LY3372993 for Alzheimer's Disease

No longer recruiting at 18 trial locations

Overseen By Gene W Voskuhl

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must not be taking: Biologics, Herbal medications

Disqualifiers: Asthma, Autoimmune disease, Cardiovascular, others

Compensation: Varies

Number of Visits: 62

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment called LY3372993 for Alzheimer's disease (AD). Researchers aim to determine how the treatment affects the body and how much enters the bloodstream. The trial has two parts: one for individuals with AD and another for healthy individuals of first-generation Japanese origin. Those who have noticed memory problems for at least six months or are healthy and of full Japanese descent might be eligible to join. Participants may need to visit the study center up to 31 times over approximately 61 weeks. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

For healthy participants in Part B, you must stop using any over-the-counter or prescription medications, including herbal ones, 14 days before starting the trial. The protocol does not specify medication restrictions for participants with Alzheimer's in Part A.

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

Research shows that LY3372993, also known as remternetug, is under evaluation for safety in treating Alzheimer's disease. In earlier studies, most participants tolerated the treatment well. Some side effects occurred, but they were usually mild to moderate. Detailed safety information from these studies indicates that serious side effects were rare. This offers a positive view of LY3372993's safety for potential trial participants. However, this is based on past studies, and individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about LY3372993 for Alzheimer's disease because it offers a fresh approach compared to existing treatments, which mainly focus on managing symptoms rather than altering disease progression. Unlike current drugs, LY3372993 is administered either intravenously or subcutaneously and is being explored for its potential to target underlying disease mechanisms. This targeted action could mean more effective management of Alzheimer's symptoms and, hopefully, a slowing or altering of the disease's progression, sparking hope for better outcomes in patients.

What evidence suggests that LY3372993 might be an effective treatment for Alzheimer's Disease?

Research has shown that LY3372993, also known as remternetug, may help treat Alzheimer's disease by reducing amyloid plaques in the brain. These plaques, clumps of protein, can harm brain cells and are believed to contribute to Alzheimer's. In one study, 75% of participants experienced a significant reduction in amyloid plaques after receiving LY3372993. Another study found that LY3372993 might slow the worsening of Alzheimer's symptoms, such as memory and thinking problems. These early results suggest that LY3372993 could be a promising treatment for Alzheimer's disease. Participants in this trial will receive either LY3372993 or a placebo to further evaluate its effectiveness. ^{1 6 7 8 9}

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 adults with Alzheimer's Disease (AD) showing memory decline for over 6 months and healthy individuals, including those of first-generation Japanese origin. AD participants need a partner to assist during the study. Healthy subjects must be within certain body weight limits and not on recent medications.

Inclusion Criteria

(Part A) Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available through telephone at designated times

If you want to take part in the study, you and your family must have Japanese heritage, and all your grandparents must have been born in Japan.

I am generally in good health.

Exclusion Criteria

I have had serious dizziness or fainting episodes in the last 3 years.

(Part B) You have any important heart or brain scan irregularities.

I haven't taken any biologic drugs like monoclonal antibodies in the last 3 months or 5 half-lives, whichever is longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Part A)

Participants with Alzheimer's Disease receive multiple doses of LY3372993 or placebo either intravenously (IV) or subcutaneously (SC)

61 weeks

Up to 31 visits to the study center

Treatment (Part B)

Healthy participants receive a single dose of LY3372993 or placebo either intravenously (IV) or subcutaneously (SC)

13 weeks

Up to 31 visits to the study center

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3372993
• Placebo

Trial Overview The safety and effects of LY3372993 are being tested in two parts: one with Alzheimer's patients and another with healthy people, possibly including first-generation Japanese individuals. The study will measure how much drug gets into the blood and its impact on participants.

How Is the Trial Designed?

Group I: LY3372993 (Part B) Experimental Treatment 1 Intervention

LY3372993 administered as single dose IV or SC.

Group II: LY3372993 (Part A) Experimental Treatment 1 Intervention

LY3372993 administered as multiple doses either intravenously (IV) or subcutaneously (SC).

Group III: Placebo (Part A) Placebo Group 1 Intervention

Placebo administered as multiple doses IV or SC.

Group IV: Placebo (Part B) Placebo Group 1 Intervention

Placebo administered as single dose IV or SC.

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

Predictive models can effectively identify individuals with Alzheimer's disease who are unlikely to show cognitive decline, which can enhance the selection process for clinical trials.

In a study involving data from two phase 3 trials with 18 months of follow-up, nearly half of the placebo-treated patients showed no cognitive decline, indicating that using these models could improve the power of trials by focusing on participants expected to decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of predictive models in boosting power of Alzheimer's disease clinical trials: A post hoc analysis of phase 3 solanezumab trials. Ezzati, A., Davatzikos, C., Wolk, DA., et al.[2023]

In an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

In a study involving 144 subjects with amnestic mild cognitive impairment, AL-108 was found to be generally safe and well tolerated over 12 weeks of treatment.

While the overall efficacy analysis did not show a significant difference in cognitive memory scores between AL-108 and placebo, there were promising signals of potential efficacy in specific memory and attention tasks, suggesting further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Morimoto, BH., Schmechel, D., Hirman, J., et al.[2016]

In a review of 23 randomized, placebo-controlled trials for Alzheimer's disease lasting 18 months, no trial demonstrated statistically significant benefits for the test drug, highlighting challenges in detecting modest drug efficacy in this timeframe.

The placebo groups showed a consistent decline in cognitive function (measured by the ADAS-cog) over 18 months, with variability in outcomes suggesting that many patients do not experience significant worsening, complicating the ability to identify effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Alzheimer's disease clinical trials: methods and placebo outcomes. Schneider, LS., Sano, M.[2022]

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. 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].

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

Eli Lilly's Remternetug Demonstrates Significant Amyloid ... Amyloid clearance was achieved by 75% of participants who received remternetug at doses ranging from 700 to 2800 mg IV Q4Q by day 169.

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. trial.medpath.com trial.medpath.com/clinical-trial/3684eb060bb6d254/nct06653153-remternetug-versus-placebo-alzheimers-disease

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 ...

6. trials.lilly.com trials.lilly.com/en-US/trial/351135

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

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04451408

NCT04451408 | A Study of LY3372993 in Participants With ... The main purpose of this study is to evaluate the safety and tolerability of LY3372993 in participants with AD, non-Japanese, and Japanese healthy participants.

8. sciencedirect.com sciencedirect.com/science/article/pii/S003537872200738X

High-clearance anti-amyloid immunotherapies in ... Here, we review the available evidence regarding efficacy and safety data and medico-economical aspects for high-clearance anti-amyloid immunotherapies.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10789674/

Anti-Amyloid Monoclonal Antibodies for the Treatment of ... Two monoclonal antibodies (mAbs), aducanumab and lecanemab, have received accelerated approval from the US FDA for initiation of treatment in early Alzheimer's ...