Clinical trial NCT01251406: Efficacy and Safety of Human Neuregulin-1 to Treat Stable Chronic Heart Failure
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Heart Failure
Keywords: Stable
Chronic Heart Failure
Systolic
Lead sponsor: Zensun Sci. & Tech. Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Zensun USA Inc.
First posted: 2010-12-01
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Change from baseline in LVEF
timeFrame: 30 days
Secondary outcomes:
measure: Six (6) minute walk test
timeFrame: Day 30, 90, 180, 365
measure: Quality of Life Questionnaire (Kansas City Cardiomyopathy Questionnaire)
timeFrame: Day 30, 90, 180 and 365
measure: NYHA class status
timeFrame: Day 30, 90, 180 and 365
measure: All cause mortality and all cause hospitalization
timeFrame: Days 30, 90, 180 and 365
measure: Change in LVESV and LVEDV
timeFrame: Day 30
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: Metabolic Clinic and Research Center
state: California
city: Los Angeles
country: United States
facility: USC Cardiovascular Division
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Clearwater
country: United States
facility: Clearwater Cardiovascular & Interventional Consultants, MD, PA
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kenner
country: United States
facility: MedPharmics, LLC.
state: Louisiana
city: Metairie
country: United States
facility: Benchmark Research
state: Louisiana
city: Houston
country: United States
facility: East Texas Cardiology
state: Texas
city: Plano
country: United States
facility: The Medical Center of Plano
state: Texas
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
Study officials:
affiliation: University of California, San Diego
name: Barry Greenberg, MD
role: STUDY_CHAIR
affiliation: LAC+USC Medical Center
name: Uri Elkayam, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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. doi: 10.1016/j.jacc.2006.05.057. Epub 2006 Sep 14.