Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SPG302 in Healthy Volunteers and ALS Participants

Study Overview
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Brief Summary
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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
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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 days

Official Title
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A Phase 1, 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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: SPG302
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 Must be in good health with no significant medical history Clinical laboratory values within normal range 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 FVC>80% ALSFRS-R >=12 points 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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1 randomized, double-blind, placebo-controlled, single, and multiple ascending dose study in HV and a repeat dose expansion in cohort(s)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Part 1: Active SPG302 to be administered to healthy volunteers (SAD)<br>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 | Drug: SPG302<br>* synthetic small molecule<br>|
| Placebo Comparator: Placebo Comparator Part 1: Placebo comparator to be administered to healthy volunteers (SAD)<br>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 | Drug: Placebo<br>* Placebo<br>|
| Experimental: Experimental Part 2: Active SPG302 to be administered to healthy volunteers (MAD)<br>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). | Drug: SPG302<br>* synthetic small molecule<br>|
| Placebo Comparator: Placebo Comparator Part 2: Placebo comparator to be administered to healthy volunteers (MAD)<br>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). | Drug: Placebo<br>* Placebo<br>|
| Experimental: Experimental Part 3: Active SPG302 to be administered to participants with ALS<br>12 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. | Drug: SPG302<br>* synthetic small molecule<br>|
| Placebo Comparator: Placebo Comparator Part 3: Placebo comparator to be administered to participants with ALS<br>12 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. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability in healthy volunteers (SAD cohort) | • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 7 days | 
| Safety and tolerability in healthy volunteers (SAD food effect cohort) | • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 15 days | 
| Safety and tolerability in healthy volunteers (MAD cohort) | • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 12 days | 
| Safety and tolerability in participants with ALS | • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD cohort) | PK parameters of SPG302 on concentrations in plasma | 7 days | 
| Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD food effect cohort) | Effects of food on SPG302 PK profile | 15 days | 
| Plasma pharmacokinetics of SPG302 in healthy volunteers (MAD cohort) | PK parameters of SPG302 on concentrations in plasma | 12 days | 
| Plasma pharmacokinetics of SPG302 in participants with ALS | PK parameters of SPG302 on concentrations in plasma | 60 days | 
| Clinical outcomes of multiple oral doses of SPG302 in participants with ALS | Spirometry | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, regenerative, synapse