Alzheimer's Tau Platform: Master Protocol

NCT06957418 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ATRI-014R01AG078457
• Study Type: interventional
• Target: 750
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of the Alzheimer's Tau Platform (ATP) is to evaluate the safety and effectiveness of tau-directed therapies, alone or in combination with an anti-amyloid monoclonal antibody (mAb), in adults aged 50-80 with late preclinical or early prodromal Alzheimer's disease. This platform trial allows for the simultaneous testing of multiple tau therapies under a shared master protocol. This means that multiple investigational products will be tested simultaneously or sequentially. Each investigational product will be tested in a regimen. The main questions the platform trial aims to answer are:

• Does any tau-directed therapy, alone or in combination with an anti-amyloid mAb, reduce brain tau deposition more than an anti-amyloid mAb, alone?
• Does any tau-directed therapy, alone or in combination with an anti-amyloid mAb, slow disease progression based on fluid biomarkers, imaging, or clinical measures? Participants will:
• Be randomized to a treatment regimens, each containing different tau therapies. The exact number of treatment regimens that will active at the time of screening will change over time.
• Receive an anti-amyloid mAb or placebo for 6 months, followed by 24 months of tau therapy alone or in combination with an anti-amyloid mAb.
• Undergo regular cognitive testing, brain scans (MRI/PET), and biomarker assessments over 30 months Participants will have an equal chance to be randomized to all regimens that are active at the time of screening. Once randomized to a regimen, participants will be randomized to one of three arms: (1) tau therapy alone, (2) a combination of an anti-amyloid mAb and tau therapy, or (3) an anti-amyloid mAb alone. New regimens will be continuously added as new investigational products become available. The Alzheimer's Tau Platform Trial will enroll additional participants as each new regimen becomes available. ATP is expected to launch with two regimens:
• Regimen A: AADvac1
• Regimen B: Tau2

Conditions

Prodromal Alzheimer's Disease; Preclinical Alzheimer's Disease; Alzheimer Disease

Keywords

Alzheimer's disease; Preclinical Alzheimer's; Prodromal Alzheimer's; Mild cognitive impairment (MCI); Neurodegeneration; Dementia; Tau-directed therapy; Monoclonal antibody; Anti-tau therapy; Combination therapy; Immunotherapy; anti-amyloid mAb

Outcome Measures

Primary Outcomes (1)

• Reduction of brain tau deposition as measured by tau positron emission tomography (PET)

  To determine whether at least one tau therapy, either alone or in combination with an anti-amyloid monoclonal antibody (mAb), will produce a greater reduction in brain tau deposition as measured by 18F-MK-6240 PET compared to anti-amyloid mAb alone.

  0, 6, 18 and 30 months

Secondary Outcomes (1)

• Disease progression as measured by plasma biomarkers

  30 months

Study Arms (2)

Regimen A: AADvac1

EXPERIMENTAL

Participants are randomized to receive either AADvac1, a tau directed monotherapy, combination AADvac1 with an anti-amyloid monoclonal antibody (mAb), or an anti-amyloid mAb alone (active control)

Drug: AADvac1

Regimen B: Tau2

EXPERIMENTAL

Participants are randomized to receive either Tau2 directed monotherapy, combination Tau2 directed therapy with an anti-amyloid monoclonal antibody (mAb), or an anti-amyloid mAb alone (active control)

Drug: Tau2

Interventions

AADvac1 DRUG

AADvac1 tau directed therapy

Regimen A: AADvac1

Tau2 DRUG

Tau2 directed therapy

Regimen B: Tau2

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentation of the participant's informed consent to study procedures (including APOE genotyping).
• Ages 50-80 years (inclusive). Participants between the ages of 50 and 60 (inclusive) must be mildly impaired at screening (global CDR=0.5 and maximum CDR-SB \<1.5
• Cognitively unimpaired (preclinical AD with a global CDR=0) or mildly impaired (prodromal AD with a global CDR=0.5 and maximum CDR-SB \<1.5).
• MMSE score at screening of 20-30 (inclusive) with educational adjustments:
• If \<12 years of education, MMSE required to be \>20.
• If 13 to 15 years (inclusive) of education, MMSE required to be \>22.
• If \>16 years of education, MMSE required to be \>24.
• Plasma biomarker result at screening that demonstrate the presence of amyloid pathology, consistent with preclinical-prodromal AD.
• Elevated brain tau on PET (MTL or NEO tau SUVr \>1.2) at screening.
• Elevated brain amyloid on PET (centiloids \> 40) at screening.
• Stable doses of permitted medications as described per protocol for a minimum of 30 days prior to screening.
• Resides at home or in the community (assisted living acceptable).
• In the opinion of the site PI, has a study partner able and willing to provide accurate information (including clinical symptoms and medical history) about the participant and participate in study visits and informant-based assessments (usually requires at least 5 hours of contact per week) for the duration of the study.
• As assessed by the site PI, participant is likely to be able to comply with the protocol for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy (English or Spanish) sufficient for compliance with the required testing procedures.
• Must complete all screening evaluations as outlined per protocol.

You may not qualify if:

• Females who are lactating or pregnant (as documented by a urine pregnancy test) during screening, or plan to become pregnant during the study.
• Females of childbearing potential who did not use a highly effective method of contraception within 28 days of screening and/or are not willing to use highly effective method of contraception for the duration of their participation in the study. Males who are sexually active with a female of childbearing potential and do not agree to use barrier methods of contraception (condoms with spermicide) during the trial and for 6 months after the last dose of study drug unless the female is using a highly effective method of contraception.
• Lacks good venous access such that multiple blood draws would be precluded.
• Weighs less than 40kg, or more than 136kg at screening.
• Suspected or known allergic reactions, adverse reactions, or hypersensitivity to any components of the study intervention for any of the available regimen.
• Previous treatment with the study intervention from any available regimen unless it can be confirmed the participant received placebo in the previous study.
• Prior or current treatment with a prohibited medication as described per protocol.
• Enrollment in another investigational study as described per protocol. Participants enrolled in an observational study may be permitted with Medical Monitor review and approval.
• Contraindications to MRI studies, including metal (ferromagnetic) implants, a cardiac pacemaker that is not compatible with MRI, and/or severe claustrophobia.
• Contraindications to tau and/or amyloid PET scan imaging and/or use of MK6240 and/or 18F-NAV-4694 (flutafuranol).
• For participants undergoing an LP as part of the optional longitudinal CSF biomarker sub-study, contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) \>1.4 or other coagulopathy; platelet count of \<120,000/μL; infection at the desired lumbar puncture site; taking anti-coagulant medication within 90 days of LP NOTE: low dose aspirin is permitted; degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
• Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of study drug (e.g., moderate and/or severe untreated obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular conditions), as per the site PI's judgement.
• History of severe allergic reaction (e.g., anaphylaxis) including, but not limited to: severe allergic reaction to previous vaccines, foods, and/or medications.
• Hospitalization within 30 days prior to screening or baseline.
• Clinically significant infections or major surgical operation within 3 months prior to screening.

Sponsors & Collaborators

• University of California, San Francisco: collaborator
• Massachusetts General Hospital: collaborator
• Alzheimer's Therapeutic Research Institute: collaborator
• Alzheimer's Clinical Trials Consortium: collaborator
• Paul S. Aisen: lead
• National Institute on Aging (NIA): collaborator

Related Links

• ACTC Alzheimer's Tau Platform

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Nerve Degeneration; Dementia

Interventions

AADvac1

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Adam Boxer, MD, PhD

  University of California, San Francisco (UCSF), Memory and Aging Center

  PRINCIPAL INVESTIGATOR

• Keith Johnson, MD

  Massachusetts General Hospital (MGH), Harvard Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ATP Recruitment and Retention (RER) Team

CONTACT

213-821-0569; adtau-participate@usc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, ATRI

Model Details: As new investigational products become available, additional regimens will be added to the Alzheimer's Tau Platform trial.

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: May 4, 2025
• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL