## Protocol Section
### Identification Module
**NCT ID:** NCT06427668

**Brief Title:** Safety, Tolerability, and Efficacy of SPG302 in Adult Participants With Mild-to-Moderate Alzheimer's Disease (AD)

**Official Title:** 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

#### Organization Study ID Info
**ID:** SPG302-ALZ-101
#### Organization
**Class:** INDUSTRY
**Full Name:** Spinogenix
### Status Module
#### Completion Date
**Date:** 2026-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-19

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-19
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Spinogenix

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

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

**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

### Conditions Module

**Conditions:**

- Alzheimer Disease

**Keywords:**

- Alzheimer Disease

- synapse

- neural connectivity

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Phase 2 randomized, double-blind, placebo-controlled safety and tolerability study in adult participants with Alzheimer's Disease

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Double blinded

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 24

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: SPG302

**Label:** Part A: Active SPG302 to be administered to adult participants with AD

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Drug: Placebo

**Label:** Part A: Placebo comparator to be administered to adult participants with AD

**Type:** PLACEBO_COMPARATOR

#### Arm Group 3

**Description:** Dose to be used and size of dosing cohort to be determined by Data Safety and Monitoring Committee following completion of Part A.

**Intervention Names:**

- Drug: SPG302

**Label:** Part B: Expansion Cohort

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Part A: Active SPG302 to be administered to adult participants with AD

- Part B: Expansion Cohort

**Description:** synthetic small molecule

**Name:** SPG302

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Part A: Placebo comparator to be administered to adult participants with AD

**Description:** Placebo

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Change in Electroencephalogram (EEG) at resting state and at auditory evoked P300 from baseline to endpoint

**Time Frame:** 8 months

**Description:** 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.

**Measure:** Change in Alzheimer's Disease Assessment Scale-Cog (ADAS-COG) total score from baseline to endpoint

**Time Frame:** 8 months

**Description:** 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.

**Measure:** Change in Mini-Mental State Examination (MMSE) from baseline to endpoint

**Time Frame:** 8 months

**Description:** 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.

**Measure:** C-SSRS (Columbia Suicide Severity Rating Scale)

**Time Frame:** 8 months

**Description:** 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.

**Measure:** Change in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS - CGIC) from baseline to endpoint

**Time Frame:** 8 months

**Description:** 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.

**Measure:** Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale from baseline to endpoint

**Time Frame:** 8 months

**Description:** 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.

**Measure:** Quality of Life in Alzheimer's Disease (QOL-AD) from baseline to endpoint

**Time Frame:** 8 months

#### Secondary Outcomes

**Description:** Incidence, nature and severity of adverse events (AEs) and serious adverse events (SAEs)

**Measure:** Safety and tolerability of SPG302

**Time Frame:** 8 months

**Description:** Blood will be collected following administration of SPG302 and plasma levels will be evaluated to measure the maximum concentration.

**Measure:** Plasma pharmacokinetics of SPG302 in participants with AD-Maximum Plasma Concentration (Cmax)

**Time Frame:** 8 months

**Description:** To assess the effect of SPG302 on Neurofilament light (NfL), a protein elevated in AD. This will be measured in picometers/milliliter.

**Measure:** Change in biomarkers in participants with AD from baseline to endpoint.

**Time Frame:** 8 months

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 85 Years

**Minimum Age:** 45 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** aimee.cayzer@sa.gov.au

**Name:** Aimee Cayzer

**Phone:** +61 482 130 622

**Role:** CONTACT

**Contact 2:**

**Email:** lauren.priest@sa.gov.au

**Name:** L:auren Priest, MD

**Phone:** +61 419 385 015

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Flinders Medical Center

**Name:** Lauren Priest, MD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000003704

- Term: Dementia

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000024801

- Term: Tauopathies

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000019965

- Term: Neurocognitive Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M3885

- Name: Alzheimer Disease

- Relevance: HIGH

- As Found: Alzheimer's Disease

- ID: M6904

- Name: Dementia

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23002

- Name: Tauopathies

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21836

- Name: Neurocognitive Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: T2192

- Name: Familial Alzheimer Disease

- Relevance: HIGH

- As Found: Alzheimer's Disease

### Condition Browse Module - Meshes

- ID: D000000544

- Term: Alzheimer Disease

### Misc Info Module

- Version Holder: 2024-05-31
