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)
E2814: Administered intravenously in a blinded fashion
Lecanemab: Administered intravenously
Matching Placebo (E2814): Placebo administered intravenously in a blinded fashion.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
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). — 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).
Trial sites (36)
Facility
City
Region
Status
University of Alabama in Birmingham
Birmingham
Alabama
University of California San Diego Medical Center
La Jolla
California
USC Keck School of Medicine
Los Angeles
California
Yale University School of Medicine
New Haven
Connecticut
Emory University
Atlanta
Georgia
Advocate Lutheran General Hospital
Park Ridge
Illinois
Indiana University School of Medicine
Indianapolis
Indiana
Washington University in St. Louis
St Louis
Missouri
University of Pittsburgh
Pittsburgh
Pennsylvania
Butler Hospital
Providence
Rhode Island
Kerwin Research Center,
Dallas
Texas
University of Washington
Seattle
Washington
Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
Ciudad Autonoma de Buenos Aire
Argentina
Neuroscience Research Australia
Randwick
New South Wales
Alzheimer's Research Australia
Melbourne
Victoria
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo
Brazil
Sunnybrook Health Sciences Centre
Toronto
Ontario
McGill Center for Studies in Aging
Verdun
Quebec
CHU de Quebec - Hôpital de l' Enfant Jésus
Québec
Canada
Grupo de Neurociencias Sede de la Universidad de Antioquia
Medellín
Colombia
CHU de Toulouse - Hôpital Purpan
Toulouse
Haute Garonne
Hopital Roger Salengro - CHU Lille
Lille
Nord
Groupe Hospitalier Pitie-Salpetriere
Paris
Paris
Hopital Neurologique Pierre Wertheimer
Bron
Rhone
CHU de Rouen - Hôpital Charles Nicolle
Rouen
Seine Maritime
Universitaetsklinikum Tubingen
Tübingen
Baden-Wurttemberg
LMU-Campus Grosshadern
Munich
Bavaria
St Vincent's University Hospital
Dublin
Ireland
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Brescia
Italy
Azienda Ospedaliera Universitaria Careggi
Florence
Italy
University of Tokyo Hospital
Bunkyō City
Tokyo-To
Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
Mexico City
Mexico City
Brain Research Center
Amsterdam
Netherlands
University of Puerto Rico, School of Medicine
San Juan
Puerto Rico
Hospital Clínic I Provincial de Barcelona
Barcelona
Spain
The National Hospital for Neurology and Neurosurgery
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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