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)
Jared Brosch, MD
Primary Investigator
Brief description of study
What is the purpose of this study?
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 of study
What will happen during the study?
Participants should receive at least 3 doses at each titration step, 4 weeks (± 4 days) apart, before proceeding to the next titration step. The titration schema was designed to reach the target dose of 1500 mg Q4W; however, the target dose may not be achieved as otherwise dictated by amyloid-related imaging abnormalities vasogenic edema (ARIA-E) and hemorrhages (ARIA-H) management algorithms or more conservative action by the site PI/sponsor. Participants will receive the highest tolerated dose (up to 1500 mg Q4W).
At the start of Part 2, participants who were randomized to placebo in Part 1 will follow the same dose titration schedule and MRI safety schedule used in Part 1. Participants who were randomized to active drug in Part 1 will follow a mock dose titration and will have the same MRI safety schedule used during the initial drug titration as Part 1 but will remain on the dose that they were on at the end of Part 1. This will protect the blind to the original treatment assignment from Part 1. Participants, investigators, and the sponsor’s clinical team will remain blinded throughout the study to the Part 1 treatment assignment.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Alzheimers Disease, Dementia, Alzheimers Disease, Familial
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Age: 18 years - 80 years
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Gender: All
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.
