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.
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
Contacten en locaties
Studiecontact
- Naam: Roman Kniazev
- Telefoonnummer: 7145963981
- E-mail: rkniazev@immed.org
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Preventie
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Dubbele
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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-vergelijker: 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.
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Baseline through Week 78
|
Serum anti-amyloid-beta antibody levels following vaccination, comparing AV-1959R and placebo groups.
|
Baseline through Week 78
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
T-cell responses to MultiTEP and amyloid-beta
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Change From Baseline in CDR-SB Score
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Baseline through Week 78
|
Change from baseline in plasma neurofilament light chain (NfL).
|
Baseline through Week 78
|
|
Change From Baseline in Plasma GFAP
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Michael Agadjanyan, Institute for Molecular Medicine
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Psychische aandoening
- Pathologische aandoeningen, anatomisch
- Neurocognitieve stoornissen
- Dementie
- Tauopathieën
- Neurodegeneratieve ziekten
- Pathologische aandoeningen, tekenen en symptomen
- Ziekte van Alzheimer
- Plaque, amyloïde
Andere studie-ID-nummers
- US-AV1959R-201
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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