Evaluation of the Effect of Injectable Neucardin on Cardiac Function and Reversal Ventricular Remodeling in Patients With Chronic Systolic Heart Failure

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial Based on Standard Treatment to Evaluate the Effect of Injectable Neucardin on Cardiac Function and Reverse Ventricular Remodeling in Patients With Chronic Systolic Heart Failure

A multicenter, randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the effect of recombinant human Neuregulin-1 for injection on cardiac function and reverse ventricular remodeling in male patients with NT-proBNP ≤ 1700 pg/ml and female patients with NT-proBNP ≤ 4000 pg/ml and New York Heart Association class II-III chronic systolic heart failure, and to confirm its efficacy and safety.

Study Overview

• Status: Recruiting
• Conditions: Chronic Systolic Heart Failure
• Intervention / Treatment: Drug: Neucardin; Drug: Placebo

Detailed Description

This trial is planned to be conducted simultaneously in multiple clinical study sites nationwide, including 198 subjects, 99 subjects in the treatment group and 99 subjects in the placebo group.

Primary endpoint:

1.Response rate at 35 days of simultaneous reduction of LVESVI and LVEDVI by more than or equal to 20 ml/m2 (The proportion of the subjects achieving this criterion in each treatment group.)

Secondary endpoints:

1. Response rate at 35 day of LVESVI improvement greater than or equal to 25 ml/m2 ;
2. Response rate at 35 day of LVEDVI improvement greater than or equal to 25 ml/m2 ;
3. Change from baseline in LVEF, LVESV, LVEDV, LVESVI and LVEDVI at 35 days ;
4. 90-day response rate of LVESVI improved greater than or equal to 25ml/m2,LVEDVI improved greater than or equal to 25 ml/m2, and LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time ;
5. Change from baseline in LVEF, LVESV, LVEDV, LVESVI and LVEDVI at 90 days ;
6. Change from baseline in NYHA at 35 and 90 days ;
7. Change from baseline in quality of life at 35 and 90 days ;
8. Mortality during the study period.

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoyan Qin, ph.D; Phone Number: 138 86-021-50802627; Email: qinxiaoyan@zensun.com

Study Locations

• China
  • Beijing
    • Beijin, Beijing, China, 100037
      • Active, not recruiting
      • Fuwai Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100037
      • Active, not recruiting
      • Beijing Chao-Yang Hospital , Capital Medical University
    • Beijing, Beijing, China
      • Active, not recruiting
      • Beijing Anzhen Hospital , Capital Medical University
    • Beijing, Beijing, China
      • Active, not recruiting
      • Beijing Friendship Hospital , Capital Medical University
    • Beijing, Beijing, China
      • Active, not recruiting
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Active, not recruiting
      • Peking university People's Hospital
    • Beijing, Beijing, China
      • Active, not recruiting
      • The First Medical Center of General Hospital of Chinese People's Liberation Army
    • Beijing, Beijing, China
      • Active, not recruiting
      • Chinese people's liberation army general hospital No.6 medical center
  • Chongqing
    • Chongqing, Chongqing, China
      • Active, not recruiting
      • Chongqing Emergency Medical Center (Chongqing Fourth People's Hospital)
    • Chongqing, Chongqing, China
      • Active, not recruiting
      • Chongqing University Three Gorges Hospital
  • Fujian
    • Longyan, Fujian, China
      • Active, not recruiting
      • Longyan First Hospital
    • Xiamen, Fujian, China
      • Active, not recruiting
      • Xiamen Cardiovascular Hospital Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Active, not recruiting
      • First Affiliated Hospital of Sun Yat-sen University
    • Jieyang, Guangdong, China
      • Active, not recruiting
      • Guangdong Jieyang People's Hospital
    • Maoming, Guangdong, China
      • Active, not recruiting
      • Maoming People's Hospital
  • Guangxi Zhuang Autonomous Region
    • Liuzhou, Guangxi Zhuang Autonomous Region, China
      • Active, not recruiting
      • Liuzhou Worker's Hospital
    • Nanning, Guangxi Zhuang Autonomous Region, China
      • Active, not recruiting
      • People's Hospital of Guangxi Zhuang Autonomous Region
  • Hainan
    • Haikou, Hainan, China
      • Active, not recruiting
      • Haikou People's Hospital
    • Haikou, Hainan, China
      • Active, not recruiting
      • Hainan Provincial People's Hospital
  • Hebei
    • Baoding, Hebei, China
      • Active, not recruiting
      • Affiliated Hospital of Hebei University
    • Shijiazhuang, Hebei, China
      • Active, not recruiting
      • The First Hospital of Hebei Medical University
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Active, not recruiting
      • Daqing Oilfield General Hospital
    • Ha'erbin, Heilongjiang, China
      • Active, not recruiting
      • The First Affiliated Hospital Of Harbin Medical University
    • Qiqihar, Heilongjiang, China
      • Active, not recruiting
      • Qiqihar first hospital
  • Henan
    • Anyang, Henan, China
      • Active, not recruiting
      • Anyang People's Hospital (Anyang Central Hospital)
    • Kaifeng, Henan, China
      • Active, not recruiting
      • Huaihe Hospital of Henan University
    • Luoyang, Henan, China
      • Active, not recruiting
      • First Affiliated Hospital of Henan University of Science and Technology
    • Luoyang, Henan, China
      • Active, not recruiting
      • Luoyang Central Hospital
    • Nanyang, Henan, China
      • Active, not recruiting
      • NanYang First people's hospital
    • Nanyang, Henan, China
      • Active, not recruiting
      • Nanyang Central Hospital
    • Puyang, Henan, China
      • Active, not recruiting
      • General Hospital of Puyang Oilfield
    • Sanmenxia, Henan, China
      • Active, not recruiting
      • Sanmenxia Central Hospital
    • Shangqiu, Henan, China
      • Active, not recruiting
      • First People's Hospital of Shangqiu
    • Xinxiang, Henan, China
      • Active, not recruiting
      • The First Affiliated Hospital of Xinxiang Medical College
    • Xinxiang, Henan, China
      • Active, not recruiting
      • Xinxiang Central Hospital
    • Zhengzhou, Henan, China
      • Active, not recruiting
      • First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China
      • Active, not recruiting
      • The First Affiliated Hospital of Henan University
    • Zhumadian, Henan, China
      • Active, not recruiting
      • Zhumadian Central Hospital
  • Huanan
    • Chenzhou, Huanan, China
      • Active, not recruiting
      • Chenzhou First People's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Active, not recruiting
      • People's Hospital of Wuhan University
    • Wuhan, Hubei, China
      • Active, not recruiting
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China
      • Active, not recruiting
      • Wuhan Wuchang Hospital
    • Xiangyang, Hubei, China
      • Active, not recruiting
      • Xiangyang Central Hospital
    • Xiangyang, Hubei, China
      • Active, not recruiting
      • Xiangyang first people's hospital
  • Hunan
    • Changsha, Hunan, China
      • Active, not recruiting
      • People's Hospital of Hunan Provincial
    • Hengyang, Hunan, China
      • Active, not recruiting
      • South China University Affiliated South China Hospital
    • Hengyang, Hunan, China
      • Active, not recruiting
      • The Second Affiliated Hospital of Nanhua University
    • Yueyang, Hunan, China
      • Active, not recruiting
      • Yueyang Central Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Active, not recruiting
      • Jiangxi Provincial People's Hospital
  • Jiansu
    • Changzhou, Jiansu, China
      • Recruiting
      • Changzhou No.2 People's Hospital
      • Contact: Yuan Ji, M.D
    • Changzhou, Jiansu, China
      • Active, not recruiting
      • The First People's Hospital of Changzhou
    • Huai'an, Jiansu, China
      • Active, not recruiting
      • Huai'an First People's Hospital
    • Nanjing, Jiansu, China
      • Active, not recruiting
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiansu, China
      • Active, not recruiting
      • Zhongda Hospital Southeast University
    • Suzhou, Jiansu, China
      • Active, not recruiting
      • The First Affiliated Hospital of Soochow University
    • Suzhou, Jiansu, China
      • Active, not recruiting
      • The Suzhou Municipal Hospital
    • Xuzhou, Jiansu, China
      • Active, not recruiting
      • Affiliated Hospital of Xuzhou Medical University
    • Xuzhou, Jiansu, China
      • Active, not recruiting
      • Xuzhou Central Hospital
    • Yangzhou, Jiansu, China
      • Active, not recruiting
      • Subei People's Hospital
  • Jilin
    • Changchun, Jilin, China
      • Active, not recruiting
      • China-Japan Union Hospital of Jilin University
    • Changchun, Jilin, China
      • Active, not recruiting
      • Jilin University Second Hospital
    • Changchun, Jilin, China
      • Active, not recruiting
      • The First Hospital of Jilin University
  • Liaoning
    • Anshan, Liaoning, China
      • Active, not recruiting
      • Ansteel Group Genral Hospital
    • Benxi, Liaoning, China
      • Active, not recruiting
      • Benxi Central Hospital
    • Dalian, Liaoning, China
      • Active, not recruiting
      • The First Affiliated Hospital of Dalian Medical University
    • Dalian, Liaoning, China
      • Active, not recruiting
      • Zhongshan Hospital Affiliated to Dalian University
    • Shenyang, Liaoning, China
      • Active, not recruiting
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Active, not recruiting
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Active, not recruiting
      • Central Hospital Affiliated to Shenyang Medical College
    • Shenyang, Liaoning, China
      • Active, not recruiting
      • Liaoning Provincial People's Hospital
  • Nanyang
    • Henan, Nanyang, China
      • Active, not recruiting
      • Nanyang Second People's Hospital
  • Shandong
    • Heze, Shandong, China
      • Active, not recruiting
      • Heze Municipal Hospital
    • Jinan, Shandong, China
      • Active, not recruiting
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Active, not recruiting
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China
      • Active, not recruiting
      • Shandong province Qianfoshan hospital
    • Linyi, Shandong, China
      • Active, not recruiting
      • Linyi People's Hospital
    • Tai'an, Shandong, China
      • Active, not recruiting
      • Tai'an City Central Hospital
    • Zibo, Shandong, China
      • Active, not recruiting
      • Zibo Municipal Hospital
  • Shangdong
    • Jining, Shangdong, China
      • Active, not recruiting
      • Affiliated Hospital of Jining Medical College
    • Jining, Shangdong, China
      • Active, not recruiting
      • Jining First People's Hospital
    • Zaozhuang, Shangdong, China
      • Active, not recruiting
      • Zaozhuang Municipal Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Active, not recruiting
      • Putuo District Central Hospital of Shanghai
    • Shanghai, Shanghai, China
      • Active, not recruiting
      • Shanghai Baoshan District Wusong Central Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • Active, not recruiting
      • The First Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China
      • Active, not recruiting
      • Shanxi Provincial Cardiovascular Hospital
    • Xi'an, Shanxi, China
      • Active, not recruiting
      • The First Affiliated Hospital of Xi 'an Jiaotong University
    • Xi'an, Shanxi, China
      • Active, not recruiting
      • Xi'an Gaoxin Hospital
    • Xianyang, Shanxi, China
      • Active, not recruiting
      • Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine
    • Xianyang, Shanxi, China
      • Active, not recruiting
      • Xianyang First People's Hospital
    • Xianyang, Shanxi, China
      • Active, not recruiting
      • Xianyang Hospital of Yan 'an University
  • Sichuan
    • Chengdu, Sichuan, China
      • Active, not recruiting
      • The Fifth People's Hospital of Chengdu
    • Mianyang, Sichuan, China
      • Active, not recruiting
      • Mianyang Central Hospital
  • Yunnan
    • Dali, Yunnan, China
      • Active, not recruiting
      • The First Affiliated Hospital of Dali University
    • Kunming, Yunnan, China
      • Active, not recruiting
      • Fuwai Yunnan Cardiovascular Hospital
    • Kunming, Yunnan, China
      • Active, not recruiting
      • The First People's Hospital of Yunnan Province
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Active, not recruiting
      • The First Affiliated Hospital , Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • Active, not recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hanzhou, Zhejiang, China
      • Active, not recruiting
      • Affiliated Hospital of Hangzhou Normal University
    • Hanzhou, Zhejiang, China
      • Active, not recruiting
      • Sir Run Run Shaw Hospital
    • Jiaxing, Zhejiang, China
      • Active, not recruiting
      • Jiaxing First Hospital
    • Ningbo, Zhejiang, China
      • Active, not recruiting
      • Ningbo Huamei Hospital, University of Chinese Academy of Sciences (Ningbo Second Hospital)
    • Ningbo, Zhejiang, China
      • Active, not recruiting
      • The First Hospital of Ningbo
    • Wenzhou, Zhejiang, China
      • Active, not recruiting
      • First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18-75 years, male or female;
2. Definite diagnosis of heart failure for 6 months or more, current stable disease, NYHA class II-III, left ventricular ejection fraction (LVEF) ≤ 40%(echocardiographic modified Simpson's method measurement ≤ 40% at screening, and CMR measurement ≤ 40% at baseline);
3. NT-proBNP ≤1700 pg/ml in males and ≤4000pg/ml in females (detected by Roche kit in central laboratory);
4. Receiving standard basic treatment for heart failure for at least 3 months, and did not change the type and dose of heart failure treatment drugs within 1 month;
5. Understand and sign the informed consent form.

Exclusion Criteria:

1. Unable to receive CMR examination, such as patients with pacemakers, ICDs, CRTs, or other similar devices contraindicated for CMR, claustrophobia, atrial fibrillation during the screening period, or inability to cooperate with air-closed activities required for CMR testing;
2. Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction, constrictive pericarditis, significant and uncorrected valvular heart disease, severe valvular regurgitation or severe stenosis, congenital heart disease requiring surgical treatment but not surgical treatment, primary pulmonary hypertension or secondary severe pulmonary hypertension (≥ 70 mmHg), and right heart failure due to pulmonary disease;
3. Patients suffering from proliferative glands or adenomas with endocrine activity which may affect cardiac function or endocrine function, such as pheochromocytoma, thyromegaly, etc. (patients with euthyroid thyroid nodules do not need to be excluded);
4. LVESVi less than 135 ml/m2 at baseline;
5. Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;
6. History of heart transplantation, use of ventricular assist devices (VADs) or preparation for heart transplantation, VADs;
7. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;
8. Subjects with chronic heart failure with acute hemodynamic disturbance or acute decompensation within the past 1 month (symptoms and signs prove that chronic heart failure is aggravated and intravenous drug therapy is required);
9. Angina pectoris within the past 3 months;
10. Myocardial infarction, cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;
11. Serious ventricular arrhythmias (sustained ventricular tachycardia or other conditions that the investigator considers necessary to exclude);
12. Clinical diagnosis of pericardial effusion, pleural effusion or imaging showed pericardial effusion (greater than 50ml or 3 mm or a small amount or more) or pleural effusion (greater than 200ml or 10 mm);
13. Liver and kidney dysfunction and chronic liver disease may have a potential impact on liver function (such as active chronic hepatitis, etc.), non-heart failure causes of bilirubin or alkaline phosphatase > 2 times the upper limit of normal, aspartate aminotransferase and/or alanine aminotransferase > 3 times the upper limit of normal, eGFR calculated using MDRD method < 30 ml/min/1.73 m2;
14. Systolic blood pressure < 90 mmHg or > 160 mmHg;
15. Serum K + < 3.2 mmol/L or > 5.5 mmol/L;
16. Women of childbearing potential who plan to become pregnant within 2 years (women of childbearing potential are defined as all women with physical ability to become pregnant), pregnant or lactating women;
17. Previous history of cancer or current cancer, or pathological examination confirmed precancerous lesions (Such as ductal carcinoma in situ of the breast, or atypical hyperplasia of the cervix), or through the examination (physical examination, X-ray examination or B ultrasound examination or other means) found in vivo malignant mass subjects;
18. The investigator judges that the survival time is expected to be less than 6 months;
19. Participated in any drug clinical trials within the first 3 months;
20. Severe neurological disease (Alzheimer's disease, progressive parkinsonism);
21. Subjects who are unable to complete this study or fail to comply with the requirements of this study (due to administrative reasons or other reasons), as judged by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational drug group; Neucardin+standard basic therapeutic medication	Drug: Neucardin; 10 days IV infusion of 0.6 ug/kg/day; Other Names: Recombinant human Neuregulin-1 for Injection
Placebo Comparator: placebo group; Placebo + standard basic therapeutic medication	Drug: Placebo; 10 days IV infusion of 0 ug/kg/day; Other Names: Excipients of recombinant human neuregulin-1 freeze dried for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate at 35 days of simultaneous reduction of LVESVI and LVEDVI by more than or equal to 20 ml/m2 (The proportion of the subjects achieving this criterion in each treatment group)	Response rate at 35 days of simultaneous reduction of LVESVI and LVEDVI by more than or equal to 20 ml/m2 (The proportion of the subjects achieving this criterion in each treatment group)	Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate at 35 day of left ventricular end systolic volume index (LVESVI) improvement greater than or equal to 25 ml/m2;	Response rate at 35 day of LVESVI improvement greater than or equal to 25 ml/m2;	Day 35
Response rate at 35 day of left ventricular end diastolic volume index (LVEDVI) improvement greater than or equal to 25 ml/m2;	Response rate at 35 day of LVEDVI improvement greater than or equal to 25 ml/m2;	Day 35
Change from baseline in left ventricular ejection fraction (LVEF) at 35 days;	Change from baseline in LVEF at 35 days;	Day 35
Change from baseline in left ventricular end systolic volume (LVESV) at 35 days;	Change from baseline in LVESV at 35 days;	Day 35
Change from baseline in left ventricular end diastolic volume (LVEDV) at 35 days;	Change from baseline in LVEDV at 35 days;	Day 35
Change from baseline in LVESVI and LVEDVI at 35 days;	Change from baseline in LVESVI and LVEDVI at 35 days;	Day 35
90-day response rate of LVESVI improved greater than or equal to 25 ml/m2;	90-day response rate of LVESVI improved greater than or equal to 25 ml/m2;	Day 90
90-day response rate of LVEDVI improved greater than or equal to 25 ml/m2;	90-day response rate of LVEDVI improved greater than or equal to 25 ml/m2;	Day 90
90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time;	90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time;	Day 90
Change from baseline in LVEF at 90 days;	Change from baseline in LVEF at 90 days;	Day 90
Change from baseline in LVESV at 90 days;	Change from baseline in LVESV at 90 days;	Day 90
Change from baseline in LVEDV at 90 days;	Change from baseline in LVEDV at 90 days;	Day 90
Change from baseline in LVESVI and LVEDVI at 90 days;	Change from baseline in LVESVI and LVEDVI at 90 days;	Day 90
Change from baseline in New York Heart Association (NYHA) at 35 and 90 days;	Change from baseline in NYHA at 35 and 90 days;	Day 35 and Day 90
Change from baseline in quality of life at 35 and 90 days;	Change from baseline in quality of life at 35 and 90 days;The benefit of patients is reflected by the quality of life score table.	Day 35 and Day 90
Mortality during the study period;	Mortality during the study period;	Through study completion, an estimation of average of 1 year

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.
• Investigators: Principal Investigator: Jian Zhang, M.D, Chinese Academy of Medical Sciences, Fuwai Hospital; Principal Investigator: Mulei Chen, M.D, Beijing Chaoyang Hospital affiliated to Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 2, 2023
• First Submitted That Met QC Criteria: July 9, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: CHF Neucardin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Murmurs; Heart Failure; Systolic Murmurs; Heart Failure, Systolic; Ventricular Remodeling
• Other Study ID Numbers: ZS-01-308B

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