Efficacy and Safety of Human Neuregulin-1 to Treat Stable Chronic Heart Failure

Phase 2

Completed

• Conditions: Chronic Heart Failure
• Interventions: Drug: Placebo; Drug: rhNRG-1 Dose 1; Drug: rhNRG-1 Dose 2

• Registration Number: NCT01251406
• Lead Sponsor: Zensun Sci. & Tech. Co., Ltd.

Brief Summary

The mortality of chronic heart failure patients remains high. Recombinant human Neuregulin-1 (rhNRG-1, also called Neucardin) is a 61 amino acid peptide that acts directly on damaged heart muscle cells to restore their structure and function. This study will investigate the safety and efficacy of rhNRG-1 to treat stable chronic heart failure.

Detailed Description

This randomized, parallel, placebo-controlled, double-blind, multi-center study will assess the safety and efficacy of rhNRG-1 also known as Neucardin as a treatment for stable chronic heart failure.

A total of 120 subjects, who have chronic heart failure with a NYHA classification of II or III, and are on a stable regimen of ACEI/angiotensin receptor blocker (ARB), beta-blocker, and/or diuretic for at least 3 months prior to receiving study medication and anticipated to remain on the stable regimen through the treatment period can enroll as per specific inclusion and exclusion criteria.

Subjects will be hospitalized for 10 days during the treatment period and will be infused subcutaneously with rhNRG-1 or placebo.

Study Timeline

• Study First Submitted: 2010-11-17
• Study First Submitted QC: 2010-11-30
• Study First Posted: 2010-12-01
• Study Start: 2012-01
• Primary Completion: 2012-12
• Study Completion: 2014-03
• Disposition First Posted: 2021-04-26
• Status Verified: 2025-01
• Disposition First Submitted: 2025-01-23
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67

Inclusion Criteria

• Age > 18 years.
• Male or female subjects.
• Have chronic heart failure defined as NYHA classification of II or III.
• Be on a stable regimen of ACEI/ARB and/or beta-blocker 3 months prior to receiving study medication and are expected to remain on a stable HF medication regime throughout the duration of the trial.
• Left ventricular ejection fraction (LVEF) of < 35% as determined at screening by 2-D echocardiography.
• Is able to understand and provide informed consent.
• If subject has dilated cardiomyopathy, ischemic heart disease or corrected valvular heart disease, and had surgery to repair or replace value, the surgery must have been performed 3 months prior to receiving study medication and the surgical area is functioning normally.
• Proper birth control must be used at least 3 weeks prior to the study (women only), during the infusion period of study drug (men and women), 4-weeks after study drug administration (men and women) and the remaining 11 months in the study follow-up (women). Women must have a negative pregnancy test at screening.
• No greater than mild pericardial effusion < 0.5 cm on echocardiography (roughly corresponds to < 100 mL).
• Have an implantable cardioverter-defibrillator (ICD). The ICD should have been implanted at least 3 months prior to receiving study medication. Patients should undergo interrogation of their ICDs between 1 and 7 days before randomization to drug for the previous thirty (30) days. This interrogation would include surveillance for ventricular arrhythmias as well as assessment of ICD discharge(s) and/or anti-tachycardia pacing.

Exclusion Criteria

• Has chronic heart failure classified as NYHA Class I or IV.
• Has a history of any malignancy or positive test as specified in the pre-cancer screening.
• Have other conditions which in the opinion of the investigator preclude participation in the study, e.g. serious co-morbidity, known or suspected substance abuse or non-compliance.
• Has a body weight >350lbs.
• Has had any cause hospitalization 30 days prior to screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subcutaneous administration for daily for 8 hours a day for 10 days
rhNRG-1 Dose 1	rhNRG-1 Dose 1	Subcutaneous administration for daily for 8 hours a day for 10 days
rhNRG-1 Dose 2	rhNRG-1 Dose 2	Subcutaneous administration for 8 hours a day for 10 days

Primary Outcome Measures

Name	Time	Method
Change from baseline in LVEF	30 days	Compared to baseline and placebo

Secondary Outcome Measures

Name	Time	Method
NYHA class status	Day 30, 90, 180 and 365	Compared to baseline and placebo
All cause mortality and all cause hospitalization	Days 30, 90, 180 and 365	Compared to baseline and placebo
Six (6) minute walk test	Day 30, 90, 180, 365	Compared to baseline and placebo
Quality of Life Questionnaire (Kansas City Cardiomyopathy Questionnaire)	Day 30, 90, 180 and 365	Compared to baseline and placebo
Change in LVESV and LVEDV	Day 30	Compared to baseline and placebo

Trial Locations

Locations (13)

University of California, San Diego; 🇺🇸 La Jolla, California, United States

Metabolic Clinic and Research Center; 🇺🇸 Los Angeles, California, United States

USC Cardiovascular Division; 🇺🇸 Los Angeles, California, United States

Orange County Research Center; 🇺🇸 Tustin, California, United States

Clearwater Cardiovascular & Interventional Consultants, MD, PA; 🇺🇸 Clearwater, Florida, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

MedPharmics, LLC.; 🇺🇸 Kenner, Louisiana, United States

Benchmark Research; 🇺🇸 Metairie, Louisiana, United States

East Texas Cardiology; 🇺🇸 Houston, Texas, United States

The Medical Center of Plano; 🇺🇸 Plano, Texas, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

University of Colorado Denver; 🇺🇸 Denver, Colorado, United States

Sentara Cardiovascular Research Institute; 🇺🇸 Norfolk, Virginia, United States