Clinical Research Directory

Alzheimer's Tau Platform: Master Protocol

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.

Alzheimer's Tau Platform: Regimen A - AADvac1

The Alzheimer's Tau Platform (ATP) is a multi-center platform trial to evaluate the safety and effectiveness of tau-directed therapies, alone or in combination with donanemab, in adults aged 50-80 with late preclinical or early prodromal Alzheimer's disease. Regimen A will evaluate the safety and efficacy of AADvac1, alone or in combination with donanemab.

AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid

The primary purpose of this study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial). This study will also evaluate the long-term safety and tolerability of lecanemab in participants enrolled in the Extension Phase.

A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease

The purpose of this study is to assess the effect of JNJ-64042056 on cognitive decline, as measured by Preclinical Alzheimer's disease Cognitive Composite 5 (PACC-5) compared with placebo.

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

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.

Alzheimer's Plasma Extension

The APEX study is a multicenter, observational study designed to capture longitudinal follow-up of plasma biomarkers and cognitive and functional assessments on individuals who screen failed in the AHEAD study over approximately 4 years. Approximately 1000 participants will be enrolled across three groups: * Group A: Approximately 500 participants who are discordant on screening (plasma positive / Positron Emission Tomography (PET) negative), * Group B: Approximately 250 participants who are concordant on screening (plasma negative / PET negative), and * Group C: Approximately 250 participants selected from the individuals who previously screen failed prior to PET for the AHEAD study with oversampling of racial and ethnic populations underrepresented in Alzheimer's disease (AD) clinical trials. Primary Objectives: * Collect longitudinal cognitive and functional assessments and blood-based biomarker data * Evaluate, characterize, and compare the longitudinal cognitive and functional data between the three groups of participants * Compare longitudinal change across race and ethnicity, sex, and Apolipoprotein E (ApoE) status Exploratory Objectives: • Collect baseline amyloid PET on participants without prior amyloid PET data (Group C)