Study of SPG302 in Healthy Volunteers and ALS Participants

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

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

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

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