A Study of LY3971297 in Participants With Heart Failure

NCT07547540 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: 27777J4O-MC-EZHB2026-525663-40-00
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 3

Brief Summary

The main purpose of this study is to assess how well LY3971297 is tolerated and what side effects may occur in participants with heart failure with preserved ejection fraction (HFpEF) and participants with heart failure with reduced ejection fraction (HFrEF). Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. For each participant, the study will last about 2 months and will include 1 inpatient visit lasting approximately 4 days and 5 outpatient visits.

Conditions

Heart Failure, Diastolic; Heart Failure, Systolic; Heart Failure

Outcome Measures

Primary Outcomes (2)

• Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

  Baseline through Study Completion (Approximately 2 Months)

• Number of Participants with One or More Treatment-Emergent Adverse Event

  Baseline through Study Completion (Approximately 2 Months)

Secondary Outcomes (2)

• Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3971297

  Predose on Day 1 up to Day 29 Post-Dose

• PK: Maximum Concentration (Cmax) of LY3971297

  Predose on Day 1 up to Day 29 Post-Dose

Study Arms (12)

LY3971297 Part A Cohort 1

EXPERIMENTAL

LY3971297 administered subcutaneously (SC)

Drug: LY3971297

Placebo Part A Cohort 1

PLACEBO COMPARATOR

Placebo administered SC

Drug: Placebo

LY3971297 Part A Cohort 2

EXPERIMENTAL

LY3971297 administered SC

Drug: LY3971297

Placebo Part A Cohort 2

PLACEBO COMPARATOR

Placebo administered SC

Drug: Placebo

LY3971297 Part A Cohort 3

EXPERIMENTAL

LY3971297 administered SC

Drug: LY3971297

Placebo Part A Cohort 3

PLACEBO COMPARATOR

Placebo administered SC

Drug: Placebo

LY3971297 Part A Cohort 4

EXPERIMENTAL

LY3971297 administered SC

Drug: LY3971297

Placebo Part A Cohort 4

PLACEBO COMPARATOR

Placebo administered SC

Drug: Placebo

LY3971297 Part A Cohort 5

EXPERIMENTAL

LY3971297 administered intravenously (IV)

Drug: LY3971297

Placebo Part A Cohort 5

PLACEBO COMPARATOR

Placebo administered IV

Drug: Placebo

LY3971297 Part B

EXPERIMENTAL

LY3971297 administered SC or IV

Drug: LY3971297

Placebo Part B

PLACEBO COMPARATOR

Placebo administered SC or IV

Drug: Placebo

Interventions

LY3971297 DRUG

Administered SC

LY3971297 Part A Cohort 1; LY3971297 Part A Cohort 2; LY3971297 Part A Cohort 3; LY3971297 Part A Cohort 4; LY3971297 Part B

Placebo DRUG

Administered SC

Placebo Part A Cohort 1; Placebo Part A Cohort 2; Placebo Part A Cohort 3; Placebo Part A Cohort 4; Placebo Part B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are diagnosed with chronic heart failure with New York Heart Association Class II-III (Heart Failure) HF symptomatology at screening and on guideline-directed HF therapy for at least 6 months prior to screening.
• Have not changed optimal guideline-directed HF therapy, either medication or medication dose, in the last 4 weeks prior to screening and during screening period, and do not plan to change HF therapy for the next 90 days.
• Must be on a stable dose of vasodilator therapy for at least 4 weeks prior to screening, with no dose adjustments planned during the study.
• Have an estimated glomerular filtration rate of greater than or equal to (≥) 30 milliliter per minute per 1.73 square meters (mL/Minute/1.73m²) at screening.
• Are between 30 days and within 12 months from recent heart failure hospitalization to screening.
• Have systolic blood pressure (SBP) greater than (\>) 110 millimeters of mercury (mmHg) at screening and at enrollment.
• Have a body mass index within the range of 18.5 to 40 kilograms per square meter (kg/m²) (inclusive).
• Are individuals assigned male or female at birth, who are not of childbearing potential.
• Have venous access sufficient to allow blood sampling.
• Applicable to heart failure with preserved ejection fraction (HFpEF) participants only
• Have left ventricular ejection fraction (LVEF) \>45 percent (%).
• Left atrial volume index \>34 milliliters per square meter (mL/m²) in participants in sinus rhythm, or \>40 mL/m² in participants with atrial fibrillation (AF).
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) \>300 picograms per milliliter (pg/mL) for participants without AF or \>850 pg/mL for participants with AF.
• Have a documented history of signs, symptoms, or both, consistent with HFpEF.
• Applicable to heart failure with reduced ejection fraction (HFrEF) participants only:

You may not qualify if:

• Have known allergies to related compounds of LY3971297 or any components of the formulation, or a history of significant atopy.
• Had a myocardial infarction, unstable angina pectoris, coronary artery bypass graft surgery, revascularization or other major cardiovascular surgery, stroke, or transient ischemic attack in the last 90 days prior to screening.
• Have New York Heart Association (NYHA) Class 4, acute decompensated HF (exacerbation of HF) requiring IV diuretics, IV inotropes, or IV vasodilators, within 30 days prior to screening, and/or during screening period until randomization.
• Have SBP ≥180 mmHg at screening.
• Have symptomatic hypotension.
• Have resting heart rate \>90 beats per minute (bpm) at screening.
• Have known cardiac amyloidosis, infiltrative myocardial diseases, muscular dystrophies, cardiomyopathy with reversible causes, hypertrophic cardiomyopathy, pericardial constriction, or complex congenital heart disease.
• Have any history of moderate-to-severe stenosis of the mitral and/or aortic valve or severe mitral and/or aortic regurgitation.
• Have any history of moderate-to-severe tricuspid or pulmonic valve stenosis or severe tricuspid or pulmonic regurgitation.
• Have a history of syncope that, in the opinion of the investigator, may affect the participant's safety.
• Bioprosthetic valve replacement within 12 months prior to screening or any history of mechanical valve replacement, or planned valve replacement or repair during the study period.
• Have any history of greater than moderate pulmonary hypertension.
• Have a pacemaker or implantable cardioverter-defibrillator placement within 90 days prior to screening.
• Have severe chronic obstructive pulmonary disease (COPD).
• Have clinically significant or uncontrolled cardiac arrhythmia.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

Washington University

St Louis, Missouri, 63110, United States

Location

University of North Carolina, Division of Cardiology

Chapel Hill, North Carolina, 27599, United States

Location

National Cerebral and Cardiovascular Center

Suita-shi, 564-8565, Japan

Location

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic; Heart Failure, Systolic

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Investigator is also masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2026
• First Posted: April 23, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); US (2)