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

Not Applicable

Not yet recruiting

• Conditions: Alzheimer Disease; Preclinical Alzheimer's Disease
• Interventions: Biological: AV-1980R 20 µg; Biological: AV-1980R 60 µg; Biological: AV-1980R 180 µg; Other: Placebo

• Registration Number: NCT07158905
• Lead Sponsor: Institute for Molecular Medicine

Brief 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.

Detailed 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 objectives include immunogenicity measured by anti-tau antibody titers. Exploratory endpoints include plasma biomarker and tau-PET changes.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-27
• Study First Submitted QC: 2025-08-28
• Last Update Submitted: 2025-08-28
• Study First Posted: 2025-09-08
• Last Update Posted: 2025-09-08
• Study Start: 2025-12-15
• Primary Completion: 2029-06-15
• Study Completion: 2029-10-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AV-1980R 20 µg Arm	AV-1980R 20 µg	Participants receive 20 µg AV-1980R intramuscularly at Weeks 0, 4, 12, and 36.
AV-1980R 60 µg Arm	AV-1980R 60 µg	Participants receive 60 µg AV-1980R intramuscularly at Weeks 0, 4, 12, and 36.
AV-1980R 180 µg Arm	AV-1980R 180 µg	Participants receive 180 µg AV-1980R intramuscularly at Weeks 0, 4, 12, and 36.
Placebo Arm	Placebo	Participants receive placebo injections (10 mM phosphate buffer with the adjuvant, no antigen) at Weeks 0, 4, 12, and 36.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Baseline through Week 56	Frequency, severity, and relationship of TEAEs and SAEs; safety assessments include labs, vitals, ECGs, MRI, and neurological exams.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Clinically Significant Changes in Vital Signs	Baseline through Week 56	Number of participants with clinically significant abnormalities or changes in blood pressure, heart rate, respiratory rate, or body temperature.
Number of Participants with Clinically Significant Changes in ECG Results	Baseline through Week 56	Number of participants with new or worsening clinically significant ECG abnormalities.
Number of Participants with Clinically Significant Changes in Laboratory Tests	Baseline through Week 56	Number of participants with new or worsening abnormalities in hematology, serum chemistry, coagulation, or urinalysis results.
Incidence of Amyloid-Related Imaging Abnormalities (ARIA-E and ARIA-H)	Baseline through Week 56	Number of participants with vasogenic edema (ARIA-E), effusions, ischemic events, hemorrhagic events, or associated clinical symptoms detected on MRI.
Number of Participants with Clinically Significant Changes in Physical Examinations	Baseline through Week 56	Number of participants with new or worsening abnormal findings on physical examination.
Number of Participants with Clinically Significant Changes in Neurological Examinations	Baseline through Week 56	Number of participants with new or worsening abnormal neurological findings.
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline, Weeks 12, 36, 40, and 56	Change from baseline in suicidality assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS; range: 0-25, with higher scores indicating greater severity of suicidal ideation and behavior).
Change from Baseline in Serum Anti-Tau Antibody Concentrations	Baseline through Week 56	Quantification of anti-tau antibody titers induced by AV-1980R vaccination.
Detection of T Helper (Th) Cell Responses Specific to MultiTEP Platform	Baseline through Week 56	Presence of antigen-specific Th cell responses against the MultiTEP vaccine platform.
Detection of Autoreactive Th-Cell Responses Specific to Tau	Baseline through Week 56	Presence of autoreactive Th cell responses directed against tau epitopes.

Trial Locations

Locations (1)

Comprehensive Center for Brain Health; 🇺🇸 Boca Raton, Florida, United States