Alzheimer's Tau Platform: Master Protocol

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 the anti-amyloid monoclonal antibody, donanemab, 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 a tau-directed therapy, alone or in combination with donanemab, reduce tau buildup in the brain compared to donanemab alone?
* Does a tau-directed therapy, alone or in combination with donanemab, slow disease progression based on brain imaging, fluid biomarkers, and measures of memory and thinking?

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 donanemab or placebo for 6 months, followed by 24 months of tau therapy alone or in combination with donanemab.
* 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 donanemab and tau therapy, or (3) donanemab 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 will launch with one regimen: Regimen A: AADvac1. In the future, Regimen B ("Tau2") will launch with a second tau directed therapy.

Conditions

• Preclinical Alzheimer's Disease
• Alzheimer Disease
• Prodromal Alzheimer's Disease

Interventions

DRUG

AADvac1

AADvac1 tau directed therapy

DRUG

Tau2

Tau2 directed therapy

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• University of California, San Francisco

  collaborator OTHER

• Massachusetts General Hospital

  collaborator OTHER

• Alzheimer's Therapeutic Research Institute

  collaborator OTHER

• Alzheimer's Clinical Trials Consortium

  collaborator OTHER

• Paul S. Aisen

  lead OTHER

Principal Investigators

• Adam Boxer, MD, PhD · University of California, San Francisco (UCSF), Memory and Aging Center

• Keith Johnson, MD · Massachusetts General Hospital (MGH), Harvard Medical School

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2028-08-31

Completion

2028-08-31

FDA Drug

Yes