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A Study of LY3540378 in Participants With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05592275
Recruitment Status : Recruiting
First Posted : October 24, 2022
Last Update Posted : April 11, 2024
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE October 20, 2022
First Posted Date  ICMJE October 24, 2022
Last Update Posted Date April 11, 2024
Actual Study Start Date  ICMJE February 3, 2023
Estimated Primary Completion Date November 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2022)
Change from Baseline in Left Atrial Reservoir Strain (LARS) [ Time Frame: Baseline, Week 26 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2023)
  • Change from Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline Left Atrial End-Systolic Volume Index (LAESVI) [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline, Week 26 ]
    eGFR calculated by creatinine and cystatin C
  • Change from Baseline in Serum Creatinine [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline in cystatin-C [ Time Frame: Baseline, Week 26 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2022)
  • Change from Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline Left Atrial End-Systolic Volume Index (LAESVI) [ Time Frame: Baseline, Week 26 ]
  • Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline, Week 26 ]
    eGFR calculated by creatinine and cystatin C
  • Change from Baseline in Serum Creatinine [ Time Frame: Baseline, Week 26 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY3540378 in Participants With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)
Official Title  ICMJE A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of LY3540378 in Adults With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Heart Failure
  • Heart Failure With Preserved Ejection Fraction
Intervention  ICMJE
  • Drug: LY3540378
    Administered SC
  • Drug: Placebo
    Administered SC
Study Arms  ICMJE
  • Experimental: LY3540378 Dose 1
    Participants will receive LY3540378 subcutaneously (SC).
    Intervention: Drug: LY3540378
  • Experimental: LY3540378 Dose 2
    Participants will receive LY3540378 SC.
    Intervention: Drug: LY3540378
  • Experimental: LY3540378 Dose 3
    Participants will receive LY3540378 SC.
    Intervention: Drug: LY3540378
  • Placebo Comparator: Placebo
    Participants will be given placebo SC.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 20, 2022)
432
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2026
Estimated Primary Completion Date November 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Prior chronic treatment, or prescription, with a loop diuretic (for example, furosemide, torsemide, bumetanide) for ≥30 days prior to the index event. Medical records, discharge notes and physician referral letters may serve as documentation for prior chronic treatment with a loop diuretic.

    • Experienced an index event, defined as a recent hospitalization for HF requiring ≥2 bolus doses of intravenous diuretics or an out- of- hospital encounter (for example, Emergency Room, clinic visit, infusion clinic, etc.) for HF requiring ≥2 bolus doses of intravenous diuretics.
    • Chronic HF diagnosed for at least 3 months before V1 (screening)
  • Documented LVEF of ≥50% within 12 months prior to screening; as measured by echocardiography, radionuclide ventriculography, invasive angiography, magnetic resonance imaging (MRI), or computerized tomograph (CT).
  • Evidence of documentation of LVEF of ≥50% may also include participant medical records, discharge notes or a referral letter from the participant's physician or referring physician that details the participant's medical history.
  • Had evidence of clinical HF syndrome consisting of

    • Hospitalization for worsening heart failure (WHF) with intravascular volume overload (the index event), as determined by the investigator, based on appropriate supportive documentation at randomization, and defined by ≥2 of the following:
    • dyspnea
    • jugular venous distention
    • pitting edema in lower extremities (>1+)
    • ascites
    • pulmonary congestion on chest X-ray
    • pulmonary rales AND participant received treatment with IV diuretics.

OR

  • Treatment for an urgent visit outside of of being hospitalized with WHF and intravascular volume overload (the index visit) requiring treatment with IV diuretics (defined as ≥2 IV doses) such as in the outpatient setting/emergency room/observation unit/infusion clinic with a clinical response within the past 2 weeks prior to randomization. Urgent visit is defined as an unplanned visit for HF defined by ≥2 of the following:

    • dyspnea
    • jugular venous distention
    • pitting edema in lower extremities (>1+)
    • ascites
    • pulmonary rales on lung examination.
  • NT-proBNP (>300 [sinus rhythm] or 900 picograms/milliliter (pg/mL) [atrial fibrillation or atrial flutter] OR brain natriuretic (BNP) (>100 [sinus rhythm] or 300 pg/mL [atrial fibrillation or atrial flutter]) at screening.

Note: The presence or absence of atrial fibrillation or atrial flutter to determine the appropriate cut-off for a given BNP or NT-proBNP sample should be evaluated using electrocardiogram (ECG) performed at screening prior to the collection of the BNP or NT-proBNP sample.

Exclusion Criteria

  • Prior documentation of low ventricle ejection fraction (LVEF) ≤45% in the past 12 months.
  • Have had acute coronary syndrome or percutaneous coronary intervention, coronary artery bypass graft, cardiac mechanical support implantation, within 3 months prior to day 2. (randomization), or any other cardiac surgery planned during the study.
  • Have had Left Ventricular assist device (LVAD) or cardiac transplantation or have cardiac transplantation planned during the study.
  • Have hypertrophic cardiomyopathy (obstructive or nonobstructive), restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac sarcoidosis, known amyloid cardiomyopathy, or inherited cardiomyopathy.
  • Have severe chronic obstructive pulmonary disease (COPD), (pulmonary arterial hypertension, etc) as defined by chronic oxygen dependence. Night-time oxygen is not exclusionary.
  • Uncorrected thyroid disease.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   Hungary,   Israel,   Japan,   Poland,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05592275
Other Study ID Numbers  ICMJE 18473
J3E-MC-EZDB ( Other Identifier: Eli Lilly and Company )
2023-505902-40-00 ( Other Identifier: EU Trial Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/
Current Responsible Party Eli Lilly and Company
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Eli Lilly and Company
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: 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) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP