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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: rhNRG-1 Dose 1
* Drug: rhNRG-1 Dose 2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stable, Chronic Heart Failure, Systolic