Preclinical Alzheimer's DiseasePhase 2AREVIANCT07827768
AV-1959R Vaccine in Individuals With Preclinical Alzheimer's Disease
A Phase 2 study testing AV-1959R in people with Preclinical Alzheimer's Disease and Alzheimer Disease, run by Institute for Molecular Medicine.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Preclinical Alzheimer's Disease, Alzheimer Disease
- What is being tested?
- AV-1959R
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2027to 15 Nov 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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. WMS-R LM2 score ≥ 6 Plasma p-tau217/Aβ1-42 ratio ≥0.00738. Brain amyloid burden ≥ 20CL. 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official 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.
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.
Read the detailed description
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
- Conditions
- Preclinical Alzheimer's Disease, Alzheimer Disease
- Being tested
- AV-1959R, Placebo
- Keywords
- AV-1959R, Amyloid-beta, Alzheimer's Vaccine, Secondary Prevention of Alzheimer's Disease, Alzheimer's Disease Prevention, Active Immunotherapy for Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| AV-1959R | Experimental | Participants will receive AV-1959R 100 micrograms with adjuvant by intramuscular injection at Weeks 0, 4, and 44. Receives: Biological: AV-1959R |
| Placebo | Placebo comparator | Participants will receive placebo with adjuvant by intramuscular injection at Weeks 0, 4, and 44. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Number and percentage of participants with treatment-emergent adverse events.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline through Week 78
Secondary outcomes (3)
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.
Measured: 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.
Measured: Baseline to Week 78
Change From Baseline in Plasma p-tau217/Aβ1-42 Ratio
Change from baseline in plasma Lumipulse p-tau217/Aβ1-42 ratio, comparing the AV-1959R and placebo groups.
Measured: Baseline through Week 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2026
- Study start1 Oct 2027 (estimated)
- Primary completion15 Oct 2029 (estimated)
- Study completion15 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preclinical Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized 1:1 to AV-1959R or placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute for Molecular Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Nuravax, Inc.
- Responsible party
- Sponsor
- Investigators
- Michael Agadjanyan, Principal investigator, Institute for Molecular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07827768
- Sponsor's protocol ID
- US-AV1959R-201
- Acronym
- AREVIA
- Status last verified
- Oct 2026
- First submitted
- 14 Sep 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data are not planned to be shared.