What side effects are associated with this type of intervention?

The most common treatments for Alzheimer's Disease that involve anti-amyloid monoclonal antibodies, such as Aducanumab, have been associated with several side effects. These include amyloid-related imaging abnormalities (ARIA), which can manifest as brain swelling or microhemorrhages, and are reported in approximately 40% of patients treated with the highest dose of Aducanumab. Other side effects include headache, falls, diarrhea, confusion, and hypersensitivity reactions such as angioedema and urticaria. These treatments may also lead to the development of antibodies against the drug, although the clinical significance of this is not fully understood.

What prior FDA approvals exist?

The FDA has approved aducanumab, an anti-amyloid monoclonal antibody, for the treatment of Alzheimer's Disease. Aducanumab works by reducing amyloid plaques in the brain, which are believed to contribute to the progression of Alzheimer's. This approval marked a significant step as it was the first therapy targeting the underlying pathophysiology of Alzheimer's rather than just its symptoms. Other treatments for Alzheimer's have included antioxidants like vitamin E, which have shown modest benefits in delaying functional progression in patients with mild to moderate Alzheimer's Disease.

What other types of research exist?

Promising novel alternatives to Anti-Amyloid Monoclonal Antibody treatments for Alzheimer's Disease patients in 2024 include: 1) Tau protein aggregation inhibitors, which aim to prevent the formation of neurofibrillary tangles. 2) Anti-inflammatory agents targeting neuroinflammation, such as microglial modulators. 3) Synaptic function enhancers, which aim to improve synaptic plasticity and cognitive function. 4) Neuroprotective agents that aim to protect neurons from degeneration. These alternatives are being actively researched and have shown potential in clinical trials.

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Monoclonal Antibodies

Investigational Alzheimer's Drugs for Early Onset Alzheimer's Disease (DIAN-TU Trial)

Phase 2 & 3

Waitlist Available

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Individuals who know they have an Alzheimer's disease-causing mutation

Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments

Must not have

History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders

Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial

Timeline

Screening 3 weeks

Treatment Varies

Follow Up weeks 24, 52, 104, 156 and 208

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions at the injection site, headache, fatigue, allergic responses or infusion-related reactions. Side effects vary by individual; some may experience none while others could have more severe reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I can see and hear well enough to complete tests.

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I am between 18 and 80 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have significant heart, liver, kidney, infectious, immune, or hormonal diseases.

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

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ weeks 24, 52, 104, 156 and 208

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~weeks 24, 52, 104, 156 and 208

This trial's timeline: 3 weeks for screening, Varies for treatment, and weeks 24, 52, 104, 156 and 208 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The primary end point is the change from Week 24 to Week 104 and Week 208 in tau PET in the Symptomatic Population (Cohort 1).

Secondary study objectives

Asymptomatic Population (Cohort 2): Key Secondary: Change from Week 0 to Week 104 and Week 208 in CSF ptau217/total tau

Symptomatic Population (Cohort 1): Key Secondary: Change from Week 24 to Week 208 in Clinical Dementia Scale - Sum of Boxes (CDR-SB).

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: E2814 plus lecanemabExperimental Treatment2 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 lecanemabPlacebo Group2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

E2814

2019

Completed Phase 2

~80

Lecanemab

Not yet FDA approved

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Anti-amyloid monoclonal antibodies, such as those targeting amyloid-beta (Aβ) plaques, work by binding to various forms of Aβ (monomers, oligomers, plaques) and promoting their clearance from the brain. This mechanism is crucial for Alzheimer's Disease patients because the accumulation of amyloid plaques is linked to neurodegeneration and cognitive decline. By reducing these plaques, these treatments aim to slow disease progression and improve cognitive outcomes.

Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials.