Evaluate the Effect of Injectable Neucardin on the Cardiac Function of Subjects With Chronic Systolic Heart Failure
Primary Purpose
Chronic Systolic Heart Failure
Status
Active
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Recombinant human Neuregulin for injection
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Systolic Heart Failure
Eligibility Criteria
Inclusion Criteria:
- Aged 18-75 years, male or female;
- 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);
- Male NT-proBNP ≤1700 pg/ml or female NT-proBNP≤4000 pg/ml (detected by Roche kit in the central laboratory at screening 1);
- 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;
- Understand and sign the informed consent form.
Exclusion Criteria:
- Atrial fibrillation during the screening period;
- Conditions limiting CMR examination, such as installation of pacemakers, ICDs, CRTs or other similar devices contraindicated for CMR, or have claustrophobia;
- 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);
- Right heart failure due to lung disease;
- 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);
- Angina pectoris within 3 months;
- Myocardial infarction within the past 6 months;
- Cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;
- Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;
- History of heart transplantation, use of ventricular assist device (VAD) or preparation for heart transplantation, VAD;
- Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;
- Serious arrhythmia (sustained ventricular tachycardia or other conditions meet the criteria according to the investigator's judgement );
- 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);
- 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 ;
- Systolic blood pressure < 90 mmHg or > 160 mmHg;
- Blood K + < 3.2 mmol/L or > 5.5 mmol/L;
- Subjects with an absolute change in LVEF > 5% as detected by CMR between screening 2 and baseline;
- 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;
- Patients whose survival time is expected to be less than 6 months as judged by the investigator;
- Those who have participated in any drug clinical trial within the previous 3 months;
- Severe neurological disorders (Alzheimer's disease, progressive parkinsonism);
- 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);
- 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);
- 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).
Sites / Locations
- Chongqing Three Gorges Central Hospital
- Haikou People's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Investigational drug group
Placebo group
Arm Description
Injectable Neucardin + standard basic therapeutic medication
placebo + standard basic therapeutic medication
Outcomes
Primary Outcome Measures
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 30
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline
Secondary Outcome Measures
Left Ventricular Ejection Fraction(LVEF) Change from baseline on day 30 and day 90
Left Ventricular Ejection Fraction(LVEF) Change from baseline
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 90
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline
Left Ventricular End-Systolic Volume(LVESV)change from baseline on day 30 and day 90
Left Ventricular End-Systolic Volume(LVESV)change from baseline
Left Ventricular End-Diastolic Volume(LVEDV)change from baseline on day 30 and day 90
Left Ventricular End-Diastolic Volume(LVEDV)change from baseline
Left Ventricular End-Diastolic Volume Index(LVEDVI )change from baseline on day 30 and day 90
Left Ventricular End-Diastolic Volume Index(LVEDVI )
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
New York Heart Association(NYHA) class change from baseline on day 30 and day 90
New York Heart Association(NYHA) class change from baseline
Full Information
NCT ID
NCT04468529
First Posted
July 6, 2020
Last Updated
February 7, 2022
Sponsor
Zensun Sci. & Tech. Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04468529
Brief Title
Evaluate the Effect of Injectable Neucardin on the Cardiac Function of Subjects With Chronic Systolic Heart Failure
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 10, 2020 (Actual)
Primary Completion Date
February 20, 2022 (Anticipated)
Study Completion Date
May 20, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zensun Sci. & Tech. Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Systolic Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a multi-center, randomized, double-blind, standard therapy based, placebo-controlled parallel study.
Masking
Participant
Masking Description
It is planned to conduct the study in several domestic clinical research sites at the same time. A total of 140 subjects will be enrolled, including 70 subjects in the investigational drug group and 70 subjects in the control group.
Allocation
Randomized
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Investigational drug group
Arm Type
Experimental
Arm Description
Injectable Neucardin + standard basic therapeutic medication
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
placebo + standard basic therapeutic medication
Intervention Type
Drug
Intervention Name(s)
Recombinant human Neuregulin for injection
Other Intervention Name(s)
Neucardin
Intervention Description
10 hours per day i.v. drip for the first 10 days (0.6ug/kg/day)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
10 hours per day i.v. drip for the first 10 days (0ug/kg/day)
Primary Outcome Measure Information:
Title
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 30
Description
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
Left Ventricular Ejection Fraction(LVEF) Change from baseline on day 30 and day 90
Description
Left Ventricular Ejection Fraction(LVEF) Change from baseline
Time Frame
Day 30 and Day 90
Title
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 90
Description
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline
Time Frame
Day 90
Title
Left Ventricular End-Systolic Volume(LVESV)change from baseline on day 30 and day 90
Description
Left Ventricular End-Systolic Volume(LVESV)change from baseline
Time Frame
Day 30 and Day 90
Title
Left Ventricular End-Diastolic Volume(LVEDV)change from baseline on day 30 and day 90
Description
Left Ventricular End-Diastolic Volume(LVEDV)change from baseline
Time Frame
Day 30 and Day 90
Title
Left Ventricular End-Diastolic Volume Index(LVEDVI )change from baseline on day 30 and day 90
Description
Left Ventricular End-Diastolic Volume Index(LVEDVI )
Time Frame
Day 30 and Day 90
Title
N-Terminal pro-Brain Natriuretic Peptide(NT-proBNP) change from baseline on day 30 and day 90
Description
N-Terminal pro-Brain Natriuretic Peptide(NT-proBNP) change from baseline
Time Frame
Day 30 and Day 90
Title
New York Heart Association(NYHA) class change from baseline on day 30 and day 90
Description
New York Heart Association(NYHA) class change from baseline
Time Frame
Day 30 and day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18-75 years, male or female;
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);
Male NT-proBNP ≤1700 pg/ml or female NT-proBNP≤4000 pg/ml (detected by Roche kit in the central laboratory at screening 1);
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;
Understand and sign the informed consent form.
Exclusion Criteria:
Atrial fibrillation during the screening period;
Conditions limiting CMR examination, such as installation of pacemakers, ICDs, CRTs or other similar devices contraindicated for CMR, or have claustrophobia;
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);
Right heart failure due to lung disease;
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);
Angina pectoris within 3 months;
Myocardial infarction within the past 6 months;
Cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;
Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;
History of heart transplantation, use of ventricular assist device (VAD) or preparation for heart transplantation, VAD;
Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;
Serious arrhythmia (sustained ventricular tachycardia or other conditions meet the criteria according to the investigator's judgement );
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);
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 ;
Systolic blood pressure < 90 mmHg or > 160 mmHg;
Blood K + < 3.2 mmol/L or > 5.5 mmol/L;
Subjects with an absolute change in LVEF > 5% as detected by CMR between screening 2 and baseline;
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;
Patients whose survival time is expected to be less than 6 months as judged by the investigator;
Those who have participated in any drug clinical trial within the previous 3 months;
Severe neurological disorders (Alzheimer's disease, progressive parkinsonism);
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);
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);
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xinchun Yang, M.D
Organizational Affiliation
Beijing Chao Yang Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Aidong Shen, M.D
Organizational Affiliation
Beijing Friendship Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wei Dong, M.D
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Huaming Mou, M.D
Organizational Affiliation
Chongqing Three Gorges Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fanbo Meng, M.D
Organizational Affiliation
China-Japan Union Hospital, Jilin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yushi Wang, M.D
Organizational Affiliation
The First Hospital of Jilin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ying Liu, M.D
Organizational Affiliation
The First Affiliated Hospital of Dalian Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zongjun Liu, M.D
Organizational Affiliation
Shanghai Putuo District Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shaowen Liu, M.D
Organizational Affiliation
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tingbo Jiang, M.D
Organizational Affiliation
First Affiliated Hospital of Suzhou Medical College
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Guohai Su, M.D
Organizational Affiliation
Jinan Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ming Zhong, M.D
Organizational Affiliation
Qilu Hospital of Shandong University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gangqiong Liu, M.D
Organizational Affiliation
The First Affiliated Hospital of Zhengzhou University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yinglong Hou, M.D
Organizational Affiliation
Qianfoshan Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ping Qiao, M.D
Organizational Affiliation
Hainan General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shijuan Lu, M.D
Organizational Affiliation
Haikou People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shumei Ma, M.D
Organizational Affiliation
Shengjing Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shouyan Zhang, M.D
Organizational Affiliation
Luoyang Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jianqiang Peng, M.D
Organizational Affiliation
Hunan Provincial People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yugang Dong, M.D
Organizational Affiliation
The First Affiliated Hospital, Zhongshan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Huanzhen Chen, M.D
Organizational Affiliation
The First Affiliated Hospital of Shanxi Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Huiyuan Han, M.D
Organizational Affiliation
Shanxi Cardiovascular Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mulei Chen, M.D
Organizational Affiliation
Beijing Chao Yang Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chongqing Three Gorges Central Hospital
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
Haikou People's Hospital
City
Haikou
State/Province
Hainan
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Learn more about this trial
Evaluate the Effect of Injectable Neucardin on the Cardiac Function of Subjects With Chronic Systolic Heart Failure
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