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Autologous Induced Pluripotent Stem Cells of Cardiac Lineage for Congenital Heart Disease

Primary Purpose

Univentricular Heart, Congenital Heart Disease, Heart Failure NYHA Class III

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
iPSC-CL
Sponsored by
HeartWorks, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Univentricular Heart focused on measuring univentricular, heart disease, iPSC, induced pluripotent stem cell

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

Individuals may be considered eligible for enrollment for Part I of this study (Skin Punch Biopsy) if in the best judgment of the Principal Investigator they will meet eligibility criteria outlined below at the time it is determined acceptable investigational product is available for administration (approximately 9 months post skin punch biopsy). Inclusion and exclusion criteria apply to both the treatment and control arms of the study unless otherwise specified. Inclusion Criteria Individuals who meet all the following criteria are eligible for enrollment as study participants: Age 18 to 40 years old Subject must be able to understand and provide informed consent. Univentricular congenital heart disease. End-stage systolic heart failure, defined as Class IV according to New York Heart Association (NYHA) with abnormal visually estimated ejection fraction below 40%. Prognosis of 1 to 1.5 years survival at time of skin biopsy. The patient falls into one of the following categories: Currently listed for heart transplantation at an accredited program in the US but has an expected waiting time for a suitable organ that is likely longer than anticipated life-expectancy. Has been denied access to a heart transplantation at an accredited US institution. Is currently on or planning to be on mechanical support as destination therapy. All guideline directed therapy available to the subject has been maximized, for a minimum of 3 months prior to enrollment. Adequate social support system that facilitates subject participation in all study required tests and procedures and supports the subject's ability to comply with long-term study requirements. Exclusion Criteria Individuals who meet any of the following criteria are not eligible for enrollment as study participants: No available autologous iPSC-CL as defined by the manufacturer's release criteria. (This applies to Part II of the study and applies to the treatment arm only.) History of symptomatic episodes of cardiac arrythmia requiring cardiac defibrillation or escalation of medications. Heart failure with preserved ejection fraction. Heart failure due to co-morbid conditions (e.g., amyloidosis, valvular heart disease, refractory anemia). QTc greater than 500 ms. Stage III or higher chronic kidney disease. History of liver cirrhosis. History of coronary artery disease. Uncontrolled diabetes mellitus. Any history of cancer. Contraindication for use of amiodarone for up to 3 months (treatment arm only). Contraindication for insertion of Insertable Cardiac Monitor. Contraindication for placement of LifeVest cardioverter defibrillator. Positive serology testing for HIV, Hepatitis B, Hepatitis C or Syphilis. Obesity with BMI greater than 30. Current alcohol or drug abuse precluding heart transplantation. Active infection requiring ongoing treatment. Contraindication to anesthesia. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality of the data obtained from the study. Inability or unwillingness of a participant to give written informed consent or comply with study protocol. History of non-compliance. Inability to be accompanied around the clock for any part of the first 3 weeks post product administration. Uncontrolled depression. Denied heart transplant due to social determinants. Current participation in another cardiac interventional clinical trial that could confound the results of this study. Previous heart transplant.

Sites / Locations

  • Mayo ClinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treated

Control

Arm Description

Subjects in Treated arm will receive one dose of Investigational Product. Within this arm are three dose levels. Dose level selection will be determined by product availability subjects have available product and when they can be treated. Dose levels will escalate in order of treatment date.

Subjects who enroll but do not receive Investigational Product will be placed in the control arm.

Outcomes

Primary Outcome Measures

Short term safety
The primary safety endpoint is short term safety defined as the rate of new or worsening serious adverse events (SAE) from any System Organ Class (SOC) within 3 months of the iPSC-CL delivery as compared to the control arm.
Feasibility
The primary feasibility endpoint is the percentage of individuals with collected skin cells that meet all iPSC-CL release criteria and the percentage of individuals that have cells delivered.

Secondary Outcome Measures

Long term safety
Long term safety measured as new or worsening serious adverse events for two years after iPSC-CL delivery as compared to the control arm.
Cardiac High Sensitivity Troponin T
Change from baseline in Cardiac High Sensitivity Troponin T at 3 hours (±30 min) and 6 hours (±30 min) after iPSC-CL delivery and at 1 month post-surgery as compared to the control arm.
NT-pro-BNP
Change from baseline in NT-pro-BNP levels at 1 and 3 months post iPSC-CL delivery as compared to the control arm.
Tumor marker levels
Change from baseline in tumor marker levels (PSA (males only), CA 125, CEA, CA 19-9, alpha-fetoprotein (AFP), CA 195, Alpha Subunit HCG) 3 months and annually after iPSC-CL delivery as compared to the control arm.
Panel Reactive Antibody (PRA) levels
Change from baseline in Panel Reactive Antibody (PRA) levels at 3 and 12 months post-iPSC-CL delivery as compared to the control arm.

Full Information

First Posted
November 30, 2022
Last Updated
September 20, 2023
Sponsor
HeartWorks, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05647213
Brief Title
Autologous Induced Pluripotent Stem Cells of Cardiac Lineage for Congenital Heart Disease
Official Title
Safety and Feasibility of Autologous Induced Pluripotent Stem Cells of Cardiac Lineage in Subjects With Congenital Heart Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 3, 2023 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
February 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HeartWorks, Inc.

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
The goal of this clinical trial is to test the safety of lab-grown heart cells made from stem cells in subjects with congenital heart disease. The main questions it aims to answer are: Is this product safe to deliver to humans Is the conduct of this trial feasible Participants will be asked to: Agree to testing and monitoring before and after product administration Receive investigational product Agree to lifelong follow-up Researchers will compare subjects from the same pool to see if there is a difference between treated and untreated subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Univentricular Heart, Congenital Heart Disease, Heart Failure NYHA Class III, Heart Failure NYHA Class IV
Keywords
univentricular, heart disease, iPSC, induced pluripotent stem cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treated
Arm Type
Experimental
Arm Description
Subjects in Treated arm will receive one dose of Investigational Product. Within this arm are three dose levels. Dose level selection will be determined by product availability subjects have available product and when they can be treated. Dose levels will escalate in order of treatment date.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Subjects who enroll but do not receive Investigational Product will be placed in the control arm.
Intervention Type
Biological
Intervention Name(s)
iPSC-CL
Intervention Description
Autologous IPSCL
Primary Outcome Measure Information:
Title
Short term safety
Description
The primary safety endpoint is short term safety defined as the rate of new or worsening serious adverse events (SAE) from any System Organ Class (SOC) within 3 months of the iPSC-CL delivery as compared to the control arm.
Time Frame
3 months
Title
Feasibility
Description
The primary feasibility endpoint is the percentage of individuals with collected skin cells that meet all iPSC-CL release criteria and the percentage of individuals that have cells delivered.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Long term safety
Description
Long term safety measured as new or worsening serious adverse events for two years after iPSC-CL delivery as compared to the control arm.
Time Frame
2 years
Title
Cardiac High Sensitivity Troponin T
Description
Change from baseline in Cardiac High Sensitivity Troponin T at 3 hours (±30 min) and 6 hours (±30 min) after iPSC-CL delivery and at 1 month post-surgery as compared to the control arm.
Time Frame
1 month
Title
NT-pro-BNP
Description
Change from baseline in NT-pro-BNP levels at 1 and 3 months post iPSC-CL delivery as compared to the control arm.
Time Frame
3 months
Title
Tumor marker levels
Description
Change from baseline in tumor marker levels (PSA (males only), CA 125, CEA, CA 19-9, alpha-fetoprotein (AFP), CA 195, Alpha Subunit HCG) 3 months and annually after iPSC-CL delivery as compared to the control arm.
Time Frame
Three months from date of treatment and every 12 months after treatment, assessed up to 15 years
Title
Panel Reactive Antibody (PRA) levels
Description
Change from baseline in Panel Reactive Antibody (PRA) levels at 3 and 12 months post-iPSC-CL delivery as compared to the control arm.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Individuals may be considered eligible for enrollment for Part I of this study (Skin Punch Biopsy) if in the best judgment of the Principal Investigator they will meet eligibility criteria outlined below at the time it is determined acceptable investigational product is available for administration (approximately 9 months post skin punch biopsy). Inclusion and exclusion criteria apply to both the treatment and control arms of the study unless otherwise specified. Inclusion Criteria Individuals who meet all the following criteria are eligible for enrollment as study participants: Age 18 to 40 years old Subject must be able to understand and provide informed consent. Univentricular congenital heart disease. End-stage systolic heart failure, defined as Class IV according to New York Heart Association (NYHA) with abnormal visually estimated ejection fraction below 40%. Prognosis of 1 to 1.5 years survival at time of skin biopsy. The patient falls into one of the following categories: Currently listed for heart transplantation at an accredited program in the US but has an expected waiting time for a suitable organ that is likely longer than anticipated life-expectancy. Has been denied access to a heart transplantation at an accredited US institution. Is currently on or planning to be on mechanical support as destination therapy. All guideline directed therapy available to the subject has been maximized, for a minimum of 3 months prior to enrollment. Adequate social support system that facilitates subject participation in all study required tests and procedures and supports the subject's ability to comply with long-term study requirements. Exclusion Criteria Individuals who meet any of the following criteria are not eligible for enrollment as study participants: No available autologous iPSC-CL as defined by the manufacturer's release criteria. (This applies to Part II of the study and applies to the treatment arm only.) History of symptomatic episodes of cardiac arrythmia requiring cardiac defibrillation or escalation of medications. Heart failure with preserved ejection fraction. Heart failure due to co-morbid conditions (e.g., amyloidosis, valvular heart disease, refractory anemia). QTc greater than 500 ms. Stage III or higher chronic kidney disease. History of liver cirrhosis. History of coronary artery disease. Uncontrolled diabetes mellitus. Any history of cancer. Contraindication for use of amiodarone for up to 3 months (treatment arm only). Contraindication for insertion of Insertable Cardiac Monitor. Contraindication for placement of LifeVest cardioverter defibrillator. Positive serology testing for HIV, Hepatitis B, Hepatitis C or Syphilis. Obesity with BMI greater than 30. Current alcohol or drug abuse precluding heart transplantation. Active infection requiring ongoing treatment. Contraindication to anesthesia. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality of the data obtained from the study. Inability or unwillingness of a participant to give written informed consent or comply with study protocol. History of non-compliance. Inability to be accompanied around the clock for any part of the first 3 weeks post product administration. Uncontrolled depression. Denied heart transplant due to social determinants. Current participation in another cardiac interventional clinical trial that could confound the results of this study. Previous heart transplant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clint Hagen, M.S.
Phone
1-(507) 577-1764
Email
clint@webuildhearts.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy J Nelson, M.D., Ph.D.
Organizational Affiliation
HeartWorks, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55901
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Miller
Email
HLHS@mayo.edu
First Name & Middle Initial & Last Name & Degree
Lori Riess
Email
HLHS@mayo.edu
First Name & Middle Initial & Last Name & Degree
Rebecca K Ameduri, M.D.

12. IPD Sharing Statement

Learn more about this trial

Autologous Induced Pluripotent Stem Cells of Cardiac Lineage for Congenital Heart Disease

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