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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 23
- 主要终点
- Primary Efficacy: m-SARA
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
SLS-005 0.75 g/kg Dose
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
干预措施: SLS-005 (Drug)
SLS-005 0.50 g/kg Dose
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
干预措施: SLS-005 (Drug)
Placebo volume equivalent to a SLS-005 0.75 g/kg dose calculation
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
干预措施: Placebo (Drug)
Placebo volume equivalent to a SLS-005 0.50 g/kg dose calculation
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
干预措施: Placebo (Drug)
结局指标
主要结局
Primary Efficacy: m-SARA
时间窗: 52 weeks
Mean change from baseline in Modified Scale for Assessment and Rating of Ataxia (m-SARA) total score at week 52
次要结局
- Efficacy: FARS-ADL(4, 13, 26, 39, and 52 weeks)
- Efficacy: m-SARA(52 weeks)
- Efficacy: CGI-S(4, 13, 26, 39, and 52 weeks)
- Efficacy: PGI-S(4, 13, 26, 39, and 52 weeks)
- Safety: Adverse Events(56 weeks)