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)
- Conditions
- Interventions
- Registration Number
- NCT05269394
- Lead Sponsor
- Washington University School of Medicine
- 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.
- 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. Phy...
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 197
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description E2814 plus lecanemab E2814 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. Matching placebo (E2814) plus lecanemab Matching Placebo (E2814) 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. E2814 plus lecanemab 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. Matching placebo (E2814) plus lecanemab 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.
- Primary Outcome Measures
Name Time Method 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).
- Secondary Outcome Measures
Name Time Method Symptomatic population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in CSF neurofilament light chain (NfL) Weeks 24, 104 and 208 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 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 outcomesSymptomatic 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 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 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
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 Asymptomatic Population (Cohort 2): Change from Week 52 to Week 104 and Week 208 in CSF neurofilament light chain (NfL) Weeks 52, 104 and 208
Trial Locations
- Locations (38)
Emory University
🇺🇸Atlanta, Georgia, United States
USC Keck School of Medicine
🇺🇸Los Angeles, California, United States
Grupo de Neurociencias Sede de la Universidad de Antioquia
🇨🇴Medellín, Colombia
St Vincent's University Hospital
🇮🇪Dublin, Ireland
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Mental Health Research Institute
🇦🇺Melbourne, Victoria, Australia
UBC Hospital
🇨🇦Vancouver, British Columbia, Canada
Hopital Roger Salengro - CHU Lille
🇫🇷Lille, Nord, France
Neuroscience Research Australia
🇦🇺Randwick, New South Wales, Australia
University of California San Diego Medical Center
🇺🇸La Jolla, California, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
University of Washington
🇺🇸Seattle, Washington, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Hospital das Clínicas da Faculdade de Medicina da USP
🇧🇷São Paulo, Brazil
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
McGill Center for Studies in Aging
🇨🇦Verdun, Quebec, Canada
CHU de Quebec - Hôpital de l' Enfant Jésus
🇨🇦Québec, Canada
CHU de Toulouse - Hôpital Purpan
🇫🇷Toulouse, Haute Garonne, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris cedex 13, Paris, France
Hopital Neurologique Pierre Wertheimer
🇫🇷Bron cedex, Rhone, France
Universitaetsklinikum Tubingen
🇩🇪Tübingen, Baden Wuerttemberg, Germany
CHU de Rouen - Hôpital Charles Nicolle
🇫🇷Rouen, Seine Maritime, France
LMU-Campus Grosshadern
🇩🇪Muenchen, Bayern, Germany
Brain Research Center
🇳🇱Amsterdam, Netherlands
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
IRCCS Centro San Giovanni di Dio Fatebenefratelli
🇮🇹Brescia, Italy
Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
🇲🇽Mexico, Distrito Federal, Mexico
Niigata University Medical & Dental Hospital
🇯🇵Niigata-shi, Niigata-Ken, Japan
Hospital Clínic I Provincial de Barcelona
🇪🇸Barcelona, Spain
University of Puerto Rico, School of Medicine
🇵🇷San Juan, Puerto Rico
The National Hospital for Neurology and Neurosurgery
🇬🇧London, Greater London, United Kingdom
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
University of Tokyo Hospital
🇯🇵Bunkyō-Ku, Tokyo-To, Japan
Kerwin Research Center,
🇺🇸Dallas, Texas, United States
University of Alabama in Birmingham
🇺🇸Birmingham, Alabama, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
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