LY3954068 for Alzheimer's Disease

Recruiting at 18 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must not be taking: Amyloid therapies, Anti-tau therapies

Disqualifiers: Serious illnesses, MRI contraindications, others

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LY3954068, an experimental drug, to determine its safety for individuals with early signs of Alzheimer's disease. The trial also aims to understand the drug's behavior in the body and its effects on Alzheimer's markers. Participants will receive either the treatment or a placebo through a spinal injection, once or twice, depending on the trial phase. The study seeks individuals who have experienced a gradual decline in memory for at least six months. 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?

The trial does not specify if you need to stop taking your current medications, but you cannot be on an amyloid targeted therapy (ATT) currently. If you have taken ATT in the past, it must have been more than a year ago, and this will be reviewed by the investigator.

Is there any evidence suggesting that LY3954068 is likely to be safe for humans?

Research shows that LY3954068 is being tested for safety in people with early Alzheimer's Disease. Specific information about side effects or how well people tolerate the drug is not yet available. As this is an early-stage trial, the main goal is to determine the drug's safety for humans. Detailed safety data from earlier studies is not yet available. In the trial, participants will receive one or two doses of LY3954068 directly into the spinal fluid.

Due to the trial's early stage, a complete safety profile for LY3954068 is not yet available. The study aims to learn more about the drug's effects on people and any potential side effects. Researchers will closely monitor participants to gather this important information. ^{1 2 3 4 5}

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

Researchers are excited about LY3954068 for Alzheimer's disease because it offers a fresh approach compared to existing treatments. Unlike current medications that mainly focus on symptomatic relief, LY3954068 is administered directly into the spinal fluid, targeting the brain more directly through an intrathecal (IT) method. This delivery approach could enhance the drug's effectiveness by ensuring higher concentrations reach the brain. Additionally, LY3954068's unique mechanism of action may provide benefits in slowing or modifying the progression of Alzheimer's, rather than just addressing symptoms.

What evidence suggests that LY3954068 might be an effective treatment for Alzheimer's Disease?

This trial will evaluate LY3954068 for its potential to treat Alzheimer's disease by targeting a protein called tau. Participants will receive either LY3954068 or a placebo. Research has shown that tau buildup is linked to Alzheimer's. Early findings suggest that targeting tau might slow or alter the disease's progression. Although limited information exists on LY3954068's effectiveness in humans, its approach is promising based on current understanding of tau's role in Alzheimer's. The study aims to assess how well LY3954068 manages tau proteins and its overall effects on individuals with early Alzheimer's symptoms. ^{1 3 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 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 people with early symptomatic Alzheimer's Disease. Participants will receive a single dose of LY3954068 or placebo directly into the spinal fluid. Those in Part A may join an optional part B or bridging period to another study.

Inclusion Criteria

Have gradual and progressive change in memory function for greater than or equal to (≥) 6 months as reported by the participant or informant

Have a mini mental state examination (MMSE) score of 18 to 30 at screening

Meet flortaucipir positron emission tomography (PET) criteria demonstrating evidence of tau pathology

Exclusion Criteria

Have a sensitivity to flortaucipir 18F

I do not have serious health issues that could affect the study or a life expectancy under 2 years.

I have been treated with experimental drugs or anti-tau therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single dose of LY3954068 or placebo administered intrathecally

24 weeks

Multiple visits for monitoring and assessments

Follow-up Part A

Participants are monitored for safety and effectiveness after treatment in Part A

21 weeks

Treatment Part B (Optional)

Participants receive 2 doses of LY3954068 or placebo administered intrathecally

52 weeks

Multiple visits for monitoring and assessments

Follow-up Part B (Optional)

Participants are monitored for safety and effectiveness after treatment in Part B

21 weeks

Optional Bridging Period

Participants may join an optional bridging period to a separate potential study

96 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3954068

Trial Overview The safety and blood levels of LY3954068 are being tested, along with its effects on Alzheimer's markers. The trial has two parts: Part A (single dose) and Part B (two doses), plus an optional extension into a related study.

How Is the Trial Designed?

Group I: LY3954068 (Part B) Experimental Treatment 2 Interventions

Multiple ascending dose of LY3954068 administered IT

Group II: LY3954068 (Part A) Experimental Treatment 2 Interventions

Single ascending dose of LY3954068 administered intrathecally (IT)

Group III: Placebo (Part A) Placebo Group 2 Interventions

Single ascending dose of placebo administered IT

Group IV: Placebo (Part B) Placebo Group 2 Interventions

Multiple ascending dose of placebo administered IT

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

Citations

1. trials.lilly.com trials.lilly.com/en-US/trial/466315

A First-In-Human Study of LY3954068 in Participants With ... The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD).

2. withpower.com withpower.com/trial/phase-1-alzheimer-disease-3-2024-1860c

LY3954068 for Alzheimer's Disease The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2274580725002122

CTAD taskforce: genetic therapies in Alzheimer's disease This paper will outline genetic therapy clinical trials in Alzheimer's disease and frontotemporal dementia, as well as relevant nonclinical studies.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12538647/

Tau biology, biomarkers, and therapeutics - PMC As Alzheimer's disease (AD) research advances, tau has emerged as both a critical biomarker and a promising therapeutic target, ...

5. dukeuncadrc.org dukeuncadrc.org/studies/lilly-alzheimers-disease-study

Lilly Alzheimer's Disease Study | Duke & UNC ADRC This is a Phase 1 clinical trial sponsored by Lilly, designed for individuals with mild cognitive impairment or mild Alzheimer's disease.

6. dukeuncadrc.org dukeuncadrc.org/studies/lilly

Lilly Anti-Tau siRNA Drug Active The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD).

7. synapse.patsnap.com synapse.patsnap.com/drug/41520f385b9346f99e682a057f111e8b

LY-3954068 - Drug Targets, Indications, Patents A single- and multiple-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of LY3954068 in patients with early ...

8. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/a-single-multiple-dose-study-to-evaluate-ly3954068-in-pts-with-ad/

A Single & Multiple-Dose Study to Evaluate LY3954068 in ... The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD).