Clinical trial NCT04907526: Intramyocardial Injection of Autologous UCB-MNC During Fontan Surgery for SRV Dependent CHD
Official title: Phase I Study of Intramyocardial Injection of Autologous Umbilical Cord Blood-Derived Mononuclear Cells During Fontan Surgical Palliation of Single Right Ventricle-Dependent Congenital Heart Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Congenital Heart Disease, SRV Dependent
Keywords: Hypoplastic Left Heart Syndrome
HLHS
Congenital Heart Disease
Umbilical Cord Blood
UCB
Cord Blood
Stem Cells
Regenerative therapy
Stage III Fontan
Fontan surgery
Lead sponsor: ReGen Theranostics, Inc.
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: University of Oklahoma
name: Children's Hospital of Philadelphia
name: Children's Hospital Los Angeles
name: Children's Hospitals and Clinics of Minnesota
name: Children's Hospital Colorado
name: Ochsner Health System
name: Children's of Alabama
name: Children's Hospital Medical Center, Cincinnati
name: The Hospital for Sick Children
First posted: 2021-05-28
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers want to better understand what happens to the heart when the autologous (from one's own body) stem cells are injected directly into muscle of the right side of the heart during the Fontan (Stage III) surgery. They want to see if there are changes in the electrical activity, the structure, and the function of the heart following this stem cell-based therapy. Researchers will compare the results from people who receive the stem cells to the results from people who do not receive the stem cells.

Detailed description: This Phase I study is a multicenter, prospective, open-label, non-randomized study designed to evaluate the safety, of autologous UCB-MNC delivered into the right ventricular myocardium of subjects with severe CHD defined by single right ventricular dependent circulatory systems at the time of a planned Fontan surgical palliation. This will be achieved by comparing the data collected in the treatment arm to the equivalent data collected in the control arm. The purpose of this non-randomized open-label Phase I clinical study is to prospectively evaluate the safety, as measured by the short-term and long-term safety endpoints and change in baseline comparatives, for the autologous UCB-MNC intramyocardial injections into the single, morphologically right ventricle of subjects with severe CHD requiring Fontan surgical palliation. The treatment group will be compared to an untreated control group.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of a congenital hear defect with functionally single right ventricle (such as HLHS, HLHS variants, unbalanced AV septal defect with R dominance, DORV with Hypoplastic LV) undergoing Fontan surgical palliation
* At least 2 and less than or equal to 5 years of age at time of Fontan surgical palliation
* For subjects enrolling in the treatment arm, previous participation in clinical trial Umbilical Cord Blood Collection and Processing for Hypoplastic Left Heart Syndrome patients (NCT01856049) with autologous UCB-MNC product collected and available for distribution is required.

Exclusion Criteria:

* History of DMSO reaction (treatment arm only subjects).
* Parent(s) or legal guardian unwilling to have their child participate or unwilling to follow the study procedures.
* Severe chronic diseases at the discretion of the treating physician.
* Extensive extra-cardiac syndromic features.
* History of cancer.
* Any of the following complications of his/her congenital heart disease:

  * any condition requiring urgent, or unplanned intervention procedure within 15 days prior to Fontan surgical palliation, unless complete and full cardiac recovery is documented by site investigator.
  * severe pulmonary hypertension (reported in the medical record as \>70% systemic pressure)
  * Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome, not directly related tot he stem cell product or its injection procedure, during or after Fontan surgical palliation.
* Individuals with severe heart failure that requires heart transplantation
* Individuals with refractory or worsening arrhythmia
* Individuals with an automated implantable cardioverter defibrillator (AICD) or pacemaker
* Patient with prior surgical complications during the Fontan surgical palliation that resulted in or could be reasonably expected to significantly decrease cardiac function

Primary outcomes:
measure: Short-term safety
timeFrame: Within 3 months post Fontan surgery
Secondary outcomes:
measure: Long term safety
timeFrame: Within 2 years post Fontan surgery
measure: Right ventricular function
timeFrame: Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery
measure: High sensitivity Troponin T
timeFrame: 3 hours post enrollment, 6 hours post enrollment, hospital discharge (up to 30 days post Fontan surgery)
measure: NT-pro-BNP
timeFrame: Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery
measure: Panel Reactive Antibody
timeFrame: Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery
measure: Weight
timeFrame: Baseline, 3 months post-Fontan surgery, 12 months post-Fontan surgery
measure: Cumulative days hospitalization
timeFrame: 3 months post discharge, 12 months post discharge
measure: PROMIS Parent Proxy Scale v1.0-Global Health 7
timeFrame: Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months, 12 months, 18 months, 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Medical Center
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Oklahoma City
country: United States
facility: University of Oklahoma Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Mayo Clinic
name: Joseph Dearani
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Oklahoma University Medical Center
name: Harold M Burkhart
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Joseph w Rossano
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Minnesota
name: David M Overman
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Los Angeles
name: Ram Kumar Subramanyan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Colorado
name: James Jaggers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ochsner Health System
name: Benjamin Peeler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemer Carlo, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: James Tweddell, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital forSick Children
name: Jason Maynes, MD
role: PRINCIPAL_INVESTIGATOR
References: