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

• ClinicalTrials.gov Identifier: NCT05882695
• Recruitment Status: Recruiting
• First Posted: May 31, 2023
• Last Update Posted: May 7, 2024
• Sponsor: Spinogenix
• Collaborator: Novotech (Australia) Pty Limited
• Information provided by (Responsible Party): Spinogenix

Study Description

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

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: SPG302; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blinded
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 3, 2023
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability in healthy volunteers (SAD cohort) [ Time Frame: 7 days ]
   • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
2. Safety and tolerability in healthy volunteers (SAD food effect cohort) [ Time Frame: 15 days ]
   • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
3. Safety and tolerability in healthy volunteers (MAD cohort) [ Time Frame: 12 days ]
   • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
4. Safety and tolerability in participants with ALS [ Time Frame: 60 days ]
   • Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

Secondary Outcome Measures :

1. Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD cohort) [ Time Frame: 7 days ]
   PK parameters of SPG302 on concentrations in plasma
2. Plasma pharmacokinetics of SPG302 in healthy volunteers (SAD food effect cohort) [ Time Frame: 15 days ]
   Effects of food on SPG302 PK profile
3. Plasma pharmacokinetics of SPG302 in healthy volunteers (MAD cohort) [ Time Frame: 12 days ]
   PK parameters of SPG302 on concentrations in plasma
4. Plasma pharmacokinetics of SPG302 in participants with ALS [ Time Frame: 12mon ]
   PK parameters of SPG302 on concentrations in plasma
5. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   Spirometry
6. Clinical efficacy measures of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   The Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R).

Other Outcome Measures:

1. Effect of repeated dosing of SPG302 on electroencephalogram in healthy volunteers (MAD cohort) [ Time Frame: 12 mon ]
   Change from baseline in EEG parameters
2. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   Number of respiratory complications
3. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   Spirometry
4. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   TMS
5. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   EEG
6. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12 mon ]
   Change in Nocturnal Pulse Oximetry
7. Clinical outcomes of multiple oral doses of SPG302 in participants with ALS [ Time Frame: 12mon ]
   Edinburgh Cognitive and Behavioural ALS Screen (ECAS)
8. Effect of SPG302 on proteins and biomarkers in participants with ALS [ Time Frame: 12mon ]
   Multiple protein and immunological biomarkers
9. The effect of SPG302 on protein(s) and biomarkers [ Time Frame: 12mon ]
   Change from baseline in the analysis of Columbia-Suicide Severity Rating Scale (C-SSRS)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Public queries for healthy volunteers; +61 1800 243 733; melbourne@nucleusnetwork.com

Contact: Ofer M Gonen, MD; +61 3 8593 9800; o.gonen@nucleusnetwork.com.au

Locations

Australia, New South Wales

Macquarie University; Recruiting

North Ryde, New South Wales, Australia, 2109

Contact: Richard Gan +61 (2) 9812 3739 richard.gan@mq.edu.au

Contact: Paula Bayeh +612 9812 3049 paula.ordonezartunduaga@mq.edu.au

Principal Investigator: Dominic Rowe, MD

Australia, Queensland

Royal Brisbane and Women's Hospital; Recruiting

Herston, Queensland, Australia, 4029

Contact: Susan Heggie 07 3646 1478 Susan.Heggie@health.qld.gov.au

Contact: Kathryn Thorpe 07 3346 5011 kathryn.thorpe@health.qld.gov.au

Australia, South Australia

Flinders Medical center; Recruiting

Adelaide, South Australia, Australia, 5042

Contact: David Schultz, MD 8204 4187 david.schultz@sa.gov.au

Australia, Victoria

Nucleus Melbourne (healthy volunteers); Completed

Melbourne, Victoria, Australia, 3004

Sponsors and Collaborators

Spinogenix

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)
• Principal Investigator: Dominic Rowe, MD; Macquarie Hospital

More Information

• Responsible Party: Spinogenix
• ClinicalTrials.gov Identifier: NCT05882695
• Other Study ID Numbers: SPG302-ALS-001
• First Posted: May 31, 2023
• Last Update Posted: May 7, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Spinogenix:

Amyotrophic Lateral Sclerosis; regenerative; synapse

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases