Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation (DIAN-TU) (DIAN-TU)

February 11, 2026 updated by: Washington University School of Medicine

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

To assess the safety, tolerability, biomarker, cognitive, and clinical efficacy of investigational products in participants with an Alzheimer's disease-causing mutation by determining if treatment with the study drug improves disease-related biomarkers and slows the rate of progression of cognitive or clinical impairment.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Alzheimer's disease (AD) is characterized pathologically by the presence of accumulation of amyloid plaques and tau-containing neurofibrillary tangles (NFTs) in the brain. Amyloid plaques can be detectable within the brain some years before symptoms manifest whereas tau-mediated toxicity has been hypothesized to appear later during the course of disease. Physiologically, tau is predominantly a neuronal microtubule-associated protein that plays a fundamental role in the stabilization of microtubules. Under pathological conditions however, short motifs in the microtubule binding region (MTBR) domains of tau adopt a beta-sheet conformation, inducing self-assembly with other tau molecules that lead to the formation of insoluble aggregates. Insoluble tau is also a feature of a number of different neurodegenerative diseases collectively termed tauopathies. The accumulation of insoluble deposits has been suggested to result in altered distribution and function of organelles to adversely affect neuronal cell function as well as causing synapse loss, ultimately leading to cell death. In AD, evidence also suggests a direct correlation between the number of NFTs found in the brain at postmortem and the degree of dementia observed in subjects with AD at the time of death.

The microtubule-associated protein tau (MAPT) gene is located on chromosome 17 of the human genome. Through alternative splicing, 6 possible tau protein isoforms are expressed from this gene in the adult brain. A number of studies have suggested that pathological forms of tau protein transmit from neuron to neuron in human brain to cause disease, including AD. It has also been reported that tau can form seeds, which when applied extracellularly, can cause the initiation and propagation of intracellular tau aggregation. To form tau seeds, the MTBR of the protein is required. Furthermore, the tau MTBR is important in initiating the tau aggregation process and forming the core of fibrils pathologically associated with disease. Together, these observations suggest that therapeutic intervention with an antibody that binds to the MTBR region of tau in the brain, thereby disrupting tau aggregation may prevent initiation or slow down the neurodegeneration in AD or other tauopathies.

Upcoming Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trials are designed to investigate therapies targeting tau in combination with amyloid as pre-specified in the approved and NIH-funded NexGen Prevention Trial grants. As with other amyloid lowering drug trials, clinical benefit was not definitively demonstrated in the symptomatic population after tau pathology has been established. Determining the role of tau in disease biology and progression is critically important. Based on beneficial effects on amyloid, tau, and neurodegeneration markers associated with amyloid removal in the gantenerumab trial arm in DIAN-TU, the DIAN-TU will now implement amyloid removal treatment in mutation carriers and add placebo- controlled tau treatment arms. The platform trial design is exceptionally well-suited for the investigation of treatments used in combination because of ongoing multiple arms in a single trial and operational platform.

The current DIAN-TU amyloid removal drug arm has been extended to open-label extension (OLE) periods for prior participants. All enrolled participants who opted-in for OLE were unblinded to genetic status and offered open-label gantenerumab treatment. New treatment- naive mutation positive participants will be started on amyloid removal treatment with genetic counseling and testing. Therefore, all participants will be required to be positive for a dominantly inherited Alzheimer's disease (DIAD) mutation and will receive open-label treatment with lecanemab, an investigational amyloid removal drug, in combination with E2814, an anti-tau drug or placebo. Mutation non-carriers will not be enrolled. Specifically, all E2814 blinded drug arm participants will be treated with the lecanemab and randomized to either active E2814 tau therapy, or placebo.

The goal of the study is to investigate potential benefits of anti-tau therapy while anti-amyloid treatment is given as a background therapy. Furthermore, from ethical and participant recruitment perspectives, launching drug trials using amyloid and tau targeting therapies in combination may be essential, as participants and their families have expressed the need to have a drug that changes amyloid disease pathology in addition to being randomized to an investigational anti-tau drug (E2814) with uncertain benefit.

This record represents an analysis study portion of the Master Protocol Research Program (MPRP) under NCT01760005

Study Type

Interventional

Enrollment (Actual)

197

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma de Buenos Aire, Argentina, C1428AQK
        • Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Neuroscience Research Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3010
        • Alzheimer's Research Australia
  • Brazil
      • São Paulo, Brazil, 05403-000
        • Hospital das Clinicas da Faculdade de Medicina da USP
  • Canada
      • Québec, Canada, G1J 1Z4
        • CHU de Quebec - Hôpital de l' Enfant Jésus
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
    • Quebec
      • Verdun, Quebec, Canada, H4H 1R3
        • McGill Center for Studies in Aging
  • Colombia
      • Medellín, Colombia
        • Grupo de Neurociencias Sede de la Universidad de Antioquia
  • France
    • Haute Garonne
      • Toulouse, Haute Garonne, France, 31059
        • CHU de Toulouse - Hôpital Purpan
    • Nord
      • Lille, Nord, France, 59037
        • Hopital Roger Salengro - CHU Lille
    • Paris
      • Paris, Paris, France, 69677
        • Groupe Hospitalier Pitie-Salpetriere
    • Rhone
      • Bron, Rhone, France, 69677
        • Hôpital Neurologique Pierre Wertheimer
    • Seine Maritime
      • Rouen, Seine Maritime, France, 76031
        • CHU de Rouen - Hôpital Charles Nicolle
  • Germany
    • Baden-Wurttemberg
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Universitaetsklinikum Tubingen
    • Bavaria
      • Munich, Bavaria, Germany, 81377
        • LMU-Campus Grosshadern
  • Ireland
      • Dublin, Ireland, DUBLIN 4
        • St Vincent's University Hospital
  • Italy
      • Brescia, Italy, 25125
        • IRCCS Centro San Giovanni di Dio Fatebenefratelli
      • Florence, Italy, 50134
        • Azienda Ospedaliera Universitaria Careggi
  • Japan
    • Tokyo-To
      • Bunkyō City, Tokyo-To, Japan, 113-8655
        • University of Tokyo Hospital
  • Mexico
    • Mexico City
      • Mexico City, Mexico City, Mexico, 14269
        • Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
  • Netherlands
      • Amsterdam, Netherlands, 1081 GM
        • Brain Research Center
  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • University of Puerto Rico, School of Medicine
  • Spain
      • Barcelona, Spain, 8036
        • Hospital Clínic I Provincial de Barcelona
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, WC1B 3BG
        • The National Hospital for Neurology and Neurosurgery
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama in Birmingham
    • California
      • La Jolla, California, United States, 92037
        • University of California San Diego Medical Center
      • Los Angeles, California, United States, 90033
        • USC Keck School of Medicine
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory University
    • Illinois
      • Park Ridge, Illinois, United States, 60068
        • Advocate Lutheran General Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University school of Medicine
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02096
        • Butler Hospital
    • Texas
      • Dallas, Texas, United States, 75231
        • Kerwin Research Center,
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Between 18-80 years of age
  • Individuals who know they have an Alzheimer's disease-causing mutation.
  • Are within -10 to + 10 years of the predicted or actual age of cognitive symptom onset.
  • Cognitively normal or with mild cognitive impairment or mild dementia, Clinical Dementia Rating (CDR) of 0-1 (inclusive)
  • Fluency in DIAN-TU trial approved language and evidence of adequate premorbid intellectual functioning
  • Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations.
  • For women of childbearing potential, if partner is not sterilized, participant must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide).
  • Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
  • Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion.

Key Exclusion Criteria:

  • Significant neurologic disease (other than AD) or psychiatric disease that may currently or during the course of the study affect cognition or participant's ability to complete the study.
  • At high risk for suicide, e.g., significant suicidal ideation or attempt within last 12 months. Current stable mild depression or current use of antidepressant medications is not exclusionary.
  • History or presence of brain MRI scans indicative of any other significant abnormality
  • Substance or alcohol use disorder currently or within the past 1 year
  • Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin or body which would preclude MRI scan.
  • History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders
  • Anticoagulants except low dose (≤ 325 mg) aspirin.
  • Have been exposed to a monoclonal antibody targeting beta amyloid peptide within the past six months.
  • History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
  • Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial.
  • Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: E2814 plus lecanemab

Symptomatic Population (Cohort 1)

At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period.

At Week 24, participants randomized to E2814 will receive intravenously in a blinded fashion for the remainder of their treatment period.

Asymptomatic Population (Cohort 2)

At Week 0, participants randomized to E2814 will receive intravenously in a blinded fashion for the full treatment period.

At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.
Drug: E2814
Administered intravenously in a blinded fashion
Drug: Lecanemab
Administered intravenously
Other Names:
  • BAN2401
Placebo Comparator: Matching placebo (E2814) plus lecanemab

Symptomatic Population (Cohort 1)

At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period.

At Week 24, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the remainder of their treatment period.

Asymptomatic Population (Cohort 2)

At Week 0, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the full treatment period.

At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.
Drug: Lecanemab
Administered intravenously
Other Names:
  • BAN2401
Drug: Matching Placebo (E2814)
Placebo administered intravenously in a blinded fashion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary end point is the change from Week 24 to Week 104 and Week 208 in tau PET in the Symptomatic Population (Cohort 1).
Time Frame: Weeks 24, 104, and 208
To determine whether E2814 is superior to placebo, when each is concurrently administered with lecanemab, in the change from Week 24 to Week 104 (interim analysis) and Week 208 (final analysis) in tau spread as measured by tau PET in the symptomatic population (Cohort 1).
Weeks 24, 104, and 208

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptomatic Population (Cohort 1): Key Secondary: Change from Week 24 to Week 208 in Clinical Dementia Scale - Sum of Boxes (CDR-SB).
Time Frame: Weeks 24, 52, 104, 156 and 208

To determine whether E2814 is superior to placebo, when each is concurrently administered with lecanemab, in change from Week 24 to Week 208 in CDR-SB

Scores range from 0-18 with lower scores showing better outcomes
Weeks 24, 52, 104, 156 and 208
Asymptomatic Population (Cohort 2): Key Secondary: Change from Week 0 to Week 104 and Week 208 in CSF ptau217/total tau
Time Frame: Weeks 0, 104 and 208
To determine whether E2814 is superior to placebo, when each is administered alone and then concurrently with lecanemab, in change from Week 0 to Week 104 (interim analysis) and Week 208 (final analysis) in cerebrospinal fluid (CSF) phosphorylated tau (ptau217)/total tau
Weeks 0, 104 and 208
Symptomatic Population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in the cognitive composite score
Time Frame: Weeks 24, 52, 76, 104, 128, 156, 180 and 208
Weeks 24, 52, 76, 104, 128, 156, 180 and 208
Symptomatic Population (Cohort 1): Change from Week 0 to Week 24 in amyloid PET
Time Frame: Week 0 to Week 24
Week 0 to Week 24
Asymptomatic Population (Cohort 2): Change from Week 0 to Week 52 in CSF ptau217/total tau
Time Frame: Week 0 to Week 52
Week 0 to Week 52
Symptomatic population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in CSF neurofilament light chain (NfL)
Time Frame: Weeks 24, 104 and 208
Weeks 24, 104 and 208
Asymptomatic Population (Cohort 2): Change from Week 52 to Week 104 and Week 208 in CSF neurofilament light chain (NfL)
Time Frame: Weeks 52, 104 and 208
Weeks 52, 104 and 208

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

National Institute on Aging (NIA)
Alzheimer's Association
Eisai Inc.
Accelerating Medicines Partnership (AMP)

Investigators

  • Study Director: Randall J Bateman, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2021

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

January 13, 2022

First Submitted That Met QC Criteria

February 24, 2022

First Posted (Actual)

March 8, 2022

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 11, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DIAN-TU-001 (E2814)
  • The Alzheimer's Association (Other Grant/Funding Number: DIAN-TU-OLE-21-725093)
  • U01AG042791 (U.S. NIH Grant/Contract)
  • 2013-000307-17 (EudraCT Number)
  • R01AG046179 (U.S. NIH Grant/Contract)
  • REec-2014-0817 (Registry Identifier: Spanish Clinical Studies Registry)
  • GHR Foundation (Other Grant/Funding Number: File 4401)
  • Alzheimer's Association (Other Identifier: HDE 18S84914)
  • R56AG053267 (U.S. NIH Grant/Contract)
  • U01AG059798 (U.S. NIH Grant/Contract)
  • R01AG053267 (U.S. NIH Grant/Contract)
  • R01AG068319 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention [CAP REF].

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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