Study to Evaluate Effects of INL1 in Patients With Heart Failure and Reduced Ejection Fraction (TRACER-HF)

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of INL1 in Patients With Heart Failure and Reduced Ejection Fraction

This is a multicenter, randomized, double-blind, placebo-controlled, dose-response trial in patients with chronic stable Heart Failure (HF) and reduced Left Ventricular Ejection Fraction (LVEF) to evaluate the efficacy and safety of three INL1 doses compared with placebo. Patients will be treated for approximately 12 weeks with one of three INL1 doses: 50 mg, 150 mg, 300 mg, or, placebo capsules, taken twice daily (BID).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Reduced Ejection Fraction
• Intervention / Treatment: Drug: INL1; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 862-259-4382; Email: daniel.qi@vita-spes.com

Study Locations

• China
  • Chongqing, China
    • Recruiting
    • Chongqing University 3 Gorges Hospital
    • Contact: Lirong Qui; Phone Number: 15523798618
• United States
  • California
    • Torrance, California, United States, 90502
      • Active, not recruiting
      • UCLA School of Medicine
  • Florida
    • Clearwater, Florida, United States, 33756
      • Completed
      • Innovative Research of West Florida, Inc.
    • Doral, Florida, United States, 33166
      • Withdrawn
      • Universal Axon Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Completed
      • Grady Clinical Research Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Withdrawn
      • Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Withdrawn
      • Clinical Trials of America LA, LLC
  • Missouri
    • Saint Louis, Missouri, United States, 63136
      • Completed
      • St Louis Heart and Vascular
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Completed
      • Clinical Research of Gastonia
    • Greensboro, North Carolina, United States, 27401
      • Withdrawn
      • Medication Management, LLC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Withdrawn
      • Stern Cardiovascular
  • Texas
    • Houston, Texas, United States, 77002
      • Completed
      • East Texas Cardiology
    • Houston, Texas, United States, 77025
      • Completed
      • Angiocardiac Care of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of HF requiring chronic treatment of loop diuretics
• Left Ventricular Ejection Fraction (LVEF) ≤ 40% at screening by echocardiography
• N-Terminal-prohormone of Brain Natriuretic Peptide (NT-proBNP) ≥400 pg/mL at screening for patients without atrial fibrillation or atrial flutter, or, NT-proBNP ≥ 1,200 pg/mL at screening for patients with atrial fibrillation or atrial flutter
• Treated for Heart Failure with stable, optimal pharmacological therapy
• Acceptable screening echocardiographic image quality

Exclusion Criteria:

• Female patients of childbearing potential
• Patients with a New York Heart Association (NYHA) Class I or IV
• Heart failure that is clearly caused by toxin / drug such as Adriamycin
• Significant medical conditions or recent history suggesting the patient's study participation will potentially pose a major risk to patient's safety and well-being
• Need for routine scheduled outpatient IV infusions for Heart Failure or scheduled ultrafiltration
• History of rhabdomyolysis or history of autoimmune diseases
• Severe renal disease
• Hepatic disease
• Pulmonary disease limiting exercise capacity
• Atrial fibrillation with rapid ventricular response
• Life expectancy of less than 6 months
• Type 1 diabetes mellitus or Type 2 diabetes mellitus with very poor glycemic control
• Patients with anemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: INL1 50mg BID; INL1 50mg dose to be given twice daily using one 50mg capsule and two matching placebo capsules at each dose	Drug: INL1; Capsules
EXPERIMENTAL: INL1 150 mg BID; INL1 150mg dose to be given twice daily using three 50mg capsules at each dose	Drug: INL1; Capsules
EXPERIMENTAL: INL1 300 mg BID; INL1 300mg dose to be given twice daily using three 100mg capsules at each dose	Drug: INL1; Capsules
PLACEBO_COMPARATOR: Placebo; Placebo dose to be given twice daily using 3 placebo capsules at each dose	Other: Placebo; Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportional change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP)	Proportional change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from Baseline to 12 weeks	Baseline - 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Heart Failure (HF) Improvement Score	Composite HF Improvement Score, summarizing changes in 4 HF outcomes (NT-proBNP, left ventricular end-systolic volume [LVESV], NYHA class, and 6 Minute Walk Test) from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular End Diastolic (LVED)	Echocardiogram finding: change in LVED from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular End Systolic (LVES)	Echocardiogram finding: change in LVES from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular End Diastolic Volume (LVEDV)	Echocardiogram finding: change in LVEDV from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular End Systolic Volume (LVESV)	Echocardiogram finding: change in LVESV from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular Systolic Volume (LVSV)	Echocardiogram finding: change in LVSV from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular Ejection Fraction (LVEF)	Echocardiogram finding: change in LVEF from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular Mass (LVM)	Echocardiogram finding: change in LVM from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular End Diastolic Diameter (LVEDD)	Echocardiogram finding: change in LVEDD from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular End Systolic Diameter (LVESD)	Echocardiogram finding: change in LVESD from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Ventricular Fractional Shortening (LVFS)	Echocardiogram finding: change in LVFS from Baseline to 12 weeks	Baseline - 12 weeks
Change in ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E')	Echocardiogram finding: change in E/E' ratio from Baseline to 12 weeks	Baseline - 12 weeks
Change in Left Atrial Volume (LAV)	Echocardiogram finding: change in LAV from Baseline to 12 weeks	Baseline - 12 weeks
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE)	Echocardiogram finding: change in TAPSE from Baseline to 12 weeks	Baseline - 12 weeks
Change in Tricuspid Regurgitation (TR) peak velocity	Echocardiogram finding: change in TR peak velocity from Baseline to 12 weeks	Baseline - 12 weeks
Change in Tricuspid Regurgitation (TR) gradient	Echocardiogram finding: change in TR gradient from Baseline to 12 weeks	Baseline - 12 weeks
Change in Tricuspid Regurgitation (TR) severity	Echocardiogram finding: change in TR severity from Baseline to 12 weeks	Baseline - 12 weeks
Change in Inferior Vena Cava (IVC) Diameter	Echocardiogram finding: change IVC Diameter from Baseline to 12 weeks	Baseline - 12 weeks
Change in New York Heart Association (NYHA) class	Change in NYHA class from Baseline to 12 weeks	Baseline to 12 weeks
Change in 6 minute walk distance	Change in 6 minute walk distance from Baseline to 12 weeks	Baseline to 12 weeks
Quality of Life (QoL) based on Kansas City Cardiomyopathy Questionnaire (KCCQ) change	QoL based on change in KCCQ from Baseline to 12 weeks. Quality of Life scale can range from 0 to 100, with higher values indicating a better outcome. Change will be calculated by subtraction.	Baseline to 12 weeks
Time to earliest event among the composite of cardiovascular (CV) death, hospitalization for HF, and unplanned use of intravenous diuretics or intensification of oral diuretic dose	Time to earliest event among the composite of CV death, hospitalization for HF, and unplanned use of intravenous diuretics or intensification of oral diuretic dose from Baseline to 12 weeks	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Innolife Co., Ltd.
• Investigators: Study Chair: Michael Chen, MD, Innolife Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 20, 2020
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (ACTUAL): March 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: INL1-001; 2019-000511-89 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No