Phase 2 Study of AV-1959R in Individuals With Preclinical Alzheimer's Disease
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Roman Kniazev
- Phone Number: 7145963981
- Email: rkniazev@immed.org
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: AV-1959R
Participants will receive AV-1959R 100 micrograms with adjuvant by intramuscular injection at Weeks 0, 4, and 44.
|
Investigational amyloid-beta vaccine, AV-1959R, 100 micrograms, administered intramuscularly with adjuvant at Weeks 0, 4, and 44.
|
|
Placebo Comparator: Placebo
Participants will receive placebo with adjuvant by intramuscular injection at Weeks 0, 4, and 44.
|
Placebo administered by intramuscular injection with adjuvant at Weeks 0, 4, and 44.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
From first study intervention through Week 78
|
|
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.
|
Through Week 78
|
|
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.
|
Through Week 78
|
|
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.
|
Baseline through Week 78
|
|
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.
|
Baseline through Week 78
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Baseline through Week 78
|
|
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.
|
Baseline to Week 78
|
|
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.
|
Baseline through Week 78
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Baseline to Week 78
|
|
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.
|
Baseline through Week 78
|
|
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.
|
Baseline through Week 78
|
|
Change From Baseline in Plasma Neurofilament Light Chain
Time Frame: Baseline through Week 78
|
Change from baseline in plasma neurofilament light chain (NfL).
|
Baseline through Week 78
|
|
Change From Baseline in Plasma GFAP
Time Frame: Baseline through Week 78
|
Change from baseline in plasma glial fibrillary acidic protein (GFAP).
|
Baseline through Week 78
|
|
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.
|
Baseline to Week 78
|
|
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.
|
Baseline through Week 78
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Agadjanyan, Institute for Molecular Medicine
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- US-AV1959R-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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