AV-1959R Vaccine in Individuals With Preclinical Alzheimer's Disease

NCT07827768 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: US-AV1959R-201
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Preclinical Alzheimer's Disease; Alzheimer Disease

Keywords

AV-1959R; Amyloid-beta; Alzheimer's Vaccine; Secondary Prevention of Alzheimer's Disease; Alzheimer's Disease Prevention; Active Immunotherapy for Alzheimer's Disease

Outcome Measures

Primary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

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

  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.

  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.

  Through Week 78

• Change From Baseline in Columbia-Suicide Severity Rating Scale Suicidal Ideation Severity Score

  Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation severity score, comparing AV-1959R and placebo groups. The score ranges from 0 to 5, with higher scores indicating greater severity of suicidal ideation.

  Baseline and Weeks 4, 44, and 78

• Serum Anti-Amyloid-Beta Antibody Levels

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

  Baseline through Week 78

Secondary Outcomes (3)

• T-cell responses to MultiTEP and amyloid-beta

  Baseline through Week 78

• Change From Baseline in Global Brain Amyloid Burden

  Baseline to Week 78

• Change From Baseline in Plasma p-tau217/Aβ1-42 Ratio

  Baseline through Week 78

Other Outcomes (7)

• Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score

  Baseline to Week 78

• Change From Baseline in Plasma Amyloid Biomarkers

  Baseline through Week 78

• Change From Baseline in Plasma Tau Biomarker Concentrations

  Baseline through Week 78

Study Arms (2)

AV-1959R

EXPERIMENTAL

Participants will receive AV-1959R 100 micrograms with adjuvant by intramuscular injection at Weeks 0, 4, and 44.

Biological: AV-1959R

Placebo

PLACEBO COMPARATOR

Participants will receive placebo with adjuvant by intramuscular injection at Weeks 0, 4, and 44.

Drug: Placebo

Interventions

AV-1959R BIOLOGICAL

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

AV-1959R

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute for Molecular Medicine: lead
• Nuravax, Inc.: collaborator

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Agadjanyan

  Institute for Molecular Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roman Kniazev

CONTACT

7145963981; rkniazev@immed.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators will remain blinded to treatment assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 1:1 to AV-1959R or placebo

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 18, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): June 15, 2029
• Study Completion (Estimated): June 15, 2029
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share