A Study of LY3461767 in Participants With Chronic Heart Failure With Reduced Ejection Fraction

Study Overview
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Brief Summary
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The main purpose of this study is to determine the tolerability and safety of LY3461767 with any side effects that might be associated with it. Study drug will be provided in a continuous subcutaneous infusion lasting 24 hours to 96 hours, depending on the cohort. Blood tests will be performed to check concentrations of LY3461767 in the bloodstream and how long it takes the body to get rid of it in participants with chronic heart failure with reduced ejection fraction (HFrEF). The study will last up to 3 months and may include 5 visits.

Official Title
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A Single-Dose Study Evaluating Different Dose Levels and Subcutaneous Infusion Durations on Safety, Pharmacokinetics, and Pharmacodynamics of LY3461767 in Participants With Chronic Heart Failure With Reduced Ejection Fraction

Conditions
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Chronic Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Drug: LY3461767
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are males and in agreement to follow contraceptive requirements, or women of non-child-bearing potential Have a body mass index (BMI) of </= 45.0 kilograms per square meter (kg/m²) Have chronic stable heart failure (New York Heart Association (NYHA) classification II and III) on guideline directed heart failure therapy for at least 6 months prior to enrolment Have not changed optimal guideline directed therapy in the last 1 month prior to screening, If treated with oral diuretics, dose must be stable for at least 2 weeks prior to screening Have Left Ventricular Ejection Fraction (LVEF) < 40% Have a record of N-terminal pro b-type natriuretic peptide (NT-ProBNP) ≥ 200 picograms per millilitre (pg/mL) or a BNP value of >/= 60 pg/mL within the past 12 months prior to screening Exclusion Criteria: Have myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke in the last 90 days prior to screening Have acute decompensated heart failure requiring IV diuretics within 12 weeks prior to screening Have cardiac amyloidosis, accumulation diseases (e.g., haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic cardiomyopathy, pericardial constriction, or complex congenital heart disease. Have any moderate-to-severe stenosis of the mitral and/or aortic valve or moderate-to severe or greater mitral and/or aortic regurgitation. Have a history or presence of hepatic, pancreatic, or biliary tract disorders Have a history of malignancy or active malignancy at screening. Have not had age-appropriate cancer screening as recommended by the American Cancer Society and per medical judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3461767<br>LY3461767 administered subcutaneously (SC). | Drug: LY3461767<br>* Administered SC.<br>|
| Placebo Comparator: Placebo<br>Placebo administered subcutaneously (SC). | Drug: Placebo<br>* Administered SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline through Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3461767 | PK: AUC of LY3461767 | Predose up to 48 hours post end of infusion | 
| PK: Maximum Concentration (Cmax) of LY3461767 | PK: Cmax of LY3461767 | Predose up to 48 hours post end of infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure