AV-1980R (Tau Vaccine) in Preclinical Alzheimer's Disease (TAURUS-1980)

Phase 1Not Yet RecruitingNCT07158905

Institute for Molecular Medicine48 enrolled

Overview

This is a Phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple dose-escalating trial to evaluate the safety, tolerability, and immune response of AV-1980R, an investigational vaccine targeting tau protein, in participants with preclinical Alzheimer's disease. Up to 48 cognitively unimpaired adults aged 65-80 with biomarker evidence of early Alzheimer's disease will be enrolled into three ascending dose cohorts. The study is designed as a secondary prevention trial to test whether therapeutic immunization at the preclinical stage is safe, induces an immune response, and, exploratorily, may favorably affect biomarkers associated with disease progression.

This first-in-human study investigates AV-1980R, a MultiTEP-based active immunotherapy formulated with the adjuvant, as a secondary prevention approach for Alzheimer's disease. The study will randomize up to 48 participants aged 65-80 years in a 3:1 ratio to AV-1980R or placebo across three ascending dose cohorts (20 μg, 60 μg, 180 μg). Participants will receive four intramuscular doses at Weeks 0, 4, 12, and 36, with follow-up through Week 56. Primary objectives are to evaluate safety and tolerability, monitored by adverse events, labs, ECGs, MRI, and neurological assessments. Secondary objectives include immunogenicity measured by anti-tau antibody titers. Exploratory endpoints include plasma biomarker and tau-PET changes.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Alzheimer Disease

Interventions

AV-1980R 20 µgBIOLOGICAL

MultiTEP-based investigational tau vaccine formulated with the adjuvant. The vaccine is designed to elicit anti-tau antibodies in participants with preclinical Alzheimer's disease.

AV-1980R 60 µgBIOLOGICAL

MultiTEP-based tau vaccine formulated with the adjuvant, 60 µg per dose; intramuscular injections at Weeks 0, 4, 12, and 36; secondary-prevention immunotherapy in preclinical AD.

AV-1980R 180 µgBIOLOGICAL

MultiTEP-based tau vaccine formulated with the adjuvant, 180 µg per dose; intramuscular injections at Weeks 0, 4, 12, and 36; secondary-prevention immunotherapy in preclinical AD.

PlaceboOTHER

10 mM phosphate buffer formulated with the adjuvant; intramuscular injections at Weeks 0, 4, 12, and 36; no active antigen.

Eligibility

Sex: ALLMin age: 65 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: Male or post-menopausal/surgically sterile female, 65-80 years of age. Cognitively unimpaired with preclinical Alzheimer's disease: CDR global score = 0. MMSE ≥ 26. WMS-R LM II ≥ 6. Amyloid Probability Score 2 (APS2) \> 54 (PrecivityAD2™). Adequate vision/hearing to comply with study procedures. Stable concomitant medications if applicable. Signed informed consent. Exclusion Criteria: MRI abnormalities: \>1 large lacunar infarct, territorial infarct, \>5 microbleeds, ARIA-E, or other significant pathology. Contraindications to MRI (e.g., pacemaker, metallic implants, severe claustrophobia). Serious illness or hospitalization within 4 weeks prior to enrollment. Clinically significant cardiovascular, endocrine, hematologic, autoimmune, or neurological disease. Insulin-dependent diabetes, significant arrhythmias, or seizure disorder. Positive C-SSRS (score ≥ 3). Prior tau or amyloid-beta immunotherapy within 1 year. Immunosuppressive or anticoagulant use that could interfere with study safety. Clinically significant lab abnormalities or positive HIV, HBV, or HCV screening.

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Frequency, severity, and relationship of TEAEs and SAEs; safety assessments include labs, vitals, ECGs, MRI, and neurological exams.