E2814 + Lecanemab for Alzheimer's Disease

Not currently recruiting at 46 trial locations

Overseen By Eisai Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eisai Inc.

Must be taking: Acetylcholinesterase inhibitors

Must not be taking: Antipsychotics, Anticoagulants

Disqualifiers: Neurological conditions, Stroke, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, E2814, combined with lecanemab (also known as Leqembi), for individuals with early Alzheimer's disease. Researchers aim to understand how these treatments affect certain brain proteins linked to Alzheimer's. Participants may receive varying doses of E2814 or a placebo (a harmless, inactive treatment) along with lecanemab. Suitable candidates for this trial include those diagnosed with mild cognitive impairment or mild Alzheimer's who have a study partner to support them throughout the trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants be on stable doses of any approved Alzheimer's medications for at least 12 weeks before starting. For other medications, they must be on stable doses for at least 4 weeks before the trial begins. If you are taking memantine and are in Japan, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lecanemab, when used alone, has been safe in past studies. It has helped slow memory and thinking problems in people with Alzheimer's disease and is generally well-tolerated. Early safety information supports further study of lecanemab, even in individuals with a specific genetic type of Alzheimer's.

For E2814, safety information when used with lecanemab is still being collected. Researchers are studying how these two treatments work together. This trial is in Phase 2, indicating that scientists are still learning about the treatment's safety and how well people tolerate it. Being in this phase suggests some initial safety information exists, but more is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Alzheimer's disease focus on managing symptoms with drugs like cholinesterase inhibitors or NMDA receptor antagonists. However, lecanemab is unique because it targets amyloid-beta plaques, a hallmark of Alzheimer's, aiming to slow disease progression rather than just managing symptoms. Researchers are also excited about the combination with E2814, as it represents a novel approach by potentially inhibiting tau propagation, another key factor in Alzheimer's pathology. By addressing both amyloid and tau, these treatments could offer a more comprehensive approach to tackling the disease.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research shows that lecanemab, one of the treatments in this trial, can help slow memory and thinking problems in people with early Alzheimer's. In a four-year study, participants taking lecanemab experienced less decline in mental abilities compared to those who did not take it. Lecanemab targets amyloid plaques, protein build-ups in the brain linked to Alzheimer's. E2814, another treatment option in this trial, targets tau, a different protein involved in Alzheimer's. Early research suggests that E2814 might reduce harmful tau proteins in the brain. This trial will explore using E2814 with lecanemab, potentially offering a new way to treat Alzheimer's by addressing both amyloid and tau proteins. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people aged 50-80 with early Alzheimer's, who score between 22 and 30 on the MMSE. They must meet criteria for probable AD dementia or MCI due to AD, have stable medication use, and a study partner available. Those on anticoagulants or unstable in other meds can't join.

Inclusion Criteria

I have been diagnosed with mild cognitive impairment likely due to Alzheimer's.

My memory issues are mild but noticeable.

I have been diagnosed with probable Alzheimer's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive E2814 or placebo as an IV infusion every four weeks and lecanemab as a SC injection every week for up to 18 months

18 months

IV infusion every 4 weeks, SC injection every week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lecanemab

Trial Overview

The trial tests E2814's effect on tau proteins in the brain when given with Lecanemab to those with early Alzheimer's. It measures changes after six months to see if it slows disease progression compared to a placebo.

How Is the Trial Designed?

Group I: Placebo + Lecanemab Experimental Treatment 2 Interventions

Participants will receive placebo administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Group II: E2814 Dose D + Lecanemab Experimental Treatment 2 Interventions

Participants will receive E2814 Dose D administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Group III: E2814 Dose C + Lecanemab Experimental Treatment 2 Interventions

Participants will receive E2814 Dose C administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Group IV: E2814 Dose B + Lecanemab Experimental Treatment 2 Interventions

Participants will receive E2814 Dose B administered as an IV infusion, Q4W along with lecanemab administered as a SC injection, QW.

Group V: E2814 Dose A + Lecanemab Experimental Treatment 2 Interventions

Participants will receive E2814 Dose A administered as an intravenous (IV) infusion, every four weeks (Q4W) along with lecanemab administered as a subcutaneous (SC) injection, every week (QW).

Lecanemab is already approved in United States, Japan for the following indications:

Approved in United States as Leqembi for:

• Early symptomatic Alzheimer's disease

Approved in Japan as Leqembi for:

• Early symptomatic Alzheimer's disease

Who Is Running the Clinical Trial?

Eisai Inc.

Lead Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

Lecanemab, an IgG1 antibody targeting amyloid-β, received its first approval for treating Alzheimer's disease in the USA on January 6, 2023, specifically for patients with mild cognitive impairment or mild dementia who have confirmed amyloid beta pathology.

The safety and effectiveness of lecanemab have only been established for the specific patient population studied in clinical trials, and there is no data on its use in earlier or later stages of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab: First Approval. Hoy, SM.[2023]

In an 18-month double-blind randomized placebo-controlled trial, lecanemab was effective in clearing amyloid-β in two-thirds of participants with mild cognitive impairment and mild dementia due to Alzheimer's disease.

Lecanemab also significantly reduced the rate of cognitive and functional decline in these individuals, suggesting its potential as a therapeutic intervention for early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab reduces brain amyloid-β and delays cognitive worsening. Knopman, DS.[2023]

Lecanemab, a monoclonal antibody targeting amyloid protofibrils, has shown significant efficacy in slowing the progression of Alzheimer's disease (AD) in an 18-month phase III trial, leading to improved cognitive and functional abilities in early AD patients.

The treatment is estimated to provide substantial long-term benefits, including a gain of 0.71 quality-adjusted life-years (QALYs) and a delay of nearly 3 years in progression to more severe stages of AD, highlighting its potential impact on patient quality of life and healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Path to Improved Alzheimer's Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer's Disease from the CLARITY AD Trial. Tahami Monfared, AA., Ye, W., Sardesai, A., et al.[2023]

Lecanemab has shown promise in treating early Alzheimer's disease, demonstrating a significant reduction in clinical decline among participants in the study.

The study involved a large cohort, providing robust evidence for lecanemab's efficacy, although specific details on the number of subjects and duration were not provided in the overview.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for lecanemab in early Alzheimer's disease. [2023]

Lecanemab demonstrated significant efficacy in slowing cognitive decline in patients with early Alzheimer's disease, as evidenced by improvements in multiple cognitive assessment scales across four randomized controlled trials involving 3,108 participants.

While lecanemab was associated with a reduction in amyloid burden, it also presented a risk of adverse events, particularly ARIA-E and ARIA-H, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of lecanemab for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. Qiao, Y., Chi, Y., Zhang, Q., et al.[2023]

Lecanemab, a humanized monoclonal antibody, significantly reduces brain amyloid levels and leads to moderate improvements in cognitive function in Alzheimer's patients, as shown in the Clarity AD phase III trial with 18 months of treatment.

While lecanemab demonstrates efficacy in slowing cognitive decline, it is associated with adverse events such as infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%), raising concerns about its administration and monitoring requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease. Park, J., Simpson, C., Patel, K.[2023]

Citations

1.

us.eisai.com

us.eisai.com/press-releases/eisai-to-present-the-latest-research-results-including-long-term-and-real-world-data-on-lecanemab-and-biomarkers-for-alzheimers-disease-at-the-adpd-2025-annual-meeting

Latest Lecanemab findings presented at AD/PD 2025 ...

These presentations will include the latest findings from real-world clinical evidence of lecanemab in the United States, efficacy and safety ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11114408/

Examining Phase III potential in Alzheimer's therapeutics - PMC

The primary objective of this survey is to introduce the succeeding contender after lecanemab (Leqembi). The featured drugs' mechanisms of ...

3.

prnewswire.com

prnewswire.com/news-releases/eisai-to-present-updated-dual-acting-lecanemab-data-research-on-blood-biomarkers-for-predicting-presence-of-amyloid-in-the-brain-and-new-findings-on-the-anti-mtbr-microtubule-binding-region-tau-antibody-e2814-at-the-17th-clinic-302285240.html

EISAI TO PRESENT UPDATED DUAL-ACTING ...

EISAI TO PRESENT UPDATED DUAL-ACTING LECANEMAB DATA, RESEARCH ON BLOOD BIOMARKERS FOR PREDICTING PRESENCE OF AMYLOID IN THE BRAIN AND NEW ...

4.

investors.biogen.com

investors.biogen.com/news-releases/news-release-details/early-alzheimers-patients-continue-benefit-four-years-leqembir

Early Alzheimer's Patients Continue to Benefit from Four ...

Over three years of treatment, including both the core study and the OLE, data showed lecanemab demonstrated a reduction in cognitive decline— ...

5.

eisai.com

eisai.com/news/2025/news202548.html

Eisai To Present Four-Year Efficacy And Safety Data On ...

Eisai To Present Four-Year Efficacy And Safety Data On Continuous Treatment With Lecanemab At The Alzheimer's Association International ...

6.

eisaimedicalinformation.com

eisaimedicalinformation.com/-/media/Files/EisaiMedicalInformation/Neurology/Congress-Materials/AAIC-2025/FRS-3rd-presentation_Baseline-Imaging-Characteristics-of-Participants-in-the-Phase-II_IIIDIAN-TU001-Tau-Nex-Gen-Trial-for-Dominantly-Inherited-Alzheimers-Disease.pdf?hash=43e15cc8-b381-46a4-b61d-94a43ccf6e9a

Anti-Tau Etalanetug (E2814) with Lecanemab Therapy in

• Preliminary safety data support continued evaluation of lecanemab in DIAD population. 59. AD, Alzheimer's disease. ApoE4, apolipoprotein E4 ...

7.

nature.com

nature.com/articles/s41392-024-01911-3

Recent advances in Alzheimer's disease: mechanisms ...

The trial aimed to evaluate the safety and efficacy of low-dose ladostigil (46) in patients with MCI. The results indicated that the drug was ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2274580725001086

Challenges and opportunities for novel combination ...

Three clinical trials combine anti-amyloid and anti-tau therapies. The combination of lecanemab and E2814 is being evaluated in the Dominantly Inherited ...

9.

nia.nih.gov

nia.nih.gov/news/nia-statement-report-lecanemab-reducing-cognitive-decline-alzheimers-clinical-trial

NIA statement on report of lecanemab reducing cognitive ...

The results show that lecanemab, an anti-amyloid antibody, slowed the rate of cognitive decline by 27% in an 18-month study involving participants experiencing ...