Study of SPG302 in Adult Participants With Mild-to-Moderate Alzheimer's Disease (AD)

A Phase 2, Randomized, Placebo-controlled, Double-Blind Multicenter Study to Assess the Safety, Tolerability, and Pharmacodynamics (PD) in Adult Participants With Mild-to Moderate Alzheimer's Disease (AD) Administered SPG302

This phase 2 study will evaluate the safety, tolerability, clinical efficacy, pharmacokinetics, and pharmacodynamics of SPG302 in adult participants with mild-to-moderate AD.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: SPG302

Detailed Description

This is a phase 2, multicenter study to assess the safety, tolerability, CNS effects, pharmacokinetics, pharmacodynamics and clinical efficacy of SPG302 in adult participants with mild-to-moderate AD. The study will consist of 2 parts:

Part A: Placebo-controlled, randomized, safety and preliminary efficacy cohort with daily dosing for 28 day cycles

Part B: a randomized expansion cohort of daily dosing for 28 day cycles

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Flinders Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 45-85
• Diagnosis of mild to moderate AD
• Clinical laboratory values within normal range or < 1.5 times ULN
• If receiving AD-specific treatment, have been on stable dose for ≥ 3 months prior to first dose of study drug.
• Life expectancy of >2 years
• 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 that will not be resolved by first day of study intervention.
• History of clinically significant CNS event or diagnosis in the past 5 years.
• Acute illness within 30 days of Day 1
• History of suicidal behavior or suicidal ideation
• History of chronic alcohol use or substance abuse in the last 5 years
• HIV, hepatitis B and/or hepatitis C positive
• Vaccines within 14 days
• Receipt of investigational products within 30 days
• Blood donation within 30 days
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part A: Active SPG302 to be administered to adult participants with AD; Cohort 1: 12 participants with Alzheimer's Disease will be randomized in a 2:1 ratio to receive SPG302 or placebo. Study intervention will be 300 mg orally once daily for 28 days (cycle 1). All participants will receive open-label SPG302 for cycles 2-7. This arm may be expanded to cohort 2: 12 additional participants pending review of data, for additional dose exploration.	Drug: SPG302; synthetic small molecule
Placebo Comparator: Part A: Placebo comparator to be administered to adult participants with AD; Cohort 1: 12 participants with Alzheimer's Disease will be randomized in a 2:1 ratio to receive SPG302 or placebo. Study intervention will be placebo capsule orally daily for 28 days (cycle 1). All participants will receive open-label SPG302 for cycles 2-7. This arm may be expanded to 12 additional participants as cohort 2 pending review of data, for additional dose exploration.	Drug: Placebo; Placebo
Experimental: Part B: Expansion Cohort; Dose to be used and size of dosing cohort to be determined by Data Safety and Monitoring Committee following completion of Part A.	Drug: SPG302; synthetic small molecule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Electroencephalogram (EEG) at resting state and at auditory evoked P300 from baseline to endpoint	Electroencephalogram (EEG) will provide non-invasive measurement of brain activity. This test will be used to measure resting state cognitive activity as well as cognitive activity after auditory stimulation. Sound stimuli is 500Hz and 2000Hz.	8 months
Change in Alzheimer's Disease Assessment Scale-Cog (ADAS-COG) total score from baseline to endpoint	The Alzheimer's Disease Assessment Scale-Cognitive Subscale test (ADAS-Cog) measures language and memory, focusing on cognitive and non-cognitive functioning. It evaluates word recall, naming of objects, word recognition, comprehension and word finding. The ADAS-COG is scored 0-70. The higher the score the greater the impairment.	8 months
Change in Mini-Mental State Examination (MMSE) from baseline to endpoint	The Mini-Mental State Exam (MMSE) is a test of cognitive function. It includes tests of orientation, attention, memory, language and visual-spatial skills. The lower the score the greater the impairment.	8 months
C-SSRS (Columbia Suicide Severity Rating Scale)	Prospective suicidality assessment is performed using the Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire to evaluate suicidal ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section is considered positive. The suicidal behavior lethality sub-scale inquires about the level of actual or potential medical damage.	8 months
Change in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS - CGIC) from baseline to endpoint	The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS - CGIC) is a metric for clinical assessment of symptom severity. It consists of 2 parts. First a baseline evaluation of patient and caregiver is performed to collect necessary clinical information. The clinician will then conduct the second phase of the assessment after a specified time period, and changes in symptom severity are indicated on a seven point scale. A higher scale indicates a worsening of symptoms.	8 months
Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale from baseline to endpoint	The Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale is an scale that assesses the performance of daily tasks and activities. A lower score indicates lower functional performance.	8 months
Quality of Life in Alzheimer's Disease (QOL-AD) from baseline to endpoint	The Quality of Life in Alzheimer's Disease (QOL-AD) is a test to evaluate the quality of life through a series of questions of ability to complete daily activities and tasks. A lower score indicates lower functional quality of life.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of SPG302	Incidence, nature and severity of adverse events (AEs) and serious adverse events (SAEs)	8 months
Plasma pharmacokinetics of SPG302 in participants with AD-Maximum Plasma Concentration (Cmax)	Blood will be collected following administration of SPG302 and plasma levels will be evaluated to measure the maximum concentration.	8 months
Change in biomarkers in participants with AD from baseline to endpoint.	To assess the effect of SPG302 on Neurofilament light (NfL), a protein elevated in AD. This will be measured in picometers/milliliter.	8 months

Collaborators and Investigators

• Sponsor: Spinogenix
• Investigators: Principal Investigator: Lauren Priest, MBBS, Flinders Medical Center, Adelaide, SA, Australia; Principal Investigator: Brew Brew, MBBS,MD,DSC, St Vincents Hospital, Sydney, NSW, Australia

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 19, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Dementia; Alzheimer Disease; synapse; neural connectivity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: SPG302-ALZ-101

Drug and device information, study documents

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