Efficacy and Safety of Human Neuregulin-1 to Treat Stable Chronic Heart Failure (ZS-01-210)

A Randomized, Parallel, Placebo-controlled, Double-blind Phase IIa Study of Efficacy and Safety of Recombinant Human Neuregulin-1 (Neucardin) in Subjects With Stable Chronic Heart Failure

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.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: rhNRG-1 Dose 1; Drug: rhNRG-1 Dose 2

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 Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego
    • Los Angeles, California, United States, 90033
      • Metabolic Clinic and Research Center
    • Los Angeles, California, United States, 90033
      • USC Cardiovascular Division
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular & Interventional Consultants, MD, PA
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Louisiana
    • Kenner, Louisiana, United States, 70065
      • MedPharmics, LLC.
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research
  • Texas
    • Houston, Texas, United States, 77002
      • East Texas Cardiology
    • Plano, Texas, United States, 75075
      • The Medical Center of Plano
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subcutaneous administration for daily for 8 hours a day for 10 days	Drug: Placebo; Daily subcutaneous administration for 8 hours a day for 10 days; Other Names: Placebo: 0 dose
Experimental: rhNRG-1 Dose 1; Subcutaneous administration for daily for 8 hours a day for 10 days	Drug: rhNRG-1 Dose 1; Daily subcutaneous administration for 8 hours a day for 10 days; Other Names: Neucardin
Experimental: rhNRG-1 Dose 2; Subcutaneous administration for 8 hours a day for 10 days	Drug: rhNRG-1 Dose 2; Daily subcutaneous administration for 8 hours a day for 10 days; Other Names: Neucardin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in LVEF	Compared to baseline and placebo	30 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.
• Collaborators: Zensun USA Inc.
• Investigators: Study Chair: Barry Greenberg, MD, University of California, San Diego; Principal Investigator: Uri Elkayam, MD, LAC+USC Medical Center

Publications and helpful links

General Publications

• Xu Y, Li X, Liu X, Zhou M. Neuregulin-1/ErbB signaling and chronic heart failure. Adv Pharmacol. 2010;59:31-51. doi: 10.1016/S1054-3589(10)59002-1.
• Jabbour A, Hayward CS, Keogh AM, Kotlyar E, McCrohon JA, England JF, Amor R, Liu X, Li XY, Zhou MD, Graham RM, Macdonald PS. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail. 2011 Jan;13(1):83-92. doi: 10.1093/eurjhf/hfq152. Epub 2010 Sep 1.
• Gao R, Zhang J, Cheng L, Wu X, Dong W, Yang X, Li T, Liu X, Xu Y, Li X, Zhou M. A Phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. J Am Coll Cardiol. 2010 May 4;55(18):1907-14. doi: 10.1016/j.jacc.2009.12.044.
• Liu X, Gu X, Li Z, Li X, Li H, Chang J, Chen P, Jin J, Xi B, Chen D, Lai D, Graham RM, Zhou M. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. J Am Coll Cardiol. 2006 Oct 3;48(7):1438-47. doi: 10.1016/j.jacc.2006.05.057. Epub 2006 Sep 14.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 30, 2010
• First Posted (Estimate): December 1, 2010

Study Record Updates

• Last Update Posted (Actual): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Heart Failure; Stable; Systolic
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ZS-01-210