Remternetug for Alzheimer's Disease

Not currently recruiting at 89 trial locations

Overseen By Jeffrey A Norton

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Anti-amyloid immunotherapy

Disqualifiers: Unstable illnesses, Cancer, Psychiatric diagnosis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new drug, remternetug, to determine if it can safely and effectively aid individuals with early symptoms of Alzheimer's disease. The study compares different methods of administering the drug, including subcutaneous shots and IV, against a placebo (a substance with no active drug). It suits those who have noticed a gradual change in their thinking abilities over the last six months and can bring a supportive friend or family member to appointments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment nearing widespread availability.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

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

Research shows that remternetug, administered either through a drip (IV) or an injection under the skin (SC), has shown promise in early studies for Alzheimer's disease. It significantly reduces amyloid plaques, which are protein clumps linked to Alzheimer's.

Safety data from earlier trials suggest that remternetug is generally well-tolerated. Some patients reported side effects, but these were usually mild to moderate. No serious safety concerns have been identified so far. Testing remternetug in a large, late-stage trial suggests that earlier safety results were encouraging.

Overall, while some side effects are possible, the treatment has been considered safe enough to advance to this stage of testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about remternetug for Alzheimer's disease because it offers a unique approach to treatment. Unlike current options such as cholinesterase inhibitors and NMDA receptor antagonists, which mainly manage symptoms, remternetug targets the disease more directly. It is an antibody that potentially modifies the disease by targeting and clearing amyloid plaques in the brain, which are believed to play a key role in Alzheimer's progression. Additionally, remternetug is available in both intravenous (IV) and subcutaneous (SC) forms, providing flexibility in how it's administered. This could make treatment more accessible and comfortable for patients, potentially improving adherence and outcomes.

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

Research has shown that remternetug might help treat early Alzheimer's disease. Studies have found that treatments like remternetug can slow the disease's progression by about 30% over 18 months. This occurs by reducing amyloid plaques in the brain, which are believed to play a role in Alzheimer's. In this trial, researchers are testing remternetug in two forms: through a drip (IV) and an injection under the skin (SC), aiming to improve memory and thinking skills. Early results suggest that remternetug could slow the worsening of symptoms, offering hope for better management of Alzheimer's. ^{1 4 5 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for individuals with early Alzheimer's who've noticed memory or cognitive decline over 6+ months. They need a reliable partner to assist with the study, must not have other neurological diseases affecting cognition, and should be able to undergo neuropsychological testing.

Inclusion Criteria

I am committed to following the study's schedule and procedures.

Do you have a friend or family member who can help you with study visits and answer questions about your health?

I have experienced a decline in memory or thinking for over 6 months.

Exclusion Criteria

You have a positive result for P-tau, which shows the presence of amyloid protein in your body.

I am a woman who cannot become pregnant.

You have a score between 20 to 28 on a test that measures your memory and thinking abilities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive remternetug or placebo via subcutaneous injection or intravenous infusion

52 weeks

Extension

Participants switch treatments; those on remternetug receive placebo and vice versa, ensuring all receive remternetug

76 weeks

Open-label Addenda

Additional participants receive open-label remternetug via subcutaneous injection or intravenous infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Remternetug (IV)
• Remternetug (SC)

Trial Overview The study tests Remternetug's safety and effectiveness in treating early Alzheimer's disease. Participants will receive either a placebo or Remternetug through subcutaneous (SC) injections or intravenous (IV) infusions.

How Is the Trial Designed?

Group I: Remternetug (SC) Experimental Treatment 1 Intervention

Participants will receive one of two dosing regimens of remternetug subcutaneously (SC) Participants will receive remternetug SC during the treatment period, then switch to placebo SC in the extension period.

Group II: Remternetug (IV) Experimental Treatment 1 Intervention

Participants will receive remternetug intravenously (IV) Participants will receive remternetug IV during the treatment period, then switch to placebo IV in the extension period.

Group III: Open-Label Addenda Remternetug (SC) Experimental Treatment 1 Intervention

Participants will receive one of nine dosing regimens of remternetug SC during the open-label addenda.

Group IV: Open-Label Addenda Remternetug (IV) Experimental Treatment 1 Intervention

Participants will receive one of six dosing regimens of remternetug IV during the open-label addenda.

Group V: Placebo Placebo Group 1 Intervention

Participants will receive placebo matching remternetug IV or SC. Participants will receive placebo IV during the treatment period, then switch to remternetug IV in the extension period. Participants will receive placebo SC during the treatment period, then switch to LY3372993 SC in the extension period.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead 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

Published Research Related to This Trial

The combination of ranimustine (MCNU) and recombinant human mutant TNF-alpha (TNF-SAM2) was found to be safe and well-tolerated in 26 patients with newly diagnosed malignant astrocytomas, with no severe or life-threatening toxicities reported.

While the treatment showed promising results in patients with anaplastic astrocytoma, leading to a median survival time of 330 weeks, it did not demonstrate improved efficacy in glioblastoma patients compared to historical controls receiving MCNU alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2) immunotherapy with ranimustine chemotherapy and concurrent radiation therapy for malignant astrocytomas. Fukushima, T., Yamamoto, M., Oshiro, S., et al.[2012]

In a study of 202 Alzheimer's disease patients who previously did not respond to donepezil or galantamine, switching to rivastigmine resulted in a 46.3% response rate after 16 weeks, indicating it can be an effective alternative treatment.

For those who did not respond to rivastigmine alone, adding memantine led to a significant 77.9% response rate, suggesting that combination therapy is both effective and safe for improving cognitive and behavioral symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer's disease who failed to benefit from previous cholinesterase inhibitor treatment. Dantoine, T., Auriacombe, S., Sarazin, M., et al.[2015]

A phase I dose-escalation study is being conducted to evaluate the safety and maximum tolerated dose of carboplatin delivered directly into the brain using convection-enhanced delivery (CED) in patients with recurrent glioblastoma multiforme (GBM), involving 18 patients divided into 6 cohorts.

Carboplatin is chosen for this method because glioblastoma cells are sensitive to it at non-toxic levels for normal brain tissue, potentially improving treatment efficacy while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of carboplatin administered by convection-enhanced delivery to patients with recurrent/progressive glioblastoma multiforme. White, E., Bienemann, A., Taylor, H., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05463731

NCT05463731 | A Study of Remternetug (LY3372993) in ... The reason for this study is to collect safety and efficacy information regarding the study drug remternetug in participants with early symptomatic Alzheimer's ...

2. neurologylive.com neurologylive.com/view/phase-3-trailrunner-alz-3-test-effects-igg1-monoclonal-antibody-remternetug-early-alzheimer-disease

Phase 3 TRAILRUNNER-ALZ 3 to Test Effects of IgG1 ... The phase 3 study will assess remternetug's efficacy in early-stage Alzheimer's, focusing on amyloid plaque reduction and cognitive outcomes.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10544555/

Clinical trials of new drugs for Alzheimer disease In the TRAILBLAZER-ALZ study, donanemab slowed disease progression by 32% at 18 months (p = 0.04 vs. placebo), thus demonstrating clinical efficacy [51].

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06653153

A Study of Remternetug (LY3372993) in Early Alzheimer's ... The purpose of this study is to measure the difference in time to developing or worsening memory, thinking, or functional problems due to Alzheimer's disease.

5. clinicaltrialsarena.com clinicaltrialsarena.com/features/trials-to-watch-three-major-catalysts-in-alzheimers-disease/

Trials to watch: Three major catalysts in Alzheimer's disease Eli Lilly is looking to build on the success of Kisunla with a second amyloid targeting drug, remternetug. A monoclonal antibody (mAb), ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06647498

NCT06647498 | A Study of a Potential Disease Modifying ... The purpose of this research study is to test the study drug, referred to as remternetug, to determine its effectiveness for the study treatment of ...

7. neurologylive.com neurologylive.com/view/eli-lilly-remternetug-demonstrates-significant-amyloid-plaque-removal-early-stage-trial

Eli Lilly's Remternetug Demonstrates Significant Amyloid ... Safety and amyloid plaque reduction effects of remternetug in patients with Alzheimer's disease: interim analysis from a phase 1 study.