A Phase 1/2a, Randomized, Double Blind, Placebo Controlled, Single and Multiple Dose Escalation Study in Healthy Volunteers and an Expansion Cohort in Adult Participants With Amyotrophic Lateral Sclerosis (ALS) to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SPG302
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 88
- 试验地点
- 4
- 主要终点
- Safety and tolerability in healthy volunteers (SAD cohort)
研究概览
简要总结
The first-in-human Phase 1 study described herein will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SPG302 in healthy volunteers and ALS participants
详细描述
This study is a Phase 1 randomized, double-blind, placebo-controlled, single, and multiple ascending dose study in HV with food effect cohort, and a repeat dose expansion cohort(s) in participants with ALS.
The study consists of 3 parts, as follows:
- Part 1: SAD in HV with up to 6 cohorts including a food effect cohort.
- Part 2: MAD over 5 days in HV with up to 5 cohorts
- Part 3: ALS cohorts with once daily (QD) dosing over 28 day cycles
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blinded
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-55
- •Must be in good health with no significant medical history
- •Clinical laboratory values within normal range or < 1.2 times ULN
- •BMI 18-32 (inclusive)
- •Contraceptive use by men or women consistent with local regulations
- •Able and willing to provide written informed consent
排除标准
- •Any physical or psychological condition that prohibits study completion
- •Known cardiac disease
- •Active or history of malignancy in the past 5 years
- •Serious infection within 1 month of screening
- •Acute illness within 30 days of Day 1
- •Surgery, bone fracture, or major musculoskeletal injury in the past 3 months
- •History of suicidal behavior or suicidal ideation
- •Active cigarette smokers and users of nicotine-containing products
- •HIV, hepatitis B and hepatitis C positive
- •SBP >140 or <90
- •DBP >90 or <40
- •HR <40 or >100
- •QTcF >450ms, cardiac arrhythmia, or clinically significant abnormal ECG
- •Prescriptions, over-the-counter, or herbal medication within 7 days
- •Vaccines within 14 days
- •Other investigational products within 30 days
- •Blood donation within 30 days
- •Plasma donation within 7 days
- •Pregnant or breastfeeding
- •Otherwise unfit, on metabolic-altering lifestyle/diet, positive urine drug screen or intake of alcohol or caffeine-containing products
- •ALS Cohort Inclusion Criteria:
- •Age 18-80
- •ALS TRICALS risk score
- •Stable dose of standard of care treatment
- •Contraception use by men or women consistent with local regulations
- •Able and willing to provide written informed consent
- •ALS Cohort Exclusion Criteria:
- •Underlying physical or psychological condition prohibiting study completion
- •Known cardiac disease
- •Active or history of malignancy in the past 5 years
- •Serious infection within 1 month of screening
- •Acute illness within 30 days of Day 1
- •History of suicidal behavior or suicidal ideation
- •Active cigarette smokers and users of nicotine-containing products
- •Neurodegenerative disease
- •External respiratory support or supplemental oxygen requirement
- •HIV, hepatitis B and hepatitis C positive
- •SBP >140 or <90
- •DBP >90 or <40
- •HR <40 or >100
- •QTcF >450ms, cardiac arrhythmia, or clinically significant abnormal ECG
- •Vaccines within 14 days
- •Other investigational products within 30 days
- •Blood donation within 30 days
- •Plasma donation within 7 days
- •Pregnant or breastfeeding
- •Otherwise unfit
研究组 & 干预措施
Experimental Part 1: Active SPG302 to be administered to healthy volunteers (SAD)
8 participants will be randomized in a 3:1 ratio to active or placebo. Study intervention will be administered orally once. Randomization to each SAD cohort will be done in a staggered manner; initially 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed and after a safety evaluation period after the dose without clinically significant adverse events (AEs) and investigator approval, then, 6 additional participants will be randomized and dosed (5 active and 1 placebo) at the discretion of the Investigator according to the randomization schedule
干预措施: SPG302 (Drug)
Placebo Comparator Part 1: Placebo comparator to be administered to healthy volunteers (SAD)
8 participants will be randomized in a 3:1 ratio to active or placebo. Study intervention will be administered orally once. Randomization to each SAD cohort will be done in a staggered manner; initially 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed and after a safety evaluation period after the dose without clinically significant adverse events (AEs) and investigator approval, then, 6 additional participants will be randomized and dosed (5 active and 1 placebo) at the discretion of the Investigator according to the randomization schedule
干预措施: Placebo (Drug)
Experimental Part 2: Active SPG302 to be administered to healthy volunteers (MAD)
8 participants will be randomized in a 3:1 ratio to active or placebo. Participants will receive study intervention QD over 5 days and will be discharged on Day 6. A follow-up safety visit will be conducted on Day 12 (±3 days).
干预措施: SPG302 (Drug)
Placebo Comparator Part 2: Placebo comparator to be administered to healthy volunteers (MAD)
8 participants will be randomized in a 3:1 ratio to active or placebo. Participants will receive study intervention QD over 5 days and will be discharged on Day 6. A follow-up safety visit will be conducted on Day 12 (±3 days).
干预措施: Placebo (Drug)
Experimental Part 3: Active SPG302 to be administered to participants with ALS
Participants with ALS will be randomized to receive SPG302 or placebo at a 3:1 ratio. Study intervention will be administered QD over 28 days. A follow-up safety visit will be conducted 30 days after last dose (±7 days). Participants who complete Part 3 may be offered to participate in an open-label extension.
干预措施: SPG302 (Drug)
Placebo Comparator Part 3: Placebo comparator to be administered to participants with ALS
Participants with ALS will be randomized to receive SPG302 or placebo at a 3:1 ratio. Study intervention will be administered QD over 28 days. A follow-up safety visit will be conducted 30 days after last dose (±7 days). Participants who complete Part 3 may be offered to participate in an open-label extension.
干预措施: Placebo (Drug)
Experimental Part 3: Open Label Extension - Active SPG302 administered to participants with ALS
Participants with ALS will be randomized to receive SPG302 or placebo at a 3:1 ratio. Study intervention will be administered QD over 28 days for up to 3 cycles in the USA and up to 12 cycles in Australia. A follow-up safety visit will be conducted 30 days after last dose (±7 days).
干预措施: SPG302 (Drug)
结局指标
主要结局
Safety and tolerability in healthy volunteers (SAD cohort)
时间窗: 7 days
• Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Safety and tolerability in healthy volunteers (SAD food effect cohort)
时间窗: 15 days
• Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Safety and tolerability in participants with ALS
时间窗: 60 days
• Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Safety and tolerability in healthy volunteers (MAD cohort)
时间窗: 12 days
• Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
次要结局
- Clinical efficacy measures of SPG302 in participants with ALS(12 mon)
- Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD cohort)(7 days)
- Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD food effect cohort)(15 days)
- Plasma pharmacokinetics of SPG302 in healthy volunteers (MAD cohort)(12 days)
- Plasma pharmacokinetics of SPG302 in participants with ALS(12mon)
- Clinical outcomes of multiple oral doses of SPG302 in participants with ALS(12 mon)