LY3540378 for Chronic Heart Failure

No longer recruiting at 202 trial locations

Overseen By Seth J. Baum

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Low LVEF, Recent cardiac surgery, Cardiomyopathy, Chronic lung disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test LY3540378, a new treatment for people with worsening heart failure who have a preserved ejection fraction (a measure of how well the heart pumps blood). The study will evaluate the effectiveness and safety of this treatment compared to a placebo. Participants will receive one of three different doses of LY3540378 or a placebo to assess their response. The trial seeks individuals who have recently required hospital treatment for heart failure and exhibit symptoms like shortness of breath or leg swelling. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that LY3540378, a long-acting version of the hormone relaxin, is being tested for treating chronic heart failure. Studies have found that LY3540378 remains in the body longer, potentially allowing for less frequent dosing. Earlier research also demonstrated that LY3540378 improved blood flow to the kidneys, which is crucial because better kidney function can aid in managing heart failure.

Regarding safety, early results suggest that LY3540378 is generally well-tolerated. Although specific side effects are not listed, its progression to this stage of testing indicates a reasonable safety profile so far. However, as with any treatment, individual experiences may vary, and potential participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic heart failure, which typically include medications like ACE inhibitors, beta-blockers, and diuretics, LY3540378 offers a fresh approach. Researchers are excited because LY3540378 is administered subcutaneously, meaning it is injected under the skin, which could offer more consistent absorption and potentially fewer side effects. This treatment also represents a novel mechanism of action, targeting pathways that current medications do not, which could lead to improved heart function and better outcomes for patients. Its innovative delivery and action have the potential to change how chronic heart failure is managed.

What evidence suggests that LY3540378 could be an effective treatment for heart failure?

Research has shown that LY3540378, a drug similar to relaxin, might help treat chronic heart failure. Studies have found that it improves blood flow to the kidneys, which is crucial since heart failure often impairs kidney function. This improvement could lead to better health outcomes for heart failure patients. Additionally, LY3540378 remains active in the body for an extended period, potentially offering lasting benefits. Early results suggest it could support both heart and kidney health, making it a promising option for individuals with worsening heart failure. Participants in this trial will receive one of three different doses of LY3540378 or a placebo to evaluate its effectiveness and safety. ^{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 chronic heart failure who've had a recent worsening event requiring intravenous diuretics. They must have had a preserved ejection fraction (≥50%) documented within the last year and been on loop diuretics for at least 30 days prior to their worsening event. Exclusions include recent acute coronary events, uncorrected thyroid disease, certain cardiomyopathies, severe lung diseases like COPD, or planned heart surgeries.

Inclusion Criteria

I was hospitalized or had an urgent visit for heart failure and treated with IV diuretics recently.

I have been on a water pill for heart or kidney issues for at least 30 days.

My heart's pumping ability is confirmed to be good.

Exclusion Criteria

I have or will have a heart assist device or heart transplant.

I have a diagnosed heart muscle condition.

I've had recent major heart surgery or plan to have one during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3540378 or placebo subcutaneously

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3540378
• Placebo

Trial Overview The study tests LY3540378's effectiveness and safety against a placebo in improving conditions for those with worsening chronic heart failure but preserved ejection fraction. Participants will be randomly assigned to receive either the investigational drug or an inactive substance without knowing which one they're getting.

How Is the Trial Designed?

Group I: LY3540378 Dose 3 Experimental Treatment 1 Intervention

Participants will receive LY3540378 SC.

Group II: LY3540378 Dose 2 Experimental Treatment 1 Intervention

Participants will receive LY3540378 SC.

Group III: LY3540378 Dose 1 Experimental Treatment 1 Intervention

Participants will receive LY3540378 subcutaneously (SC).

Group IV: Placebo Placebo Group 1 Intervention

Participants will be given placebo 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

Over the past 30 years, heart failure management has significantly improved, particularly for patients with heart failure and reduced ejection fraction (HFrEF), leading to better quality of life and outcomes.

Ongoing trials are exploring both established and new pharmacological treatments that could enhance therapy for HFrEF and potentially benefit patients with heart failure with preserved ejection fraction (HFpEF) and other heart failure types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New perspectives and future directions in the treatment of heart failure. Pellicori, P., Khan, MJI., Graham, FJ., et al.[2021]

In a study of 5050 patients with heart failure, vericiguat did not significantly improve health status outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) compared to placebo, indicating it may not enhance quality of life despite its use.

However, vericiguat effectively reduced the risk of cardiovascular death or heart failure hospitalization across different baseline health statuses, suggesting it is beneficial for clinical outcomes in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat and Health-Related Quality of Life in Patients With Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial. Butler, J., Stebbins, A., Melenovský, V., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05592275

NCT05592275 | A Study of LY3540378 in Participants With ... The main purpose of this study is to assess the efficacy and safety of LY3540378 in adults with worsening heart failure with preserved ejection fraction.

2. nature.com nature.com/articles/s41591-025-03939-6

Effects of volenrelaxin in worsening heart failure with ... et al. Development of a long-acting relaxin analogue, LY3540378, for treatment of chronic heart failure. Br. J. Pharmacol. 180, 1965–1980 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38782726/

Volenrelaxin (LY3540378) increases renal plasma flow Results: Volenrelaxin demonstrated an extended half-life and increased acute and chronic ... chronic kidney disease and chronic heart failure.

4. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16055

Development of a long‐acting relaxin analogue, LY3540378 ... Here, we present the development of a long-acting relaxin analogue to be tested in the treatment of chronic heart failure. Experimental Approach.

5. academic.oup.com academic.oup.com/ndt/article/40/1/109/7680605

Volenrelaxin (LY3540378) increases renal plasma flow et al. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis . Eur Heart J. 2014.