Phase 2 Study of AV-1959R in Individuals With Preclinical Alzheimer's Disease

Phase 2Not Yet RecruitingNCT07827768

Institute for Molecular Medicine160 enrolled

Overview

This Phase 2 study will evaluate the safety, tolerability, immunogenicity, and amyloid-lowering effect of AV-1959R in cognitively unimpaired adults with preclinical Alzheimer's disease. Approximately 160 participants will be randomized to receive AV-1959R or placebo and will be followed for 78 weeks. The study will assess safety, immune responses, brain amyloid, and Alzheimer's disease-related biomarkers.

This Phase 2 study is designed to further evaluate AV-1959R in cognitively unimpaired individuals with preclinical Alzheimer's disease, with emphasis on safety, tolerability, immunogenicity, and surrogate efficacy based on changes in Alzheimer's disease-related biomarkers and amyloid pathology

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

160

Conditions

Preclinical Alzheimer's Disease Alzheimer Disease

Interventions

AV-1959RBIOLOGICAL

Investigational amyloid-beta vaccine, AV-1959R, 100 micrograms, administered intramuscularly with adjuvant at Weeks 0, 4, and 44.

PlaceboDRUG

Placebo administered by intramuscular injection with adjuvant at Weeks 0, 4, and 44.

Eligibility

Sex: ALLMin age: 55 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: Male or female participants 55 to 80 years of age, inclusive, at screening. Signed informed consent before initiation of study-related procedures. Cognitively unimpaired participants with preclinical Alzheimer's disease meeting all of the following: CDR global score = 0 at screening. MMSE score ≥26 at screening, with education adjustment. Plasma p-tau217/Aβ1-42 ratio ≥0.00738. Vision and hearing sufficient to comply with study procedures, in the investigator's judgment. Stable concomitant medications for management of existing medical conditions, as appropriate. Women must be of non-childbearing potential as defined in the protocol. Men must meet protocol-defined contraception and sperm donation requirements. Ability, in the investigator's opinion, to understand the study and comply with study requirements. Exclusion Criteria: Screening MRI showing clinically significant abnormalities, including protocol-defined infarcts, excessive microbleeds, leptomeningeal hemosiderosis, superficial siderosis, or ARIA-E. Contraindication to MRI. Serious illness requiring systemic treatment and/or hospitalization within 4 weeks before study entry. Clinically relevant cardiovascular, respiratory, gastrointestinal, endocrine, immunologic, hematologic, neurologic, or other systemic disease that could interfere with participation or follow-up. Insulin-dependent diabetes. Clinically significant ECG abnormalities, including protocol-defined conduction abnormalities or QTc abnormalities. Pre-existing autoimmune disease. History of seizure disorder, except protocol-permitted use of certain antiepileptic medications for chronic pain. Any medical, psychological, or social condition that may interfere with participation, compliance, or safety. Participation in another investigational drug study or use of an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing. Prior amyloid-beta or tau immunotherapy, including vaccine or monoclonal antibody, within 1 year before screening. Recent use of protocol-defined immunomodulatory or growth-stimulating agents. Chronic use of protocol-defined anticoagulants or antiplatelet agents; aspirin is permitted. Parenteral use of immunoglobulin preparations, blood products, or plasma derivatives. History of severe local or systemic vaccine reactions or significant allergic reactions. Clinically significant laboratory abnormalities at screening. Positive testing for HIV-1/2, hepatitis B surface antigen, or hepatitis C virus.

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events (TEAEs)

Number and percentage of participants with treatment-emergent adverse events.

Time frame: From first study intervention through Week 78

Incidence of ARIA-E and ARIA-H

Number and percentage of participants with MRI-detected amyloid-related imaging abnormalities, including ARIA-E and ARIA-H.

Time frame: Through Week 78

Clinically Significant Changes in Safety Assessments

Number and percentage of participants with clinically significant changes in vital signs, ECG, laboratory assessments, physical examinations, or neurological examinations.

Time frame: Through Week 78

Change From Baseline in C-SSRS Score

Change from baseline in Columbia-Suicide Severity Rating Scale score comparing AV-1959R and placebo groups.

Time frame: Baseline through Week 78

Serum Anti-Amyloid-Beta Antibody Levels

Serum anti-amyloid-beta antibody levels following vaccination, comparing AV-1959R and placebo groups.

Time frame: Baseline through Week 78

Secondary Outcomes

T-cell responses to MultiTEP and amyloid-beta

Assessment of MultiTEP-specific T-cell responses and autoreactive anti-amyloid-beta T-cell responses, comparing AV-1959R and placebo groups.

Time frame: Baseline through Week 78

Change From Baseline in Global Brain Amyloid Burden

Change from baseline in global brain amyloid burden measured by amyloid PET using the Centiloid scale, comparing the AV-1959R and placebo groups.

Central Contacts

Roman Kniazev

CONTACT

7145963981 rkniazev@immed.org

Data from ClinicalTrials.gov

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