Clinical Trial to Evaluate the Efficacy and Safety of Recombinant Human Neuregulin-1 for Subcutaneous Administration in Patients With Chronic Systolic Heart Failure

A Multi-center, Randomized, Double-blind , Placebo Parallel Controlled, Standard Therapy Based Phase III Clinical Trial to Evaluate the Efficacy and Safety of Recombinant Human Neuregulin-1 for Subcutaneous Administration in Patients With Chronic Systolic Heart Failure

Evaluate the Efficacy and Safety of Recombinant Human Neuregulin-1 for Subcutaneous Administration in Patients With Chronic Systolic Heart Failure

Study Overview

• Status: Terminated
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: placebo; Drug: rhNRG-1; Drug: rhNRG-1; Drug: rhNRG-1

Detailed Description

1. Subcutaneous Administration of NRG-1 is well tolerated by CHF patients
2. Subcutaneous Administration of NRG-1 improves the cardiac function of CHF patients
3. Assessment of relative bioavailability of NRG-1 by Subcutaneous Administration

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Chaoyang Hospital, Capital Medical University
  • Beijing, China
    • Beijing Anzhen Hospital of Capital University of Medical Sciences
  • Beijing, China
    • Cardiovascular Institute & Fuwai Hospital, Chinese Academy of Medical Sciences
  • Beijing, China
    • General Hospital of People's Liberation Army

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age: 18-75 years old, no limitation in gender;
2. Left ventricular ejection fraction (LVEF) ≤ 40% (ECHO);
3. Patients with chronic heart failure (NYHA class II or III);
4. In the past one month, the clinical condition (including history, clinical symptoms and signs) was relatively stable;
5. Patients on standard treatment of chronic heart failure at the target dose or maximum tolerance dose for over 1 month ,or unchanged dose in last 1 month;
6. Understand and sign the informed consent form;

Exclusion Criteria:

1. Atrial fibrillation;
2. Subject underwent cardiac pacemaker treatment;
3. Subject underwent metal graft treatment;
4. Claustrophobia;
5. Acute myocardial infarction, cardiac ischemia indicated by 6-minute walk test, hypertrophic cardiomyopathy, constrictive pericarditis, significant valve disease or congenital heart disease, severe pulmonary hypertension;
6. Ischemic heart failure without the revascularization or undergone the revascularization within last 6 months;
7. Subject underwent cardiac surgery or cerebrovascular events within the previous six months;
8. Subjects who plan to have cardiac transplantation;
9. Severe hepatic and renal insufficiency (serum creatinine>2.0 mg /dl, AST or ALT is five times higher than the upper limit of normal range);
10. Subject needs mechanical ventilation;
11. Systolic blood pressure < 90mmHg, or > 160mmHg;
12. Chronic heart failure complicated with acute hemodynamic disturbance or acute decompensation within last 1 month;
13. Mobitz Type II or III° atrial ventricular block，severe ventricular arrhythmia (polymorphic and frequent premature ventricular beats, frequent non-sustained ventricular tachycardia);
14. Serum potassium<3.2mmol/L, or>5.5mmol/L;
15. Female subject is pregnant or plan to become pregnant
16. Childbearing-aged female subject who is unmarried or dose not bear child;
17. Subject with life expectancy less than 6 months as assessed by investigators;
18. Subject participated in any other clinical trial within the previous three months;
19. Subject with previous history of tumor, or current tumor patient, or subject with pre-cancerous disease manifested by pathological examination (such as ductal carcinoma in situ or cervical epithelial dysplasia)
20. Examinations (physical examination, X-ray examination, type-B ultrasonic detection or other methods) reveal that the subject has malignant mass, gland hyperplasia or adenoma with endocrine activity, or impact on heart, or endocrine function (such as pheochromocytoma, thyroid enlargement);
21. The Investigator deemed for whatever reason that the subject is not likely to complete the study or comply with the study procedures (due to administration or any other reason).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; Subcutaneous Administration:0.6 or 1.2ug/kg/day for 10days
Experimental: rhNRG-1; recombinant human neuregulin-1	Drug: rhNRG-1; Subcutaneous Administration:0.6ug/kg/day for 10days; Drug: rhNRG-1; Subcutaneous Administration 1.2ug/kg/day for 10 days; Drug: rhNRG-1; Vein infusion:0.6ug/kg/day for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
cardiac function measured by MRI	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac function	6-minute walk test, cardiac function classification(NYHA)，life quality score.	baseline, 30 days, 90day and180 days

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.
• Investigators: Principal Investigator: Runlin Gao, Cardiovascular Institute and Fuwai Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: September 28, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Actual): December 21, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: MRI; rhNRG-1; Chronic Heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic
• Other Study ID Numbers: ZS-01-302