Secondary Prevention Trials

What is a secondary prevention trial?

Secondary prevention trials are studies aimed at stopping a disease from getting worse or causing further harm once it has already been detected. These trials usually involve people who already have early signs of a disease or are at high risk for developing it. In the context of Alzheimer’s disease (AD), these trials target AD pathology in asymptomatic or mild symptomatic individuals. While changes in the brain have begun at this point, “secondary prevention” efforts seek to intervene in the disease process before too much permanent damage is done.

The following studies focus on individuals who have a genetic likelihood to develop dominantly inherited Alzheimer’s disease (DIAD) at a young age, typically in their 30s, 40s, or 50s. Although there are differences between DIAD and the more common age-associated sporadic Alzheimer’s disease, the results of this study may have implications for future studies and treatments in sporadic Alzheimer’s disease.

About the Secondary Prevention Trials in Dominantly Inherited Alzheimer’s Disease

DIAN-TU-001 Trial (Tau NexGen): A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer’s Disease

Principal Investigator: Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine in St. Louis.

In 2012, the Dominantly Inherited Alzheimer Network Trials Unit (DIAN‐TU) at Washington University in St. Louis launched the first secondary prevention trial for Dominantly Inherited Alzheimer’s Disease (DIAD) families. The initial study drug arms tested in the trial were focused on amyloid-based therapies. In 2021, the DIAN-TU launched Tau Next Generation (Tau NexGen) prevention trial which will test three different experimental drugs focused on therapies that target tau.

The first tau study drug to be tested is known as E2814 and is designed to target tau tangles; in addition, an active anti-amyloid study drug called lecanemab (designed to target amyloid plaques) will also be administered. Both study drugs have been developed by Eisai Co., Ltd. and are investigational with lecanemab receiving marketing approval in several regions. This is the first Alzheimer’s prevention trial to target both tau tangles and amyloid plaques with two drugs at the same time. The research team continues to evaluate additional study drugs for the trial with expectations to add them in 2025 and/or 2026, and plans to choose from two classes of investigational tau drugs that act in different ways.

The trial’s goal is to determine the safety, tolerability, and effectiveness of each drug. The DIAN-TU secondary prevention trial will determine if these medications can prevent, delay, or possibly even reverse Alzheimer’s disease changes in the brain.

For additional information, please contact the DIAN Expanded Registry at dianexr@wustl.edu.   

DIAN-TU-003 (Amyloid Removal Trial): A Phase IIIb/IV Open-Label Study of Lecanemab to Evaluate Prevention and Progression of Dominantly Inherited Alzheimer’s Disease

Principal Investigator: Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine in St. Louis.

In 2012, the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University in St. Louis launched the first secondary prevention trial for Dominantly Inherited Alzheimer’s Disease (DIAD) families. The initial study drug arms, gantenerumab and solanezumab (both amyloid-based therapies) ended late 2019.  In mid-2020, the DIAN-TU continued treatment with gantenrumab in an open label extension study (OLE) which ended mid-2023. The DIAN-TU is now planning to launch the Amyloid Removal Trial (ART) with lecanemab, an active anti-amyloid study drug designed to target amyloid plaques. Approved by the FDA in 2023, lecanemab is the first traditionally approved treatment for patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease.

The DIAN-TU-003 ART is an open-label study to treat DIAD mutation carrier participants from the DIAN–TU-001 gantenerumab OLE period with lecanemab for a minimum of 5 years.  Participants will be co-enrolled in the Dominantly Inherited Alzheimer Network Observational (DIAN Obs) natural history study (NCT00869817) through which clinical, cognitive, imaging and fluid biomarker assessments will be conducted.

The main objectives of the 5-year DIAN-TU-003 ART are:

• To determine the effects of amyloid removal on age of symptom onset and clinical progression
• To determine if amyloid plaque can be fully removed in DIAD
• To determine the effects of amyloid removal on biomarkers of disease progression

The DIAN-TU-003 ART is an important study for the field of Alzheimer’s disease with the potential to answer key scientific questions regarding drug dose and duration, mechanism of action, safety, and optimal timing, exposure and effects of treatment to provide the greatest clinical benefit.  DIAN-TU-001 OLE participants were treated with the anti-amyloid therapy gantenerumab for 2 to 10 years, representing the longest treated group of patients with amyloid removing antibodies. Findings show that for this group of participants, overall, there was partial but not full amyloid removal.  The DIAN-TU-003 ART will enable continued evaluation of the long-term effects of amyloid removal on disease progression in these participants and may provide important information regarding whether removing amyloid plaques can delay, slow, or prevent symptom onset in DIAD.

For additional information, please contact the DIAN Expanded Registry at dianexr@wustl.edu.

For more information on DIAN-TU clinical trials

• View study details on www.clinicaltrials.gov 
• Read Frequently Asked Questions
• See the latest research updates 
• View participating sites 
• Meet the leadership team
• Learn about our funding