A Phase I/II Clinical Trial of Intramyocardial Injection of HucMSCs for the Treatment of Chronic Heart Failure

Official title

A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of Intramyocardial Injection of Human Umbilical Cord Mesenchymal Stem Cells (HucMSCs) Combined With Coronary Artery Bypass Grafting in the Treatment of Chronic Heart Failure Caused by Chronic Ischemic Cardiomyopathy

Overview

B2278 is a human umbilical cord mesenchymal stem cell (HucMSCs) injection derived from the umbilical cord. It has the advantages of stronger immune regulation, stronger expansion capacity, lower immunogenicity, and greater accessibility. The preliminary research results indicated that the B2278 injection promote the polarization of macrophages towards a reparative state through paracrine action, directly promote angiogenesis and inhibited inflammatory responses, thereby exerting effects on myocardial repair and treatment of heart failure, and it is also safe and well-tolerated. This trial is a multi-center I/II phase clinical trial of the human umbilical cord mesenchymal stem cell injection solution, aiming to explore the dosage and regimen for the intramyocardial injection of B2278 in combination with coronary artery bypass grafting surgery for the treatment of chronic heart failure caused by chronic ischemic cardiomyopathy, and to evaluate the safety, tolerance and efficacy of allogeneic intramyocardial injection of the human umbilical cord mesenchymal stem cell injection solution in patients with chronic ischemic heart failure.

Interventions

• Drug Mesenchymal stem cells(HucMSCs)
  B2278 is mesenchymal stem cells derived from human umbilical cord.
• Procedure CABG
  only CABG

Primary outcome measures

• In phase I, primary outcome will be measured with safety events including DLT, AE, SAE, TEAE, and MACE. In phase II, primary outcome will be measured with the change in LVEF based on CMR detection after 6 months of administration. [Time frame: 6 months]

Secondary outcome measures (9)

• The changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) on CMR compared to the baseline. [Time frame: 6 months]
• The changes from baseline of LVEF, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), LVEDV, LVESV on UCG [Time frame: 28 days, 3 months and 6 months]
• The proportion of participants with improved LVEF (the proportion of participants whose LVEF increased by ≥10% compared to the baseline and whose LVEF was >40% based on CMR and/or UCG); [Time frame: 3 months and 6 months]
• The distribution of the New York Heart Association (NYHA) cardiac function classification [Time frame: 28 days, 3 months and 6 months]
• The proportion of participants with NYHA classification ≤ II level [Time frame: 28 days, 3months and 6months]
• The changes in the 6-minute walk test (6MWT) results compared to the baseline [Time frame: 28 days, 3 months and 6months]
• The changes in the Minnesota Heart Failure Quality of Life Questionnaire (MLHFQ) from the baseline [Time frame: 28 days, 3months and 6months]
• The change in the result of amino-terminal pro-brain natriuretic peptide (NT-proBNP) compared to the baseline [Time frame: 28 days, 3months and 6months]
• The proportion of participants whose heart failure worsened (requiring hospitalization or emergency treatment due to the aggravation of heart failure symptoms and signs) [Time frame: 3 months and 6months]

Eligibility criteria

Inclusion criteria

• 1\) Age from 18 to 80 years, both genders are eligible ;
• 2\) Clinically judged to be suitable for CABG treatment due to chronic ischemic cardiomyopathy;
• 3\) LVEF (left ventricular ejection fraction) is ≤ 40% as indicated by echocardiography (modified Simpson method) or cardiac magnetic resonance (CMR);
• 4\) NYHA (New York Heart Association) cardiac function classification of grade II-IV;
• 5\) Patients or their legal guardians agreed to participate in this trial and signed the informed consent form.

Major exclusion Criteria:

• 1\) Severe left ventricular dysfunction, with LVEF ≤ 20% (based on the UCG or CMR examination results during the screening period);
• 2\) Non-ischemic chronic left heart dysfunction, including but not limited to acute left heart dysfunction, dilated cardiomyopathy, severe right heart dysfunction (such as bilateral lower extremity edema accompanied by jugular vein distension, liver enlargement, etc.) or severe pulmonary hypertension (PASP > 70 mmHg);
• 3\) Clinically determined that other surgical procedures need to be performed simultaneously during CABG surgery, including but not limited to congenital heart disease requiring concurrent surgical intervention, heart valve disease, ventricular aneurysm, ventricular septal perforation, papillary muscle dysfunction, aortic dissection, intracardiac mass, thrombus or neoplasm；
• 4\) Acute ST-segment elevation myocardial infarction or stroke event within 1 month before enrollment；
• 5\) Uncontrolled malignant arrhythmia;
• 6)have undergone or are awaiting heart transplantation or implantation of a left ventricular assist device (LVAD).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai
• Changhai Hospital — Shanghai
• Shanghai Chest Hospital — Shanghai
• Shanghai General Hospital — Shanghai

Identifiers

NCT: NCT07265349 · TASLY-BM-B2278-HF-I/Ⅱ

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗