Clinical trial NCT05949801: Evaluation of the Effect of Injectable Neucardin on Cardiac Function and Reversal Ventricular Remodeling in Patients With Chronic Systolic Heart Failure
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Systolic Heart Failure
Keywords: CHF Neucardin
Lead sponsor: Zensun Sci. & Tech. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-18
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Day 35
Secondary outcomes:
measure: Response rate at 35 day of left ventricular end systolic volume index (LVESVI) improvement greater than or equal to 25 ml/m2;
timeFrame: Day 35
measure: Response rate at 35 day of left ventricular end diastolic volume index (LVEDVI) improvement greater than or equal to 25 ml/m2;
timeFrame: Day 35
measure: Change from baseline in left ventricular ejection fraction (LVEF) at 35 days;
timeFrame: Day 35
measure: Change from baseline in left ventricular end systolic volume (LVESV) at 35 days;
timeFrame: Day 35
measure: Change from baseline in left ventricular end diastolic volume (LVEDV) at 35 days;
timeFrame: Day 35
measure: Change from baseline in LVESVI and LVEDVI at 35 days;
timeFrame: Day 35
measure: 90-day response rate of LVESVI improved greater than or equal to 25 ml/m2;
timeFrame: Day 90
measure: 90-day response rate of LVEDVI improved greater than or equal to 25 ml/m2;
timeFrame: Day 90
measure: 90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time;
timeFrame: Day 90
measure: Change from baseline in LVEF at 90 days;
timeFrame: Day 90
measure: Change from baseline in LVESV at 90 days;
timeFrame: Day 90
measure: Change from baseline in LVEDV at 90 days;
timeFrame: Day 90
measure: Change from baseline in LVESVI and LVEDVI at 90 days;
timeFrame: Day 90
measure: Change from baseline in New York Heart Association (NYHA) at 35 and 90 days;
timeFrame: Day 35 and Day 90
measure: Change from baseline in quality of life at 35 and 90 days;
timeFrame: Day 35 and Day 90
measure: Mortality during the study period;
timeFrame: Through study completion, an estimation of average of 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital , Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Anzhen Hospital , Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital , Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Chinese people's liberation army general hospital No.6 medical center
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: The First Medical Center of General Hospital of Chinese People's Liberation Army
state: Beijing
city: Beijin
country: China
facility: Fuwai Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Chongqing
country: China
facility: Chongqing Emergency Medical Center (Chongqing Fourth People's Hospital)
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Longyan
country: China
facility: Longyan First Hospital
state: Fujian
city: Xiamen
country: China
facility: Xiamen Cardiovascular Hospital Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Jieyang
country: China
facility: Guangdong Jieyang People's Hospital
state: Guangdong
city: Maoming
country: China
facility: Maoming people's hospital
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou worker's hospital
state: Guangxi Zhuang Autonomous Region
city: Nanning
country: China
facility: People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi Zhuang Autonomous Region
city: Haikou
country: China
facility: Haikou People's Hospital
state: Hainan
city: Haikou
country: China
facility: Hainan Provincial People's Hospital
state: Hainan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Ha'erbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Qiqihar
country: China
facility: Qiqihar first hospital
state: Heilongjiang
city: Anyang
country: China
facility: Anyang People's Hospital (Anyang Central Hospital)
state: Henan
city: Kaifeng
country: China
facility: Huaihe Hospital of Henan University
state: Henan
city: Luoyang
country: China
facility: First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang First People's Hospital
state: Henan
city: Puyang
country: China
facility: General Hospital of Puyang Oilfield
state: Henan
city: Sanmenxia
country: China
facility: Sanmenxia Central Hospital
state: Henan
city: Shangqiu
country: China
facility: First People's Hospital of Shangqiu
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Xinxiang
country: China
facility: Xinxiang central hospital
state: Henan
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Henan University
state: Henan
city: Zhumadian
country: China
facility: Zhumadian Central Hospital
state: Henan
city: Chenzhou
country: China
facility: Chenzhou First People's Hospital
state: Huanan
city: Wuhan
country: China
facility: People's Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Wuhan Wuchang Hospital
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang first people's hospital
state: Hubei
city: Changsha
country: China
facility: People's Hospital of Hunan Provincial
state: Hunan
city: Hengyang
country: China
facility: South China University Affiliated South China Hospital
state: Hunan
city: Hengyang
country: China
facility: The Second Affiliated Hospital of Nanhua University
state: Hunan
city: Yueyang
country: China
facility: Yueyang Central Hospital
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital
state: Jiansu
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiansu
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiansu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiansu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiansu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiansu
city: Suzhou
country: China
facility: The Suzhou Municipal Hospital
state: Jiansu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiansu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiansu
city: Yangzhou
country: China
facility: Subei people's hospital
state: Jiansu
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin University Second Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Anshan
country: China
facility: Ansteel Group Genral Hospital
state: Liaoning
city: Benxi
country: China
facility: Benxi Central Hospital
state: Liaoning
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Dalian
country: China
facility: Zhongshan Hospital Affiliated to Dalian University
state: Liaoning
city: Shenyang
country: China
facility: Central Hospital Affiliated to Shenyang Medical College
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Provincial People's Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Henan
country: China
facility: Nanyang Second People's Hospital
state: Nanyang
city: Heze
country: China
facility: Heze Municipal Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Province Qianfoshan Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Tai'an
country: China
facility: Tai'an City Central Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Municipal Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical College
state: Shangdong
city: Jining
country: China
facility: Jining first people's hospital
state: Shangdong
city: Zaozhuang
country: China
facility: Zaozhuang municipal hospital
state: Shangdong
city: Shanghai
country: China
facility: Putuo District Central Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Baoshan District Wusong Central Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Cardiovascular Hospital
state: Shanxi
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shanxi
city: Xi'an
country: China
facility: Xi'an Gaoxin Hospital
state: Shanxi
city: Xianyang
country: China
facility: Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine
state: Shanxi
city: Xianyang
country: China
facility: Xianyang first people's hospital
state: Shanxi
city: Xianyang
country: China
facility: Xianyang Hospital of Yan 'an University
state: Shanxi
city: Chengdu
country: China
facility: The Fifth People's Hospital of Chengdu
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Dali
country: China
facility: The First Affiliated Hospital of Dali University
state: Yunnan
city: Kunming
country: China
facility: Fuwai Yunnan Cardiovascular Hospital
state: Yunnan
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital , Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hanzhou
country: China
facility: Affiliated Hospital of Hangzhou Normal University
state: Zhejiang
city: Hanzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Jiaxing
country: China
facility: Jiaxing First Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Huamei Hospital, University of Chinese Academy of Sciences (Ningbo Second Hospital)
state: Zhejiang
city: Ningbo
country: China
facility: The First Hospital of Ningbo
state: Zhejiang
city: Wenzhou
country: China
facility: First affiliated hospital of Wenzhou medical university
state: Zhejiang
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jian Zhang, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chao Yang Hospital
name: Mulei Chen, M.D
role: PRINCIPAL_INVESTIGATOR
References: