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

Chronic Heart Failure Clinical Trial

— ZS-01-210  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01251406
• Other study ID #: ZS-01-210
• Status: Completed
• Phase: Phase 2
• Start date: January 2012
• Est. completion date: March 2014

Study information

• Verified date: April 2021
• Source: Zensun Sci. & Tech. Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 2014
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• Placebo
Daily subcutaneous administration for 8 hours a day for 10 days
• rhNRG-1 Dose 1
Daily subcutaneous administration for 8 hours a day for 10 days
• rhNRG-1 Dose 2
Daily subcutaneous administration for 8 hours a day for 10 days

Locations

Country	Name	City	State
United States	Clearwater Cardiovascular & Interventional Consultants, MD, PA	Clearwater	Florida
United States	University of Colorado Denver	Denver	Colorado
United States	East Texas Cardiology	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	MedPharmics, LLC.	Kenner	Louisiana
United States	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	Benchmark Research	Metairie	Louisiana
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	The Medical Center of Plano	Plano	Texas
United States	University of South Florida	Tampa	Florida
United States	Orange County Research Center	Tustin	California

Sponsors (2)

Lead Sponsor	Collaborator
Zensun Sci. & Tech. Co., Ltd.	Zensun USA Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in LVEF	Compared to baseline and placebo	30 days
Secondary	Six (6) minute walk test	Compared to baseline and placebo	Day 30, 90, 180, 365
Secondary	Quality of Life Questionnaire (Kansas City Cardiomyopathy Questionnaire)	Compared to baseline and placebo	Day 30, 90, 180 and 365
Secondary	NYHA class status	Compared to baseline and placebo	Day 30, 90, 180 and 365
Secondary	All cause mortality and all cause hospitalization	Compared to baseline and placebo	Days 30, 90, 180 and 365
Secondary	Change in LVESV and LVEDV	Compared to baseline and placebo	Day 30