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 (DIAN-TU)
Alzheimers Disease, Dementia, Alzheimers Disease, Familial
About this trial
This is an interventional treatment trial for Alzheimers Disease focused on measuring Alzheimer's, Alzheimer's Disease, Dementia, Mutation, Genetic Mutation, Dominantly Inherited Alzheimer's Disease, Dominantly Inherited Alzheimer Network, Autosomal Dominant Alzheimer's Disease, Early Onset Alzheimer's Disease, DIAN, DIAN-TU, DIAN TU, DIAD
Eligibility Criteria
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.
Sites / Locations
- University of Alabama in BirminghamRecruiting
- University of California San Diego Medical CenterRecruiting
- USC Keck School of MedicineRecruiting
- Yale University School of MedicineRecruiting
- Emory UniversityRecruiting
- Advocate Lutheran General HospitalRecruiting
- Indiana University School of MedicineRecruiting
- Washington University in St. LouisRecruiting
- University of PittsburghRecruiting
- Butler HospitalRecruiting
- Kerwin Medical CenterRecruiting
- University of WashingtonRecruiting
- Instituto de Investigaciones Neurologicas Raul Carrea, FLENIRecruiting
- Neuroscience Research AustraliaRecruiting
- Mental Health Research InstituteRecruiting
- The McCuster Foundation of Alzheimer's Disease Research
- Hospital das Clínicas da Faculdade de Medicina da USP
- UBC HospitalRecruiting
- Sunnybrook Health Sciences CentreRecruiting
- McGill Center for Studies in AgingRecruiting
- CHU de Quebec - Hôpital de l' Enfant JésusRecruiting
- Grupo de Neurociencias Sede de la Universidad de AntioquiaRecruiting
- CHU de Toulouse - Hôpital PurpanRecruiting
- Hopital Roger Salengro - CHU LilleRecruiting
- Groupe Hospitalier Pitie-SalpetriereRecruiting
- Hopital Neurologique Pierre WertheimerRecruiting
- CHU de Rouen - Hôpital Charles NicolleRecruiting
- Universitaetsklinikum Tubingen
- LMU-Campus Grosshadern
- St Vincent's University HospitalRecruiting
- IRCCS Centro San Giovanni di Dio FatebenefratelliRecruiting
- Azienda Ospedaliera Universitaria CareggiRecruiting
- University of Tokyo Hospital
- Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
- Brain Research CenterRecruiting
- University of Puerto Rico, School of MedicineRecruiting
- Hospital Clínic I Provincial de BarcelonaRecruiting
- The National Hospital for Neurology and NeurosurgeryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Placebo Comparator
Placebo Comparator
No Intervention
Active Comparator
Experimental
Experimental
Gantenerumab
Solanezumab
Matching placebo (Gantenerumab)
Matching Placebo (Solanezumab)
Cognitive Run-in
Gantenerumab Open Label Extension
E2814 plus lecanemab
Matching placebo (E2814) plus lecanemab
This arm completed and is closed.
This arm completed and is closed.
This arm completed and is closed.
This arm completed and is closed.
Subcutaneously every 4 weeks at escalating doses
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.
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.