Human Embryonic Stem Cell-Derived Cardiomyocyte Therapy for Chronic Ischemic Left Ventricular Dysfunction (HECTOR)
Primary Purpose
Chronic Ischemic Left Ventricular Dysfunction
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Human Embryonic Stem Cell-Derived Cardiomyocyte 50M cells
Human Embryonic Stem Cell-Derived Cardiomyocyte 150 cells
Human Embryonic Stem Cell-Derived Cardiomyocyte 300M cells
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Ischemic Left Ventricular Dysfunction
Eligibility Criteria
Inclusion Criteria:
- Be ≥ 21 and < 80 years of age.
- Provide written informed consent.
- Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to MI as defined by previous myocardial infarction documented by an imaging study demonstrating coronary artery disease with corresponding areas of akinesis, dyskinesis, or severe hypokinesis.
- Be a candidate for cardiac catheterization within 5 to 10 weeks of screening.
- Have been treated with appropriate maximal medical therapy for heart failure or postinfarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensinconverting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs) or have appropriate medical indication precluding use of one or both of these agents, the patient must have been on a stable dose of a clinically appropriate agent for 1 month or within no more than doubling the dose of any of ARB, ACE inhibitors, and ARNIs over the last 3 months.
- Left ventricular ejection fraction below 40%.
- Class II/III NYHA symptoms of heart failure within the 6 months prior to baseline testing.
- Hospitalization in the past 6 months or NT pro-BNP > 1200 pg/mL, or >1600 pg/mL if atrial fibrillation was present.
- Automated implantable cardioverter-defibrillator (AICD) in place.
Exclusion Criteria:
- Have a baseline glomerular filtration rate < 35 ml/min/1.73 m2
- Have a known, serious radiographic contrast allergy.
- Have a prosthetic aortic valve or heart constrictive device.
- Have a documented presence of aortic stenosis (aortic stenosis graded as 1.5 cm2 or less).
- Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
- Have evidence of a life-threatening arrhythmia in the absence of a defibrillator (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete second- or third-degree heart block in the absence of a functioning pacemaker) or QTc interval > 550 ms on screening ECG.
- AICD firing in the past 60 days prior to enrollment.
- Be eligible for or require coronary artery revascularization.
- Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/µl, or platelet values < 100,000/µl without another explanation.
- Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
- Have a coagulopathy (INR > 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR < 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment.
- Have known allergies to penicillin or streptomycin.
- Be an organ transplant recipient.
- Have a history of organ or cell transplant rejection.
- Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease-free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
- Have a non-cardiac condition that limits lifespan to < 1 year.
- Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists.
- Be serum-positive for HIV, hepatitis BsAg, or viremic hepatitis C.
- Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
- Be a female patient who is pregnant, nursing, or have child-bearing potential but is not using effective birth control.
- Tested positive for SARS-CoV-2 within the last 30 days
Sites / Locations
- Stanford Hospital and ClinicsRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm Description
Low dose (50M cells)
Medium dose (150M cells)
High dose (300M cells)
Outcomes
Primary Outcome Measures
The maximum tolerated dose (MTD) among 3 dose levels of allogeneic human embryonic stem cell-derived cardiomyocytes (hESC-CMs)
The primary endpoints are safety and feasibility. The feasibility of preparing and delivering the study product, as well as collecting cardiac MRI variables in subjects will be assessed.
Secondary Outcome Measures
Full Information
NCT ID
NCT05068674
First Posted
September 24, 2021
Last Updated
September 15, 2022
Sponsor
Joseph C. Wu
Collaborators
California Institute for Regenerative Medicine (CIRM)
1. Study Identification
Unique Protocol Identification Number
NCT05068674
Brief Title
Human Embryonic Stem Cell-Derived Cardiomyocyte Therapy for Chronic Ischemic Left Ventricular Dysfunction
Acronym
HECTOR
Official Title
A Phase I, Randomized Pilot Study of Human Embryonic Stem Cell-Derived Cardiomyocytes (hESC-CMs) in PaTients With ChrOnic Ischemic Left VentRicular Dysfunction Secondary to Myocardial Infarction (HECTOR)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2022 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joseph C. Wu
Collaborators
California Institute for Regenerative Medicine (CIRM)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This clinical study will utilize a new cell therapy approach (Human embryonic stem cells derived cardiomyocytes or hESC-CMs) to improve survival and cardiac function in patients with chronic left ventricular dysfunction secondary to MI (Myocardial Infarction).
Detailed Description
The phase I dose-escalation pilot study is intended as an initial safety assessment to establish the MTD prior to the phase II randomized, double-blinded, placebo-controlled study. An estimated eighteen (18) patients in phase I who are scheduled to undergo cardiac catheterization and have met all inclusion/exclusion criteria will be enrolled.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Ischemic Left Ventricular Dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Phase I will be a standard 3+3 dose-escalation study to evaluate 3 doses of allogeneic hESC-CMs
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Active Comparator
Arm Description
Low dose (50M cells)
Arm Title
Cohort 2
Arm Type
Active Comparator
Arm Description
Medium dose (150M cells)
Arm Title
Cohort 3
Arm Type
Active Comparator
Arm Description
High dose (300M cells)
Intervention Type
Drug
Intervention Name(s)
Human Embryonic Stem Cell-Derived Cardiomyocyte 50M cells
Other Intervention Name(s)
Human ESC-CMs
Intervention Description
50 million (M) cells delivered in a dose of 5M cells per injection over 10 injections.
Intervention Type
Drug
Intervention Name(s)
Human Embryonic Stem Cell-Derived Cardiomyocyte 150 cells
Other Intervention Name(s)
Human ESC-CMs
Intervention Description
150M cells delivered in a dose of 15M cells per injection over 10 injections
Intervention Type
Drug
Intervention Name(s)
Human Embryonic Stem Cell-Derived Cardiomyocyte 300M cells
Other Intervention Name(s)
Human ESC-CMs
Intervention Description
300M cells delivered in a dose of 30M per injection over 10 injections
Primary Outcome Measure Information:
Title
The maximum tolerated dose (MTD) among 3 dose levels of allogeneic human embryonic stem cell-derived cardiomyocytes (hESC-CMs)
Description
The primary endpoints are safety and feasibility. The feasibility of preparing and delivering the study product, as well as collecting cardiac MRI variables in subjects will be assessed.
Time Frame
3 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be ≥ 21 and < 80 years of age.
Provide written informed consent.
Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to MI as defined by previous myocardial infarction documented by an imaging study demonstrating coronary artery disease with corresponding areas of akinesis, dyskinesis, or severe hypokinesis.
Be a candidate for cardiac catheterization within 5 to 10 weeks of screening.
Have been treated with appropriate maximal medical therapy for heart failure or postinfarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensinconverting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs) or have appropriate medical indication precluding use of one or both of these agents, the patient must have been on a stable dose of a clinically appropriate agent for 1 month or within no more than doubling the dose of any of ARB, ACE inhibitors, and ARNIs over the last 3 months.
Left ventricular ejection fraction below 40%.
Class II/III NYHA symptoms of heart failure within the 6 months prior to baseline testing.
Hospitalization in the past 6 months or NT pro-BNP > 1200 pg/mL, or >1600 pg/mL if atrial fibrillation was present.
Automated implantable cardioverter-defibrillator (AICD) in place.
Exclusion Criteria:
Have a baseline glomerular filtration rate < 35 ml/min/1.73 m2
Have a known, serious radiographic contrast allergy.
Have a prosthetic aortic valve or heart constrictive device.
Have a documented presence of aortic stenosis (aortic stenosis graded as 1.5 cm2 or less).
Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
Have evidence of a life-threatening arrhythmia in the absence of a defibrillator (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete second- or third-degree heart block in the absence of a functioning pacemaker) or QTc interval > 550 ms on screening ECG.
AICD firing in the past 60 days prior to enrollment.
Be eligible for or require coronary artery revascularization.
Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/µl, or platelet values < 100,000/µl without another explanation.
Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
Have a coagulopathy (INR > 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR < 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment.
Have known allergies to penicillin or streptomycin.
Be an organ transplant recipient.
Have a history of organ or cell transplant rejection.
Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease-free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
Have a non-cardiac condition that limits lifespan to < 1 year.
Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists.
Be serum-positive for HIV, hepatitis BsAg, or viremic hepatitis C.
Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
Be a female patient who is pregnant, nursing, or have child-bearing potential but is not using effective birth control.
Tested positive for SARS-CoV-2 within the last 30 days
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joseph C. Wu, MD, PhD
Phone
(650) 736-2246
Email
joewu@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Evgenios Neofytou, MD
Phone
(650) 736-2246
Email
neofytou@stanford.edu
Facility Information:
Facility Name
Stanford Hospital and Clinics
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Human Embryonic Stem Cell-Derived Cardiomyocyte Therapy for Chronic Ischemic Left Ventricular Dysfunction
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