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NCT Number: NCT07827768

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

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.

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Key information

Conditions

Preclinical Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Plaque, Amyloid Tauopathies

Age range

55 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

AV-1959R

Biological

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

Placebo

Drug

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

Primary outcomes

  1. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: From first study intervention through Week 78

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

  2. Incidence of ARIA-E and ARIA-H

    Time frame: Through Week 78

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

  3. Clinically Significant Changes in Safety Assessments

    Time frame: Through Week 78

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

  4. Change From Baseline in C-SSRS Score

    Time frame: Baseline through Week 78

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

  5. Serum Anti-Amyloid-Beta Antibody Levels

    Time frame: Baseline through Week 78

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

Secondary outcomes

  1. T-cell responses to MultiTEP and amyloid-beta

    Time frame: Baseline through Week 78

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

  2. Change From Baseline in Global Brain Amyloid Burden

    Time frame: Baseline to Week 78

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

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

    Time frame: Baseline through Week 78

    Change from baseline in plasma Lumipulse p-tau217/Aβ1-42 ratio, comparing the AV-1959R and placebo groups.

Other outcomes

  1. Change From Baseline in CDR-SB Score

    Time frame: Baseline to Week 78

    Change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, comparing the AV-1959R and placebo groups.

  2. Change From Baseline in Plasma Amyloid Biomarkers

    Time frame: Baseline through Week 78

    Change from baseline in plasma Aβ42, Aβ40, and Aβ42/Aβ40 ratio, comparing the AV-1959R and placebo groups.

  3. Change From Baseline in Plasma Tau Biomarkers

    Time frame: Baseline through Week 78

    Change from baseline in plasma BD-tau, MTBR-tau243, total tau, p-tau181, p-tau231, and p-tau217.

  4. Change From Baseline in Plasma Neurofilament Light Chain

    Time frame: Baseline through Week 78

    Change from baseline in plasma neurofilament light chain (NfL).

  5. Change From Baseline in Plasma GFAP

    Time frame: Baseline through Week 78

    Change from baseline in plasma glial fibrillary acidic protein (GFAP).

  6. Change From Baseline in Brain Tau Burden

    Time frame: Baseline to Week 78

    Change from baseline in pathological tau accumulation measured by quantitative tau PET imaging, comparing the AV-1959R and placebo groups.

  7. Changes in T-Cell and B-Cell Receptor Repertoires and Lineages

    Time frame: Baseline through Week 78

    Exploratory analysis of changes in T-cell receptor and B-cell receptor repertoires and T-cell and B-cell lineages in response to vaccination.

Study contacts

Contact information is provided by the study sponsor or research team.

Roman Kniazev

CONTACT

[email protected]

7145963981

Sponsors and collaborators

Lead sponsor

Institute for Molecular Medicine

Other

Collaborators

  • Nuravax, Inc.

Registry information

Official study title

A Phase II, Randomized, Double-Blind Study to Evaluate Safety, Tolerability, Immunogenicity, and Amyloid-Lowering Effect of Amyloid-β Vaccine, AV-1959R, in Individuals With Preclinical Alzheimer's Disease.

Important dates

Study start
2027
Primary completion
2029
Study completion
2029
First posted
Sep 18, 2026
Registry last updated
Sep 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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