Disease-Modifying Drugs for Alzheimer's Disease

(DIAN-TU Trial)

Recruiting at36 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Monoclonal antibodies

Disqualifiers: Alcohol/drug dependence, Cardiovascular disease, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety, tolerability, biomarker, cognitive and clinical efficacy of investigational products in participants with an Alzheimer's disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive/clinical impairment or improves disease-related biomarkers.

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.

What safety data exists for lecanemab in humans?

Lecanemab has been studied for safety in people with Alzheimer's disease, and it is generally considered safe for use in patients with mild cognitive impairment or mild dementia. However, there is no safety data available for its use in earlier or later stages of the disease. ^{1 2 3 4 5}

How do the drugs E2814, Gantenerumab, Lecanemab, and Solanezumab differ from other Alzheimer's treatments?

These drugs are unique because they target amyloid-beta, a protein associated with Alzheimer's, using monoclonal antibodies (lab-made proteins that can bind to specific substances in the body). Lecanemab, for example, has shown promise in early Alzheimer's by reducing brain amyloid levels and improving cognitive function, while Gantenerumab is being studied for its potential to prevent Alzheimer's in people with genetic risk factors. ^{1 2 4 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 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.

Trial Timeline

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

Treatment Details

Interventions

• E2814 (Monoclonal Antibodies)
• Gantenerumab (Monoclonal Antibodies)
• Lecanemab (Monoclonal Antibodies)
• Solanezumab (Monoclonal Antibodies)

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.

Participant Groups

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

Group VI: Gantenerumab Open Label Extension Active Control 1 Intervention

Subcutaneously every 4 weeks at escalating doses

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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

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 Business School

Biljana Naumovic

Janssen, LP

Chief Medical Officer since 2023

MD from Belgrade University Medical School

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Dr. Joanne Pike

Alzheimer's Association

Chief Executive Officer since 2023

DrPH in Public Health Leadership from the University of North Carolina at Chapel Hill

Dr. Maria C. Carrillo

Alzheimer's Association

Chief Medical Officer

PhD in Neuroscience

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+

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]

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]

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, 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. 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]

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

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

5. New Zealand 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. [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]

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

Efficacy and safety studies of gantenerumab in patients with Alzheimer's disease. [2019]