Disease-Modifying Drugs for 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: Alcohol/drug dependence, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments to determine if they can slow or improve Alzheimer's disease symptoms. The study tests several drugs, including E2814 (an experimental treatment), Gantenerumab, Lecanemab, and Solanezumab, to assess their impact on memory, thinking, and disease markers in the body. Suitable participants have a family history of Alzheimer's with a known genetic mutation and are beginning to experience early memory issues or have mild dementia. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for effective new therapies.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain anticoagulants (blood thinners) except low-dose aspirin. It's best to discuss your specific medications with the trial team.

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

A previous study found lecanemab to be generally well-tolerated over four years. Some patients experienced side effects like headaches and injection site reactions, but these were not severe for most. Gantenerumab underwent long-term safety testing and did not cause major health problems for many patients, though some experienced mild to moderate side effects, such as swelling or changes in the brain seen on MRI scans. Research has shown solanezumab to be safe, with only minor side effects like nausea and dizziness reported. E2814 is still under study, so detailed safety information remains unclear. However, its inclusion in an advanced trial indicates that earlier tests did not raise major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Alzheimer's disease because they target the underlying causes of the disease rather than just its symptoms. Unlike current standard treatments like cholinesterase inhibitors and NMDA receptor antagonists, E2814 and lecanemab aim to modify disease progression by targeting amyloid-beta and tau proteins, which are believed to play key roles in Alzheimer's disease. Lecanemab, for instance, helps clear amyloid plaques from the brain, potentially slowing cognitive decline. E2814 focuses on inhibiting tau propagation, which may help in maintaining brain health. These approaches represent a promising shift towards potentially altering the course of Alzheimer's disease rather than just managing its symptoms.

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

Research has shown that lecanemab, one of the treatments in this trial, appears promising for long-term management of Alzheimer's disease. It targets amyloid plaques in the brain, which are believed to contribute to the disease. Studies suggest that lecanemab may help lower amyloid levels and slow memory and thinking problems.

E2814, another treatment option in this trial, aims to reduce tau protein build-up, another factor in Alzheimer's. Although human data is limited, early signs indicate it might help slow the disease.

Gantenerumab, also included in this trial, has not improved memory and thinking skills in recent studies. While it reduces amyloid plaques, it hasn't shown significant benefits in clinical outcomes.

Solanezumab, another treatment option previously part of this trial, has shown a small improvement in memory and thinking. However, these effects are generally mild and not consistent across all studies. ^{1 2 4 6 7}

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 with or at risk of early onset Alzheimer's due to a genetic mutation. They must be able to undergo brain scans and tests, have a reliable study partner, and use effective contraception if applicable. Exclusions include significant health issues like heart disease, metal implants incompatible with MRI, recent drug/alcohol dependence, certain cancer histories, and pregnancy.

Inclusion Criteria

Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations

For women of childbearing potential, if partner is not sterilized, subject must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide)

Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion

Exclusion Criteria

Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy

I am not on blood thinners, except for low-dose aspirin.

I am not pregnant and do not plan to become pregnant during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cognitive Run-in

Cognitive, clinical, and imaging data collection to enhance study enrollment and provide baseline data

Varies

Treatment

Participants receive study drugs (e.g., E2814, lecanemab) or placebo, with some arms involving open-label administration

4 years

Regular visits for intravenous administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may receive active study drug in an open-label extension period after completing the main treatment phase

Varies

What Are the Treatments Tested in This Trial?

Interventions

• E2814
• Gantenerumab
• Lecanemab
• Solanezumab

Trial Overview The trial is testing the safety and effectiveness of drugs Gantenerumab, Solanezumab, E2814, Lecanemab against placebos in slowing cognitive decline or improving biomarkers in Alzheimer's patients. Participants will receive either one of the drugs or a placebo while researchers track their cognitive health over time.

How Is the Trial Designed?

Group I: Solanezumab Experimental Treatment 1 Intervention

This arm completed and is closed.

Group II: Matching placebo (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 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.

Group III: Gantenerumab Experimental Treatment 1 Intervention

This arm completed and is closed.

Group IV: 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 V: Cognitive Run-in Active Control 1 Intervention

This arm is completed and closed.

Group VI: Gantenerumab Open Label Extension Active Control 1 Intervention

Subcutaneously every 4 weeks at escalating doses. This arm is completed and closed.

Group VII: Matching Placebo (Solanezumab) Placebo Group 1 Intervention

This arm completed and is closed.

Group VIII: Matching placebo (Gantenerumab) Placebo Group 1 Intervention

This arm completed and is closed.

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+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Avid Radiopharmaceuticals

Industry Sponsor

Trials

66

Recruited

9,700+

Dr. Daniel M. Skovronsky

Avid Radiopharmaceuticals

Chief Executive Officer since 2004

MD and PhD in Neuroscience from the University of Pennsylvania

Dr. Adam S. Fleisher

Avid Radiopharmaceuticals

Chief Medical Officer since 2022

MD, MAS

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

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Accelerating Medicines Partnership (AMP)

Collaborator

Trials

3

Recruited

880+

Published Research Related to This Trial

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]

Gantenerumab, a fully human anti-β-amyloid monoclonal antibody, has shown promise in reducing brain Aβ deposition in a 6-month PET study involving 16 Alzheimer's disease patients, potentially enhancing the brain's ability to clear amyloid through microglial activity.

Ongoing Phase III trials of gantenerumab aim to assess whether the observed reduction in Aβ levels can lead to meaningful clinical benefits in patients with mild dementia and in presymptomatic individuals with genetic risk for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety studies of gantenerumab in patients with Alzheimer's disease. Panza, F., Solfrizzi, V., Imbimbo, BP., et al.[2019]

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 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]

A systematic review of 40 Phase 2 and Phase 3 clinical trials on anti-amyloid and anti-tau therapies for Alzheimer's disease revealed that lecanemab, donanemab, and aducanumab are the most advanced treatments, showing efficacy in reducing amyloid and tau proteins in the brain.

These therapies are primarily focused on passive immunotherapy targeting amyloid plaques, and their effectiveness raises important considerations for patient selection based on genetic factors like the APOE4 allele, suggesting a need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion. Esquer, A., Blanc, F., Collongues, N.[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]

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]

Citations

1. eisai.com eisai.com/news/2025/news202548.html

Eisai To Present Four-Year Efficacy And Safety Data On ... “The data presented at AAIC 2025 will highlight long-term findings from lecanemab's open-label extension trial, real-world lecanemab case ...

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

Examining Phase III potential in Alzheimer's therapeutics - PMC The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease‐ ...

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

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

4. eisai.com eisai.com/news/2025/pdf/enews202548pdf.pdf

July 22, 2025 Latest findings from Eisai's robust Alzheimer's disease (AD) pipeline include results from lecanemab long- term data, an immunoassay for ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01760005

NCT01760005 | Dominantly Inherited Alzheimer Network ... The purpose of this study is to assess the safety, tolerability, biomarker, cognitive and clinical efficacy of investigational products in participants with an ...

7. ctv.veeva.com ctv.veeva.com/study/a-study-of-e2814-with-concurrent-lecanemab-treatment-in-participants-with-early-alzheimers-disease

A Study of E2814 With Concurrent Lecanemab Treatment in ... 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 ...