Clinical trial NCT04982081: Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
Official title: Treating Congestive Heart Failure Patients With Human iPSC-derived Cardiomyocytes Through Catheter-based Endocardial Injection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Cardiovascular Diseases
Congestive Heart Failure
Dilated Cardiomyopathy
Keywords: induced pluripotent stem cell
Congestive heart failure
Regenerative medicine
dilated cardiomyopathy
Lead sponsor: Help Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Xijing Hospital
First posted: 2021-07-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Heart failure is the primary cause of morbidity and mortality worldwide. Currently drug treatments for heart failure manage the symptoms, but not restore the loss cardiomyocytes due to the very limited regenerative capability in the adult heart. Novel reparative therapies that replace the cardiomyocytes loss are highly demanded to restore the cardiac function. The main purposes of this explanatory study is to investigate the safety and efficacy of the catheter-based endocardial delivery of human iPSC-derived cardiomyocytes in patients with congestive heart failure.

Detailed description: Patients with severe congestive heart failure will be treated with allogeneic human iPSC-derived cardiomyocytes (HiCM-188) through the catheter-based injections. HiCM188, produced by Help therapeutics with cGMP condition, will be transplanted into the myocardium through a transcatheter endocardial injection system with two dosage (100 million cells or 400 million cells). The safety and efficacy assessments will be conducted at1, 3, 6 and 12 months after the cell transplantation.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18-75 years (including 18 and 75).
2. Signed the informed consent.
3. Patients with congestive heart failure who have received regular treatment for heart failure.
4. New York Heart Association (NYHA) Class III or IV despite optimal standard of care
5. Left Ventricular Ejection Fraction (LVEF)\<40% as assessed by echocardiography ( measure in the 3 months of recruit is included, excluding the measured values within 1 month of myocardial infarction ）
6. The thickness of left ventricular ≥8mm
7. Female patient who is not pregnant or nursing during the clinical trial

Exclusion Criteria:

1. PRA ≥ 20% or DSA positive.
2. Patients received treatments such as pacemakers, ICD or CRT device.
3. Patient with severe valvular disease or presence of a mechanical valve replacement, such as PCI implantation, or patients requiring simultaneous radiofrequency ablation of atrial fibrillation.
4. Patient with any therapeutic traumatic heart surgery within 30 days.
5. Hemodynamic instability or cardiogenic shock.
6. Right heart failure.
7. Restrictive cardiomyopathy such as amyloidosis, sarcoidosis or hematochromia, constrictive pericarditis.
8. Myocardial infarction occurred within 30 days or stroke occurred within 60 days before enrollment.
9. Thickness at left ventricular free wall infarction \< 6 mm.
10. Severe ventricular arrhythmias (persistent ventricular tachycardia or other conditions that the investigator considers necessary to exclude).
11. Baseline glomerular filtration rate \< 30 ml/min / 1.73 m2.
12. Abnormal liver function: ALT or AST 3 times higher than the normal value.
13. Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cells count \<2,500/ul or platelet count \<100000 / ul.
14. Known allergies to penicillin, streptomycin or radiocontrast agent.
15. Abnormal coagulation function, INR \> 1.3, which cannot be corrected.
16. Contra-indication to performance of a magnetic resonance imaging scan and PET/ECT examinations.
17. Organ transplant recipient
18. Patients with other malignant disease within 5 years prior to enrollment.
19. Non-cardiac condition that limits lifespan to \< 1 year
20. On chronic therapy with immunosuppressant medication such as glucocorticoid or TNFα antagonist
21. Contra-indication to take immunosuppressant medication.
22. Serum positive for infectious diseases (HIV, HBV, HCV, TP).
23. Participated in other clinical trials within the previous 3 months .
24. Female patient who is pregnant or nursing.
25. Other condition that the investigator considers inappropriate for participation in the study.

Primary outcomes:
measure: Incidence of major serious adverse events (SAEs)
timeFrame: First month post-catheterization
Secondary outcomes:
measure: Incidence of severe arrhythmia
timeFrame: 1-6 months post-catheterization
measure: Incidence of newly formed tumors
timeFrame: Baseline, 1,3,6 and 12 months post-catheterization
measure: Changes in penal reactive antibodies (PRA)
timeFrame: Baseline, 1, 3 and 6 months post-catheterization
measure: Changes in donor specific antibodies (DSA)
timeFrame: Baseline, 1, 3 and 6 months post-catheterization
measure: Overall Left Ventricular systolic performance as assessed by MRI
timeFrame: Baseline, 1, 3, 6 and 12 months post-catheterization
measure: Overall Left Ventricular systolic performance as assessed by PET/ECT Scan
timeFrame: Baseline, 6 and 12 months post-catheterization
measure: Functional status by 6 minute walk test
timeFrame: Baseline, 1,3,6 and 12 months post-catheterization
measure: Functional status by New York Heart Association (NYHA) Classification
timeFrame: Baseline, 1,3,6 and 12 months post-catheterization
measure: Minnesota Living With Heart Failure Questionnaire (MLHFQ)
timeFrame: Baseline, 1,3,6 and 12 months post-catheterization
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Help Therapeutics
state: Jiangsu
Study officials:
affiliation: Xijing Hospital
name: Ling Tao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: