Investigational Alzheimer's Drugs for Early Onset Alzheimer's Disease

(DIAN-TU Trial)

Recruiting at 39 trial locations

Overseen By Diana Kerwin

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Monoclonal antibodies

Disqualifiers: Neurologic, Psychiatric, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 208 weeks

197 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests two drugs, lecanemab and E2814, in people with a genetic mutation that causes Alzheimer's disease. Lecanemab helps remove harmful protein clumps from the brain, while E2814 prevents harmful protein tangles from forming. The goal is to see if these drugs can slow down or improve symptoms of Alzheimer's.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain anticoagulants (blood thinners) except for low-dose aspirin, or if you have used a specific type of Alzheimer's treatment in the past six months.

What data supports the effectiveness of the drug Lecanemab for treating early onset Alzheimer's disease?

Research shows that Lecanemab can clear amyloid-β (a protein linked to Alzheimer's) in the brain and slow down the worsening of memory and thinking skills in people with mild Alzheimer's disease. ^{1 2 3 4 5}

What safety information is available for lecanemab (Leqembi) in treating Alzheimer's disease?

Lecanemab has been associated with some safety concerns, including amyloid-related imaging abnormalities (ARIA), which are usually without symptoms but can sometimes be serious or rarely fatal. There is also a risk of bleeding, especially in patients taking blood thinners, and those with a specific genetic marker (APOE4) may be at higher risk for ARIA. ^{1 2 3 4 6}

What makes the drug lecanemab unique for treating early 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, and it is specifically approved for early stages of the disease. It has been shown to reduce brain amyloid-β and slow down cognitive decline in patients with mild cognitive impairment or mild dementia. ^{1 4 5 6 7}

Research Team

Randall J Bateman, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals aged 18-80 who have a genetic mutation causing early onset Alzheimer's, are within -10 to +10 years of their predicted age of symptom onset, and can perform required tests (MRI, LP, PET). They must be cognitively normal or mildly impaired and have a reliable study partner. Women must use contraception if applicable.

Inclusion Criteria

I know I carry a gene mutation linked to Alzheimer's disease.

I can see and hear well enough to complete tests.

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)

Exclusion Criteria

I haven't had cancer in the last 5 years, except for certain skin or prostate cancers that haven't worsened.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label lecanemab and are randomized to E2814 or placebo, administered intravenously

208 weeks

Regular visits for intravenous administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term with open-label gantenerumab

Long-term

Treatment Details

Interventions

• E2814
• Lecanemab
• Matching Placebo (E2814)

Trial Overview The trial is testing Lecanemab and E2814 against a placebo to see if they improve Alzheimer's biomarkers and slow cognitive decline. Participants will receive either the investigational drugs or placebo to assess safety, tolerability, and effectiveness.

Participant Groups

Group I: E2814 plus lecanemab Experimental Treatment 2 Interventions

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.

Group II: Matching placebo (E2814) plus lecanemab Placebo Group 2 Interventions

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.

E2814 is already approved in United States for the following indications:

Approved in United States as E2814 for:

• Early Onset Alzheimer's Disease

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Accelerating Medicines Partnership (AMP)

Collaborator

Trials

3

Recruited

880+

Eisai Inc.

Industry 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, 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]

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 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]

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 is approved for early Alzheimer's disease treatment and its use in real-world settings requires careful adherence to safety guidelines, particularly monitoring for adverse events like amyloid-related imaging abnormalities (ARIA) and infusion reactions.

Patients with the APOE4 gene, especially homozygotes, are at a higher risk for ARIA, making genetic testing important for risk assessment before starting lecanemab, along with ensuring clinician preparedness for managing potential serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab: Appropriate Use Recommendations. Cummings, J., Apostolova, L., Rabinovici, GD., et al.[2023]

Lecanemab, a monoclonal antibody approved for Alzheimer's disease, has been shown to effectively reduce beta-amyloid accumulation and slow cognitive decline in 2729 participants across three clinical trials.

The treatment was well tolerated, with common side effects including headaches and infusion reactions, indicating a favorable safety profile while demonstrating significant improvements in various cognitive assessment scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer's disease: A systematic review. Chowdhury, S., Chowdhury, NS.[2023]

References

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

Lecanemab: First Approval. [2023]

2. 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]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Lecanemab: Appropriate Use Recommendations. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer's disease: A systematic review. [2023]