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

(DIAN-TU Trial)

Not currently recruiting at 47 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, E2814 (an experimental treatment) and lecanemab, to determine if they can slow early-onset Alzheimer's disease. The goal is to assess whether these drugs can improve brain health markers and reduce the progression of memory and thinking problems. Participants will receive either the drugs or a placebo for comparison. Eligible participants include those with a known genetic mutation causing Alzheimer's and who are experiencing early symptoms or mild memory issues. As a Phase 2/3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking Alzheimer's treatments.

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.

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

Research has shown that E2814 has been studied for its safety and tolerability in people with certain types of Alzheimer's. Studies suggest it might help prevent tau proteins from accumulating in the brain, potentially slowing the disease. While this is promising, researchers continue to collect more specific safety information.

Lecanemab has undergone more extensive testing and has been well-tolerated in several studies. However, some risks exist, such as changes in brain scans, which doctors monitor closely. Long-term use has not revealed any new safety concerns.

Both treatments are under further study to better understand their safety. Prospective trial participants should discuss these details with the trial coordinators. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard Alzheimer's treatments that mainly focus on managing symptoms, E2814 and lecanemab are designed to target the underlying disease process. E2814 is unique because it aims to inhibit tau propagation, a protein associated with neurodegeneration, potentially slowing disease progression. Lecanemab, on the other hand, works by targeting amyloid-beta plaques, which are believed to play a crucial role in Alzheimer's development. Researchers are excited about these treatments because they offer a dual approach that targets both tau and amyloid-beta, potentially providing a more comprehensive treatment strategy for early-onset Alzheimer's disease.

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

Research has shown that E2814, an investigational drug in this trial, may help treat Alzheimer's by stopping the spread of harmful proteins in the brain. Studies have found that E2814 can reduce clumps of these proteins and lower levels of a specific marker, p-tau217, linked to Alzheimer's progression. Meanwhile, lecanemab, another treatment option in this trial, reduced amyloid protein and slowed memory and thinking problems after three years of treatment. Together, these treatments target different aspects of Alzheimer's, offering hope for slowing the disease in people with early onset. ^{1 4 6 7 8}

Who Is on the Research Team?

Randall J Bateman, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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 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 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]

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 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, 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]

Citations

1. eisai.com eisai.com/news/2024/news202480.html

EISAI PRESENTS LATEST CLINICAL FINDINGS ... These results suggest that E2814 inhibited tau propagation and suppressed the accumulation of tau aggregates in brains of people living with DIAD.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12360189/

An Anti-tau Therapeutic Antibody Etalanetug (E2814) The results of this study help to confirm the potential of etalanetug, an anti-tau mAb, to inhibit the propagation of pathologic tau species by ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05269394

NCT05269394 | Dominantly Inherited Alzheimer Network ... A study of potential disease modifying treatments in individuals with a type of early onset Alzheimer's disease caused by a genetic mutation.

4. media-us.eisai.com media-us.eisai.com/2024-10-30-EISAI-PRESENTS-LATEST-CLINICAL-FINDINGS-SUGGESTING-INHIBITION-OF-TAU-PROPAGATION-BY-ANTI-MTBR-TAU-ANTIBODY-E2814-AT-THE-17TH-CLINICAL-TRIALS-ON-ALZHEIMERS-DISEASE-CONFERENCE-CTAD

Eisai presented findings on anti-MTBR tau antibody E2814 at ... These results suggest that E2814 inhibited tau propagation and suppressed the accumulation of tau aggregates in brains of people living with DIAD.

5. neurologylive.com neurologylive.com/view/anti-tau-agent-e2814-impact-early-late-tau-biomarkers-further-supporting-development

Anti-Tau Agent E2814 Shows Impact on Early and Late ... Despite a small cohort sample size, treated patients with E2814 demonstrated significant reductions in p-tau217 after 12 weeks of treatment, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04971733

A Study to Assess Safety and Target Engagement of E2814 ... The primary objective of the study is to assess the safety and tolerability of intravenous (IV) infusions of E2814 in participants with dominantly inherited ...

7. media-us.eisai.com media-us.eisai.com/2025-07-21-EISAI-TO-PRESENT-FOUR-YEAR-EFFICACY-AND-SAFETY-DATA-ON-CONTINUOUS-TREATMENT-WITH-LECANEMAB-AT-THE-ALZHEIMERS-ASSOCIATION-INTERNATIONAL-CONFERENCE-2025

Eisai to Present Four-Year Efficacy and Safety Data on ... A Featured Research Session on Wednesday, July 30 (4:15 – 5:45 PM EDT) will include findings from the Anti-Tau Etalanetug (E2814) with Lecanemab ...

8. prnewswire.com prnewswire.com/news-releases/eisai-to-present-four-year-efficacy-and-safety-data-on-continuous-treatment-with-lecanemab-at-the-alzheimers-association-international-conference-2025-302509714.html

Eisai to Present Four-Year Efficacy and Safety Data on ... A Featured Research Session on Wednesday, July 30 (4:15 – 5:45 PM EDT) will include findings from the Anti-Tau Etalanetug (E2814) with Lecanemab ...