LY3372993 for Alzheimer's Disease

Recruiting at 17 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

139 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called LY3372993 to see if it is safe and how well people can tolerate it. The study includes people with Alzheimer's Disease and healthy individuals, both non-Japanese and first-generation Japanese. Researchers will measure how much of the drug gets into the bloodstream and observe its effects on the body.

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.

How is the drug LY3372993 different from other Alzheimer's treatments?

LY3372993 is unique because it is being tested as a potential treatment for Alzheimer's disease, which currently has no cure. Unlike other treatments, it may work by targeting specific brain receptors to improve cognitive function, although its exact mechanism is still under investigation. ^{1 2 3 4 5}

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

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]

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

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies. [2021]

3. United States 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. [2023]

4. Switzerland 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. [2016]

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

Current Alzheimer's disease clinical trials: methods and placebo outcomes. [2022]