Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, regenerative, synapse
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
Interventions
DRUGSPG302
synthetic small molecule
DRUGPlacebo
Placebo
Sponsors
Novotech (Australia) Pty Limited
Spinogenix
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blinded
Intervention model description
Phase 1 randomized, double-blind, placebo-controlled, single, and multiple ascending dose study in HV and a repeat dose expansion in ALS cohort(s)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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
| Measure | Time frame | Description |
|---|---|---|
| Clinical outcomes of multiple oral doses of SPG302 in participants with ALS | 12 mon | Spirometry |
| 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 participants with ALS | 12mon | PK parameters of SPG302 on concentrations in plasma |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effect of repeated dosing of SPG302 on electroencephalogram in healthy volunteers (MAD cohort) | 12 mon | Change from baseline in EEG parameters |
| The effect of SPG302 on protein(s) and biomarkers | 12mon | Change from baseline in the analysis of Columbia-Suicide Severity Rating Scale (C-SSRS) |
| Effect of SPG302 on proteins and biomarkers in participants with ALS | 12mon | Multiple protein and immunological biomarkers |
| Clinical outcomes of multiple oral doses of SPG302 in participants with ALS | 12 mon | Number of respiratory complications |
Countries
Australia
Outcome results
None listed