Prior history of drug-induced liver injury (DILI) and/or laboratory results at screening that indicate inadequate liver function (e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT] > 2 times the upper limit of normal [x ULN] and/or total bilirubin level > 2 x ULN). Laboratory results at screening that indicate inadequate renal function (e.g., estimated creatinine clearance of < 60 mL/min calculated by the Cockcroft and Gault formula). Any current cardiovascular disease or abnormality on 12-lead ECG at screening that, in the investigator's opinion, is clinically significant and could be a potential safety risk to the participant. Any current psychiatric, neurological, or cognitive disorder that, in the investigator's opinion, may interfere with the participant's ability to provide informed consent or appropriately complete the study's safety or efficacy assessments. Significant suicide risk as indicated by a yes response to question #4 or #5 under Suicidal Ideation in the past 6 months or any yes response under Suicidal Behavior in the past 3 years on the Columbia Suicide Severity Rating Scale (C-SSRS) during the screening visit. Any other medical condition or abnormal finding during screening that, in the investigator's opinion, could confound collection or interpretation of safety or efficacy data or be a potential safety risk to the participant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLS-005 0.75 g/kg Dose<br>SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion). SLS-005 will be administered as a weight-based dose of 0.75 g/kg by IV infusion once a week. For 52 weeks | Drug: SLS-005<br>* SLS-005<br>|
| Experimental: SLS-005 0.50 g/kg Dose<br>SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion). SLS-005 will be administered as a weight-based dose of 0.50 g/kg by IV infusion once a week. For 52 weeks | Drug: SLS-005<br>* SLS-005<br>|
| Placebo Comparator: Placebo volume equivalent to a SLS-005 0.75 g/kg dose calculation<br>Placebo (sodium chloride injection, 0.9, USP) will be administered by IV infusion once a week as a weight-based volume equivalent to a SLS-005 0.75 g/kg dose. For 52 weeks | Drug: Placebo<br>* Placebo (sodium chloride injection, 0.9%, USP)<br>|
| Placebo Comparator: Placebo volume equivalent to a SLS-005 0.50 g/kg dose calculation<br>Placebo (sodium chloride injection, 0.9, USP) will be administered by IV infusion once a week as a weight-based volume equivalent to a SLS-005 0.50 g/kg dose. For 52 weeks | Drug: Placebo<br>* Placebo (sodium chloride injection, 0.9%, USP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy: m-SARA | Mean change from baseline in Modified Scale for Assessment and Rating of Ataxia (m-SARA) total score at week 52 | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: CGI-S | Mean change from baseline in Clinical Global Impression of Severity (CGI-S) score at week 52 | 4, 13, 26, 39, and 52 weeks | 
| Efficacy: PGI-S | Mean change from baseline in Patient Global Impression of Severity (PGI-S) score at week 52 | 4, 13, 26, 39, and 52 weeks | 
| Efficacy: FARS-ADL | Mean change from baseline in Friedreich's Ataxia Rating Scale (FARS) for the assessment of performance in basic activities that are typically required daily for independent living. | 4, 13, 26, 39, and 52 weeks | 
| Efficacy: m-SARA | Mean change from baseline in m-SARA total score at week 26. | 26 weeks | 
| Efficacy: m-SARA | Mean change from baseline in m-SARA total score at weeks 4, 13, 26, 39, and 52 | 52 weeks | 
| Safety: Adverse Events | Incidences of Treatment-Emergent Adverse Events and Serious Adverse Events (SAEs), including clinically significant laboratory and electrocardiogram (ECG) abnormalities. | 56 weeks |