A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease

JRCT ID: jRCT2031230113

Registered date:07/06/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Dominantly Inherited Alzheimer's Disease
• Date of first enrollment: 19/02/2024
• Target sample size: 10
• Countries of recruitment: USA,Japan,Australia,Japan,Canada,Japan,UK,Japan,France,Japan,Spain,Japan,the Netherlands,Japan,Italy,Japan,Germany,Japan,Ireland,Japan,Argentine,Japan,Brazil,Japan,Mexico,Japan,Colombia,Japan,New Zealand,Japan
• Study type: Interventional

Intervention(s)

Drug: E2814, Specified dose on specified days
Administered intravenously in a blinded fashion

Drug: Lecanemab, Specified dose on specified days
Administered intravenously
Other Name: BAN2401

Outcome(s)

• Primary Outcome: 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

1. Symptomatic Population (Cohort 1): Key Secondary: Change from Week 24 to Week 208 in Clinical Dementia Scale - Sum of Boxes (CDR-SB). [ Time Frame: 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 outcomes
2. Asymptomatic Population (Cohort 2): Key Secondary: Change from Week 0 to Week 104 and Week 208 in CSF ptau217/total tau [ Time Frame: 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
3. Symptomatic Population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in the cognitive composite score [ Time Frame: Weeks 24, 52, 76, 104, 128, 156, 180 and 208 ]
4. Symptomatic Population (Cohort 1): Change from Week 0 to Week 24 in amyloid PET [ Time Frame: Week 0 to Week 24 ]
5. Asymptomatic Population (Cohort 2): Change from Week 0 to Week 52 in CSF ptau217/total tau [ Time Frame: Week 0 to Week 52 ]
6. Symptomatic population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in CSF neurofilament light chain (NfL) [ Time Frame: Weeks 24, 104 and 208 ]
7. Asymptomatic Population (Cohort 2): Change from Week 52 to Week 104 and Week 208 in CSF neurofilament light chain (NfL) [ Time Frame: Weeks 52, 104 and 208 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include 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.
- People of childbearing potential (POCBP), if partner is not sterilized, participant must agree to use highly effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, vasectomized partner).
- 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.

Exclude 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.

Related Information

• Primary Sponsor: Bateman J. Randall
• Secondary Sponsor: Eisai, Inc.
• Source(s) of Monetary Support: the United States National Institute on Aging (NIA) of the National Institutes of Health (NIH),Alzheimer's Association,GHR Foundation
• Secondary ID(s): NCT01760005,NCT05269394