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
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
12 other identifiers
interventional
197
16 countries
36
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2021
Longer than P75 for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 22, 2021
CompletedFirst Submitted
Initial submission to the registry
January 13, 2022
CompletedFirst Posted
Study publicly available on registry
March 8, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2028
February 13, 2026
February 1, 2026
6.3 years
January 13, 2022
February 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
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 Outcomes (7)
Symptomatic Population (Cohort 1): Key Secondary: Change from Week 24 to Week 208 in Clinical Dementia Scale - Sum of Boxes (CDR-SB).
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
Weeks 0, 104 and 208
Symptomatic Population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in the cognitive composite score
Weeks 24, 52, 76, 104, 128, 156, 180 and 208
Symptomatic Population (Cohort 1): Change from Week 0 to Week 24 in amyloid PET
Week 0 to Week 24
Asymptomatic Population (Cohort 2): Change from Week 0 to Week 52 in CSF ptau217/total tau
Week 0 to Week 52
- +2 more secondary outcomes
Study Arms (2)
E2814 plus lecanemab
EXPERIMENTALSymptomatic 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.
Matching placebo (E2814) plus lecanemab
PLACEBO COMPARATORSymptomatic 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.
Interventions
Administered intravenously
Placebo administered intravenously in a blinded fashion.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Alzheimer's Associationcollaborator
- National Institute on Aging (NIA)collaborator
- Accelerating Medicines Partnership (AMP)collaborator
- Eisai Inc.collaborator
Study Sites (36)
University of Alabama in Birmingham
Birmingham, Alabama, 35294, United States
University of California San Diego Medical Center
La Jolla, California, 92037, United States
USC Keck School of Medicine
Los Angeles, California, 90033, United States
Yale University School of Medicine
New Haven, Connecticut, 06510, United States
Emory University
Atlanta, Georgia, 30329, United States
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
Washington University in St. Louis
St Louis, Missouri, 63110, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Butler Hospital
Providence, Rhode Island, 02096, United States
Kerwin Research Center,
Dallas, Texas, 75231, United States
University of Washington
Seattle, Washington, 98195, United States
Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
Ciudad Autonoma de Buenos Aire, C1428AQK, Argentina
Neuroscience Research Australia
Randwick, New South Wales, 2031, Australia
Alzheimer's Research Australia
Melbourne, Victoria, 3010, Australia
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo, 05403-000, Brazil
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
McGill Center for Studies in Aging
Verdun, Quebec, H4H 1R3, Canada
CHU de Quebec - Hôpital de l' Enfant Jésus
Québec, G1J 1Z4, Canada
Grupo de Neurociencias Sede de la Universidad de Antioquia
Medellín, Colombia
CHU de Toulouse - Hôpital Purpan
Toulouse, Haute Garonne, 31059, France
Hopital Roger Salengro - CHU Lille
Lille, Nord, 59037, France
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, 69677, France
Hopital Neurologique Pierre Wertheimer
Bron, Rhone, 69677, France
CHU de Rouen - Hôpital Charles Nicolle
Rouen, Seine Maritime, 76031, France
Universitaetsklinikum Tubingen
Tübingen, Baden-Wurttemberg, 72076, Germany
LMU-Campus Grosshadern
Munich, Bavaria, 81377, Germany
St Vincent's University Hospital
Dublin, DUBLIN 4, Ireland
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Brescia, 25125, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, 50134, Italy
University of Tokyo Hospital
Bunkyō City, Tokyo-To, 113-8655, Japan
Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
Mexico City, Mexico City, 14269, Mexico
Brain Research Center
Amsterdam, 1081 GM, Netherlands
University of Puerto Rico, School of Medicine
San Juan, 00936, Puerto Rico
Hospital Clínic I Provincial de Barcelona
Barcelona, 8036, Spain
The National Hospital for Neurology and Neurosurgery
London, Greater London, WC1B 3BG, United Kingdom
Related Publications (12)
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013 Feb;12(2):207-16. doi: 10.1016/S1474-4422(12)70291-0.
PMID: 23332364BACKGROUNDFitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, Crowther RA, Ghetti B, Goedert M, Scheres SHW. Cryo-EM structures of tau filaments from Alzheimer's disease. Nature. 2017 Jul 13;547(7662):185-190. doi: 10.1038/nature23002. Epub 2017 Jul 5.
PMID: 28678775BACKGROUNDFalcon B, Zhang W, Murzin AG, Murshudov G, Garringer HJ, Vidal R, Crowther RA, Ghetti B, Scheres SHW, Goedert M. Structures of filaments from Pick's disease reveal a novel tau protein fold. Nature. 2018 Sep;561(7721):137-140. doi: 10.1038/s41586-018-0454-y. Epub 2018 Aug 29.
PMID: 30158706BACKGROUNDKopeikina KJ, Hyman BT, Spires-Jones TL. Soluble forms of tau are toxic in Alzheimer's disease. Transl Neurosci. 2012 Sep;3(3):223-233. doi: 10.2478/s13380-012-0032-y.
PMID: 23029602BACKGROUNDBraak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.
PMID: 1759558BACKGROUNDGoedert M, Spillantini MG. Propagation of Tau aggregates. Mol Brain. 2017 May 30;10(1):18. doi: 10.1186/s13041-017-0298-7.
PMID: 28558799BACKGROUNDFalcon B, Cavallini A, Angers R, Glover S, Murray TK, Barnham L, Jackson S, O'Neill MJ, Isaacs AM, Hutton ML, Szekeres PG, Goedert M, Bose S. Conformation determines the seeding potencies of native and recombinant Tau aggregates. J Biol Chem. 2015 Jan 9;290(2):1049-65. doi: 10.1074/jbc.M114.589309. Epub 2014 Nov 18.
PMID: 25406315BACKGROUNDBarghorn S, Zheng-Fischhofer Q, Ackmann M, Biernat J, von Bergen M, Mandelkow EM, Mandelkow E. Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias. Biochemistry. 2000 Sep 26;39(38):11714-21. doi: 10.1021/bi000850r.
PMID: 10995239BACKGROUNDvon Bergen M, Friedhoff P, Biernat J, Heberle J, Mandelkow EM, Mandelkow E. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5129-34. doi: 10.1073/pnas.97.10.5129.
PMID: 10805776BACKGROUNDvon Bergen M, Barghorn S, Li L, Marx A, Biernat J, Mandelkow EM, Mandelkow E. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J Biol Chem. 2001 Dec 21;276(51):48165-74. doi: 10.1074/jbc.M105196200. Epub 2001 Oct 17.
PMID: 11606569BACKGROUNDSalloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, Hitchcock JM, Mills SL, Santacruz AM, Aschenbrenner AJ, Hassenstab J, Benzinger TLS, Gordon BA, Fagan AM, Coalier KA, Cruchaga C, Goate AA, Perrin RJ, Xiong C, Li Y, Morris JC, Snider BJ, Mummery C, Surti GM, Hannequin D, Wallon D, Berman SB, Lah JJ, Jimenez-Velazquez IZ, Roberson ED, van Dyck CH, Honig LS, Sanchez-Valle R, Brooks WS, Gauthier S, Galasko DR, Masters CL, Brosch JR, Hsiung GR, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Jack CR Jr, Koeppe R, Snyder PJ, Aisen PS, Thomas RG, Berry SM, Wendelberger BA, Andersen SW, Holdridge KC, Mintun MA, Yaari R, Sims JR, Baudler M, Delmar P, Doody RS, Fontoura P, Giacobino C, Kerchner GA, Bateman RJ; Dominantly Inherited Alzheimer Network-Trials Unit. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease. Nat Med. 2021 Jul;27(7):1187-1196. doi: 10.1038/s41591-021-01369-8. Epub 2021 Jun 21.
PMID: 34155411BACKGROUNDSandusky-Beltran LA, Sigurdsson EM. Tau immunotherapies: Lessons learned, current status and future considerations. Neuropharmacology. 2020 Sep 15;175:108104. doi: 10.1016/j.neuropharm.2020.108104. Epub 2020 Apr 28.
PMID: 32360477BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Randall J Bateman, MD
Washington University School of Medicine
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
Study Record Dates
First Submitted
January 13, 2022
First Posted
March 8, 2022
Study Start
December 22, 2021
Primary Completion (Estimated)
April 1, 2028
Study Completion (Estimated)
July 1, 2028
Last Updated
February 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
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 \[CAP REF\].