Clinical trial NCT04840914: A Study of LY3461767 in Participants With Chronic Heart Failure With Reduced Ejection Fraction
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Heart Failure With Reduced Ejection Fraction
Keywords: Heart Failure
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2021-04-12
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through Day 90
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3461767
timeFrame: Predose up to 48 hours post end of infusion
measure: PK: Maximum Concentration (Cmax) of LY3461767
timeFrame: Predose up to 48 hours post end of infusion
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina, Division of Cardiology
state: North Carolina
city: Tsuchiura
country: Japan
facility: Tsuchiura Kyodo Hospital
state: Ibaraki
city: Kanazawa Ward,Yokohama
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Cardiovascular and Respiratory Center
state: Kanagawa
city: Suita-shi
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: