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

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Chronic Heart Failure	Drug: Placebo; Drug: rhNRG-1 Dose 1; Drug: rhNRG-1 Dose 2	Phase 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 Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	120 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	January 2012
Actual Primary Completion Date :	December 2012
Actual Study Completion Date :	March 2014

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
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 Name: 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 Name: Neucardin

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Change from baseline in LVEF [ Time Frame: 30 days ]
   Compared to baseline and placebo

Secondary Outcome Measures :

1. Six (6) minute walk test [ Time Frame: Day 30, 90, 180, 365 ]
   Compared to baseline and placebo
2. Quality of Life Questionnaire (Kansas City Cardiomyopathy Questionnaire) [ Time Frame: Day 30, 90, 180 and 365 ]
   Compared to baseline and placebo
3. NYHA class status [ Time Frame: Day 30, 90, 180 and 365 ]
   Compared to baseline and placebo
4. All cause mortality and all cause hospitalization [ Time Frame: Days 30, 90, 180 and 365 ]
   Compared to baseline and placebo
5. Change in LVESV and LVEDV [ Time Frame: Day 30 ]
   Compared to baseline and placebo

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

Zensun Sci. & Tech. Co., Ltd.

Zensun USA Inc.

Investigators

Study Chair:	Barry Greenberg, MD	University of California, San Diego
Principal Investigator:	Uri Elkayam, MD	LAC+USC Medical Center

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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. Review.

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. Epub 2006 Sep 14.

Responsible Party:	Zensun Sci. & Tech. Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01251406 History of Changes
Other Study ID Numbers:	ZS-01-210
First Posted:	December 1, 2010
Last Update Posted:	August 6, 2014
Last Verified:	August 2014

Keywords provided by Zensun Sci. & Tech. Co., Ltd.:

Stable; Chronic Heart Failure; Systolic

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases