Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001
Gantenerumab: Subcutaneously every 4 weeks at escalating doses
Solanezumab: Intravenous infusion every 4 weeks at escalating doses
Matching Placebo (Gantenerumab): Subcutaneous injection of placebo every 4 weeks
Matching Placebo (Solanezumab): Intravenous infusion of placebo every 4 weeks
Gantenerumab: Open-label administered Subcutaneously every 4 weeks at escalating doses
E2814: Administered intravenously in a blinded fashion
Lecanemab: Administered intravenously
Matching Placebo (E2814): Placebo administered intravenously in a blinded fashion.
Study summary
The purpose of this study is 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 slows the rate of progression of cognitive/clinical impairment or improves disease-related biomarkers.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
Accepted
Inclusion Criteria:
* Between 18-80 years of age
* Individuals who know they have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have dominantly inherited Alzheimer's disease (DIAD) mutation in their family.
* Are within -15 to + 10 years of the predicted or actual age of cognitive symptom onset. For Cognitive Run-In (CRI): includes participants who are younger than 15 years prior to the expected age of cognitive symptom onset, in addition to those 15 years younger and no more than 10 years older than expected 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, subject 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.
Exclusion Criteria:
* History or presence of brain MRI scans indicative of any other significant abnormality
* Alcohol or drug dependence 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)
Assess cognitive efficacy in individuals with mutations causing dominantly inherited AD as measured by the change from baseline in the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) — Baseline and Weeks 52, 104, 156, and 208 The DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) consists of 4 cognitive measures: Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test, Wechsler Adult Intelligence Sale Digit Symbol Substitution Test (WAIS), International Shopping List Task (ISLT), Mini-Mental State Examination (MMSE)
Trial sites (38)
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 Medical 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
The McCuster Foundation of Alzheimer's Disease Research
Nedlands
Western Australia
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo
Brazil
UBC Hospital
Vancouver
British Columbia
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
Niigata University Medical & Dental Hospital
Niigata
Niigata
University of Tokyo Hospital
Bunkyō City
Tokyo-To
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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