E2814 + Lecanemab for Alzheimer's Disease

Recruiting at 33 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

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of the study is to determine the dose response of E2814, when concurrently administered with lecanemab, on the change from baseline at 18 months in cerebrospinal fluid (CSF) microtubule-binding region (MTBR)-tau-243 in participants with early Alzheimer's disease (AD).

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 lecanemab safe for humans?

Lecanemab has been studied for safety in people with Alzheimer's disease, and while it has shown some effectiveness in reducing brain amyloid-β (a protein linked to Alzheimer's), the safety data is primarily from trials with patients in the early stages of the disease. It is important to consult with a healthcare provider for personalized advice, as safety data for other conditions or stages is not available. ^{1 2 3 4 5}

How is the drug Lecanemab unique in treating Alzheimer's disease?

Lecanemab is unique because it is a monoclonal antibody (a type of protein made in the lab) that targets and clears amyloid-β, a protein that builds up in the brains of people with Alzheimer's, helping to slow down cognitive decline in early stages of the disease. ^{1 2 3 5 6}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Lecanemab: First Approval. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of lecanemab for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease. [2023]

6. New Zealand 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. [2023]