A Phase 2/3 interventional study of E2814 and Lecanemab in Alzheimers Disease, Dementia and Alzheimers Disease, Familial, sponsored by Washington University School of Medicine. Active, not recruiting at 36 sites in 16 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-07-27.
Sponsored by Washington University School of Medicine · Phase 2/3, Interventional, and Treatment
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.
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. Physiologically, tau is predominantly a neuronal microtubule-associated protein that plays a fundamental role in the stabilization of microtubules. Under pathological conditions however, short motifs in the microtubule binding region (MTBR) domains of tau adopt a beta-sheet conformation, inducing self-assembly with other tau molecules that lead to the formation of insoluble aggregates. Insoluble tau is also a feature of a number of different neurodegenerative diseases collectively termed tauopathies. The accumulation of insoluble deposits has been suggested to result in altered distribution and function of organelles to adversely affect neuronal cell function as well as causing synapse loss, ultimately leading to cell death. In AD, evidence also suggests a direct correlation between the number of NFTs found in the brain at postmortem and the degree of dementia observed in subjects with AD at the time of death.
The microtubule-associated protein tau (MAPT) gene is located on chromosome 17 of the human genome. Through alternative splicing, 6 possible tau protein isoforms are expressed from this gene in the adult brain. A number of studies have suggested that pathological forms of tau protein transmit from neuron to neuron in human brain to cause disease, including AD. It has also been reported that tau can form seeds, which when applied extracellularly, can cause the initiation and propagation of intracellular tau aggregation. To form tau seeds, the MTBR of the protein is required. Furthermore, the tau MTBR is important in initiating the tau aggregation process and forming the core of fibrils pathologically associated with disease. Together, these observations suggest that therapeutic intervention with an antibody that binds to the MTBR region of tau in the brain, thereby disrupting tau aggregation may prevent initiation or slow down the neurodegeneration in AD or other tauopathies.
Upcoming Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trials are designed to investigate therapies targeting tau in combination with amyloid as pre-specified in the approved and NIH-funded NexGen Prevention Trial grants. As with other amyloid lowering drug trials, clinical benefit was not definitively demonstrated in the symptomatic population after tau pathology has been established. Determining the role of tau in disease biology and progression is critically important. Based on beneficial effects on amyloid, tau, and neurodegeneration markers associated with amyloid removal in the gantenerumab trial arm in DIAN-TU, the DIAN-TU will now implement amyloid removal treatment in mutation carriers and add placebo- controlled tau treatment arms. The platform trial design is exceptionally well-suited for the investigation of treatments used in combination because of ongoing multiple arms in a single trial and operational platform.
The current DIAN-TU amyloid removal drug arm has been extended to open-label extension (OLE) periods for prior participants. All enrolled participants who opted-in for OLE were unblinded to genetic status and offered open-label gantenerumab treatment. New treatment- naive mutation positive participants will be started on amyloid removal treatment with genetic counseling and testing. Therefore, all participants will be required to be positive for a dominantly inherited Alzheimer's disease (DIAD) mutation and will receive open-label treatment with lecanemab, an investigational amyloid removal drug, in combination with E2814, an anti-tau drug or placebo. Mutation non-carriers will not be enrolled. Specifically, all E2814 blinded drug arm participants will be treated with the lecanemab and randomized to either active E2814 tau therapy, or placebo.
The goal of the study is to investigate potential benefits of anti-tau therapy while anti-amyloid treatment is given as a background therapy. Furthermore, from ethical and participant recruitment perspectives, launching drug trials using amyloid and tau targeting therapies in combination may be essential, as participants and their families have expressed the need to have a drug that changes amyloid disease pathology in addition to being randomized to an investigational anti-tau drug (E2814) with uncertain benefit.
This record represents an analysis study portion of the Master Protocol Research Program (MPRP) under NCT01760005
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 197 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
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Key Inclusion Criteria:
Key Exclusion Criteria:
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.
Drug: E2814 · Drug: 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.
Drug: Lecanemab · Drug: Matching Placebo (E2814)
Administered intravenously in a blinded fashion
Administered intravenously
Also known as: BAN2401
Placebo administered intravenously in a blinded fashion.
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).
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).
Time frame: 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).
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
Time frame: Weeks 24, 52, 104, 156 and 208
Asymptomatic Population (Cohort 2): Key Secondary: Change from Week 0 to Week 104 and Week 208 in CSF ptau217/total tau
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
Time frame: Weeks 0, 104 and 208
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
Symptomatic Population (Cohort 1): Change from Week 0 to Week 24 in amyloid PET
Time frame: Week 0 to Week 24
Asymptomatic Population (Cohort 2): Change from Week 0 to Week 52 in CSF ptau217/total tau
Time frame: Week 0 to Week 52
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
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
Plan to share: Yes — Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention \[CAP REF\].
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Washington University School of Medicine