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

NCT01251406 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: ZS-01-210
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 13

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.

Conditions

Chronic Heart Failure

Keywords

Stable; Chronic Heart Failure; Systolic

Outcome Measures

Primary Outcomes (1)

• Change from baseline in LVEF

  Compared to baseline and placebo

  30 days

Secondary Outcomes (5)

• Six (6) minute walk test

  Day 30, 90, 180, 365

• Quality of Life Questionnaire (Kansas City Cardiomyopathy Questionnaire)

  Day 30, 90, 180 and 365

• NYHA class status

  Day 30, 90, 180 and 365

• All cause mortality and all cause hospitalization

  Days 30, 90, 180 and 365

• Change in LVESV and LVEDV

  Day 30

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Subcutaneous administration for daily for 8 hours a day for 10 days

Drug: Placebo

rhNRG-1 Dose 1

EXPERIMENTAL

Subcutaneous administration for daily for 8 hours a day for 10 days

Drug: rhNRG-1 Dose 1

rhNRG-1 Dose 2

EXPERIMENTAL

Subcutaneous administration for 8 hours a day for 10 days

Drug: rhNRG-1 Dose 2

Interventions

Placebo DRUG

Daily subcutaneous administration for 8 hours a day for 10 days

Also known as: Placebo: 0 dose

Placebo

rhNRG-1 Dose 1 DRUG

Daily subcutaneous administration for 8 hours a day for 10 days

Also known as: Neucardin

rhNRG-1 Dose 1

rhNRG-1 Dose 2 DRUG

Daily subcutaneous administration for 8 hours a day for 10 days

Also known as: Neucardin

rhNRG-1 Dose 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zensun Sci. & Tech. Co., Ltd.: lead
• Zensun USA Inc.: collaborator

Study Sites (13)

University of California, San Diego

La Jolla, California, 92037, United States

Location

Metabolic Clinic and Research Center

Los Angeles, California, 90033, United States

Location

USC Cardiovascular Division

Los Angeles, California, 90033, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

Clearwater Cardiovascular & Interventional Consultants, MD, PA

Clearwater, Florida, 33756, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MedPharmics, LLC.

Kenner, Louisiana, 70065, United States

Location

Benchmark Research

Metairie, Louisiana, 70006, United States

Location

East Texas Cardiology

Houston, Texas, 77002, United States

Location

The Medical Center of Plano

Plano, Texas, 75075, United States

Location

Sentara Cardiovascular Research Institute

Norfolk, Virginia, 23507, United States

Location

Related Publications (4)

• 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.

  PMID: 20933198 BACKGROUND

• 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.

  PMID: 20810473 BACKGROUND

• 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.

  PMID: 20430261 BACKGROUND

• 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.

  PMID: 17010808 BACKGROUND

MeSH Terms

Conditions

Systolic Murmurs

Condition Hierarchy (Ancestors)

Heart Murmurs; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Barry Greenberg, MD

  University of California, San Diego

  STUDY CHAIR

• Uri Elkayam, MD

  LAC+USC Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: December 1, 2010
• Study Start: January 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: March 1, 2014
• Last Updated: February 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)