Study of SPG302 in Healthy Volunteers and ALS Participants
Phase 1
Active, not recruiting
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT05882695
- Lead Sponsor
- Spinogenix
- Brief Summary
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
- Detailed Description
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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 112
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo Comparator Part 3: Placebo comparator to be administered to participants with ALS Placebo 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. Placebo Comparator Part 1: Placebo comparator to be administered to healthy volunteers (SAD) Placebo 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 Placebo Comparator Part 2: Placebo comparator to be administered to healthy volunteers (MAD) Placebo 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). Experimental Part 2: Active SPG302 to be administered to healthy volunteers (MAD) SPG302 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). Experimental Part 3: Active SPG302 to be administered to participants with ALS SPG302 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. Experimental Part 1: Active SPG302 to be administered to healthy volunteers (SAD) SPG302 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 Experimental Part 3: Open Label Extension - Active SPG302 administered to participants with ALS SPG302 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).
- Primary Outcome Measures
Name Time Method Safety and tolerability in healthy volunteers (SAD cohort) 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) 15 days • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Safety and tolerability in participants with ALS 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) 12 days • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
- Secondary Outcome Measures
Name Time Method Clinical efficacy measures of SPG302 in participants with ALS 12 mon The Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R).
Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD cohort) 7 days PK parameters of SPG302 on concentrations in plasma
Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD food effect cohort) 15 days Effects of food on SPG302 PK profile
Plasma pharmacokinetics of SPG302 in healthy volunteers (MAD cohort) 12 days PK parameters of SPG302 on concentrations in plasma
Plasma pharmacokinetics of SPG302 in participants with ALS 12mon PK parameters of SPG302 on concentrations in plasma
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS 12 mon Spirometry
Trial Locations
- Locations (4)
Macquarie University
🇦🇺North Ryde, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Flinders Medical center
🇦🇺Adelaide, South Australia, Australia
Nucleus Melbourne (healthy volunteers)
🇦🇺Melbourne, Victoria, Australia