A Phase I, Randomized, Double-Blind Study to Evaluate the Safety and Tolerability of AV-1980R in Participants With Preclinical Alzheimer's Disease
Institute for Molecular Medicine
Summary
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.
Description
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 obje…
Eligibility
- Age range
- 65–80 years
- Sex
- All
- Healthy volunteers
- No
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,…
Interventions
- BiologicalAV-1980R 20 µg
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.
- BiologicalAV-1980R 60 µg
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.
- BiologicalAV-1980R 180 µg
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.
- OtherPlacebo
10 mM phosphate buffer formulated with the adjuvant; intramuscular injections at Weeks 0, 4, 12, and 36; no active antigen.
Location
- Comprehensive Center for Brain HealthBoca Raton, Florida