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

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

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

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: SPG302

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

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ofer M Gonen, MD; Phone Number: +61 3 8593 9800; Email: o.gonen@nucleusnetwork.com.au
• Study Contact Backup: Name: Public queries for healthy volunteers; Phone Number: +61 1800 243 733; Email: melbourne@nucleusnetwork.com

Study Locations

• Australia
  • New South Wales
    • North Ryde, New South Wales, Australia, 2109
      • Not yet recruiting
      • Macquarie University
      • Principal Investigator: Dominic Rowe, MD
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Recruiting
      • Royal Brisbane and Women's Hospital
      • Contact: Susan Heggie; Phone Number: 07 3646 1478; Email: Susan.Heggie@health.qld.gov.au
      • Contact: Kathryn Thorpe; Phone Number: 07 3346 5011; Email: kathryn.thorpe@health.qld.gov.au
  • South Australia
    • Adelaide, South Australia, Australia, 5042
      • Recruiting
      • Flinders Medical Center
      • Contact: David Schultz, MD; Phone Number: 8204 4187; Email: david.schultz@sa.gov.au
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Completed
      • Nucleus Melbourne (healthy volunteers)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: SPG302; synthetic small molecule
Placebo Comparator: 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	Drug: Placebo; Placebo
Experimental: 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).	Drug: SPG302; synthetic small molecule
Placebo Comparator: 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).	Drug: Placebo; Placebo
Experimental: 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.	Drug: SPG302; synthetic small molecule
Placebo Comparator: 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.	Drug: Placebo; Placebo
Experimental: 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 12 cycles. A follow-up safety visit will be conducted 30 days after last dose (±7 days).	Drug: SPG302; synthetic small molecule

What is the study measuring?

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	12mon
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	Spirometry	12 mon
Clinical efficacy measures of SPG302 in participants with ALS	The Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R).	12 mon

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	Spirometry	12 mon
Effect of repeated dosing of SPG302 on electroencephalogram in healthy volunteers (MAD cohort)	Change from baseline in EEG parameters	12 mon
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	Number of respiratory complications	12 mon
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	TMS	12 mon
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	EEG	12 mon
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	Change in Nocturnal Pulse Oximetry	12 mon
Clinical outcomes of multiple oral doses of SPG302 in participants with ALS	Edinburgh Cognitive and Behavioural ALS Screen (ECAS)	12mon
Effect of SPG302 on proteins and biomarkers in participants with ALS	Multiple protein and immunological biomarkers	12mon
The effect of SPG302 on protein(s) and biomarkers	Change from baseline in the analysis of Columbia-Suicide Severity Rating Scale (C-SSRS)	12mon

Collaborators and Investigators

• Sponsor: Spinogenix
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Principal Investigator: Ofer M Gonen, MD, Nucleus Network (for healthy volunteers); Principal Investigator: David Schultz (ALS site), MD, Finders Medical Center (ALS); Principal Investigator: Robert Henderson (ALS site), MD, Royal Brisbane Hospital (ALS)

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; regenerative; synapse
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: SPG302-ALS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No