Evaluate the Effect of Injectable Neucardin on the Cardiac Function of Subjects With Chronic Systolic Heart Failure

A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Evaluate the Effect of Injectable Neucardin on the Cardiac Function of Subjects With Chronic Systolic Heart Failure on Standard Heart Failure Therapy

A multi-center, randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the effect of injectable Neucardin on the heart function in male patients with NT-proBNP ≤ 1700 pg/ml and female patients with NT-proBNP ≤ 4000 pg/ml, NYHA II-III chronic systolic heart failure, and to confirm its efficacy and safety.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Systolic Heart Failure
• Intervention / Treatment: Drug: Recombinant human Neuregulin for injection; Drug: Placebo

Detailed Description

This trial is planned to be conducted simultaneously in multiple domestic clinical research site, and a total of 140 subjects will be enrolled, including 70 subjects in the investigational drug group and 70 subjects in the placebo group.

Primary endpoint: LVESVI change from baseline on day 30 Secondary endpoints: LVEF Change from baseline on day 30 and day 90. LVESV, LVEDV, LVEDVI change from baseline on day 30. LVESV, LVESVI, LVEDV, LVEDVI change from baseline on day 90. NT-proBNP change from baseline on day 30 and day 90. NYHA class change from baseline on day 30 and day 90.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing Three Gorges Central Hospital
  • Hainan
    • Haikou, Hainan, China
      • Haikou People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-75 years, male or female;
2. Confirmed diagnosis of heart failure, in stable condition currently, NYHA class II-III, left ventricular ejection fraction (LVEF)≤40% (measured by echocardiography with modified Simpson's method at Screening 1, and measured by CMR at Screening 2 and baseline);
3. Male NT-proBNP ≤1700 pg/ml or female NT-proBNP≤4000 pg/ml (detected by Roche kit in the central laboratory at screening 1);
4. Receiving standard basic therapeutic medication for heart failure for more than 3 months, at the target dose or maximum tolerated dose for more than 1 month, or no change in dose within the last 1 month;
5. Understand and sign the informed consent form.

Exclusion Criteria:

1. Atrial fibrillation during the screening period;
2. Conditions limiting CMR examination, such as installation of pacemakers, ICDs, CRTs or other similar devices contraindicated for CMR, or have claustrophobia;
3. Hypertrophic cardiomyopathy with outflow tract obstruction, constrictive pericarditis, significant and uncorrected valvular heart disease (severe regurgitation or severe stenosis or valvular disease requiring surgery), congenital heart disease requiring surgery but not yet undergoing surgical treatment, primary pulmonary hypertension or secondary severe pulmonary hypertension (≥ 70 mmHg);
4. Right heart failure due to lung disease;
5. Subjects with chronic heart failure complicated with acute hemodynamic disturbance or acute decompensation within recent 1 month (symptoms and signs indicate chronic heart failure is aggravated, and intravenous drug therapy may be required);
6. Angina pectoris within 3 months;
7. Myocardial infarction within the past 6 months;
8. Cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;
9. Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;
10. History of heart transplantation, use of ventricular assist device (VAD) or preparation for heart transplantation, VAD;
11. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;
12. Serious arrhythmia (sustained ventricular tachycardia or other conditions meet the criteria according to the investigator's judgement );
13. Clinical diagnosis of pericardial effusion, pleural effusion or B ultrasound showed pericardial effusion (greater than 50ml or 3 mm) or pleural effusion (greater than 200ml or 10 mm);
14. Liver or kidney dysfunction, chronic liver disease may have a potential impact on liver function, non-heart failure induced bilirubin or alkaline phosphatase > 2 times the upper limit of normal, aspartate aminotransferase or alanine aminotransferase > 3 times the upper limit of normal, eGFR calculated using the MDRD method < 30 ml/min/1.73m2 ;
15. Systolic blood pressure < 90 mmHg or > 160 mmHg;
16. Blood K + < 3.2 mmol/L or > 5.5 mmol/L;
17. Subjects with an absolute change in LVEF > 5% as detected by CMR between screening 2 and baseline;
18. Women of childbearing age who are planning to become pregnant within 2 years (women of childbearing age are defined as all women with physiological capability to become pregnant), and pregnant or lactating women;
19. Patients whose survival time is expected to be less than 6 months as judged by the investigator;
20. Those who have participated in any drug clinical trial within the previous 3 months;
21. Severe neurological disorders (Alzheimer's disease, progressive parkinsonism);
22. The subjects with tumor history or is suffering from tumor now, or with precancerous lesions confirmed by pathological examination (such as breast ductal carcinoma in situ, or cervical dysplasia), or with malignant mass found by examination (physical examination, X-ray examination or B ultrasound examination or other means);
23. The subjects with proliferative glands or adenomas that are found to have endocrine activity that affects cardiac function or endocrine function detected by examinations (physical examination, X-ray examination, B ultrasound examination or other means), such as pheochromocytoma, thyromegaly, etc. (patients with euthyroid thyroid or normal thyroid function do not need to be excluded);
24. The subject, in the judgment of the Investigator, is unable to complete the study or to comply with the requirements of the study (for administrative or other reasons).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational drug group; Injectable Neucardin + standard basic therapeutic medication	Drug: Recombinant human Neuregulin for injection; 10 hours per day i.v. drip for the first 10 days (0.6ug/kg/day); Other Names: Neucardin
Placebo Comparator: Placebo group; placebo + standard basic therapeutic medication	Drug: Placebo; 10 hours per day i.v. drip for the first 10 days (0ug/kg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 30	Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction(LVEF) Change from baseline on day 30 and day 90	Left Ventricular Ejection Fraction(LVEF) Change from baseline	Day 30 and Day 90
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 90	Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline	Day 90
Left Ventricular End-Systolic Volume(LVESV)change from baseline on day 30 and day 90	Left Ventricular End-Systolic Volume(LVESV)change from baseline	Day 30 and Day 90
Left Ventricular End-Diastolic Volume(LVEDV)change from baseline on day 30 and day 90	Left Ventricular End-Diastolic Volume(LVEDV)change from baseline	Day 30 and Day 90
Left Ventricular End-Diastolic Volume Index(LVEDVI )change from baseline on day 30 and day 90	Left Ventricular End-Diastolic Volume Index(LVEDVI )	Day 30 and Day 90
N-Terminal pro-Brain Natriuretic Peptide(NT-proBNP) change from baseline on day 30 and day 90	N-Terminal pro-Brain Natriuretic Peptide(NT-proBNP) change from baseline	Day 30 and Day 90
New York Heart Association(NYHA) class change from baseline on day 30 and day 90	New York Heart Association(NYHA) class change from baseline	Day 30 and day 90

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.
• Investigators: Principal Investigator: Xinchun Yang, M.D, Beijing Chao Yang Hospital; Principal Investigator: Aidong Shen, M.D, Beijing Friendship Hospital; Principal Investigator: Wei Dong, M.D, Chinese PLA General Hospital; Principal Investigator: Huaming Mou, M.D, Chongqing Three Gorges Central Hospital; Principal Investigator: Fanbo Meng, M.D, China-Japan Union Hospital, Jilin University; Principal Investigator: Yushi Wang, M.D, The First Hospital of Jilin University; Principal Investigator: Ying Liu, M.D, The First Affiliated Hospital of Dalian Medical University; Principal Investigator: Zongjun Liu, M.D, Shanghai Putuo District Central Hospital; Principal Investigator: Shaowen Liu, M.D, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Principal Investigator: Tingbo Jiang, M.D, First Affiliated Hospital of Suzhou Medical College; Principal Investigator: Guohai Su, M.D, Jinan Central Hospital; Principal Investigator: Ming Zhong, M.D, Qilu Hospital of Shandong University; Principal Investigator: Gangqiong Liu, M.D, The First Affiliated hospital of Zhengzhou University; Principal Investigator: Yinglong Hou, M.D, Qianfoshan Hospital; Principal Investigator: Ping Qiao, M.D, Hainan General Hospital; Principal Investigator: Shijuan Lu, M.D, Haikou People's Hospital; Principal Investigator: Shumei Ma, M.D, Shengjing Hospital; Principal Investigator: Shouyan Zhang, M.D, Luoyang Central Hospital; Principal Investigator: Jianqiang Peng, M.D, Hunan Provincial People's Hospital; Principal Investigator: Yugang Dong, M.D, The First Affiliated Hospital, Zhongshan University; Principal Investigator: Huanzhen Chen, M.D, The First Affiliated Hospital of Shanxi Medical University; Principal Investigator: Huiyuan Han, M.D, Shanxi Cardiovascular Hospital; Principal Investigator: Mulei Chen, M.D, Beijing Chao Yang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Anticipated): February 20, 2022
• Study Completion (Anticipated): May 20, 2022

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Murmurs; Heart Failure; Systolic Murmurs; Heart Failure, Systolic
• Other Study ID Numbers: ZS-01-308

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Zensun ensures that the key information about the design of this protocol will be published in a publicly available database such as www.clinicaltrials.gov. After the end of the trial, Zensun will assist the study site to objectively summarize the trial results, use appropriate statistical methods to analyze the trial data, objectively evaluate the safety and efficacy of the drug according to the results, and make a complete written summary report of the clinical trial. Study results will be submitted for publication and/or publication in a publicly available database. If other individuals or institutions related to this study want to publish or publish the study results or related data, they need to obtain the consent of the sponsor in advance. If the sponsor needs to include the name of the investigators in any publication or advertisement, the consent of the investigator should be obtained.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No