Study of Intramyocardial Injection of Ventrix Bio Extracellular Matrix (VentriGel) to Assess the Safety and Feasibility in Pediatric Patients with Hypoplastic Left Heart Syndrome (HLHS)

The goal of this Phase I Open-Label study is to demonstrate the safety and feasibility of VentriGel injection in children with Hypoplastic Left Heart Syndrome (HLHS).

The main questions it aims to answer are:

• Whether VentriGel is safe in treating patients with HLHS
• Whether there are any preliminary improvements in measures of cardiac function following Ventrigel injection

Study Overview

• Status: Not yet recruiting
• Conditions: Hypoplastic Left Heart Syndrome
• Intervention / Treatment: Drug: Ventrix Bio Extracellular Matrix

Detailed Description

HLHS, a type of congenital heart disease, presents a unique challenge where the left ventricle fails to develop, necessitating the right ventricle to manage both systemic and pulmonary blood flow. This condition, once fatal, has become manageable due to advancements in surgical techniques, with reported 5-year survival rates of 70-90%. However, these staged procedures, while lifesaving, can strain the right ventricle, leading to long-term issues such as weakened muscle and reduced cardiac function. Additionally, even with surgical intervention, patients often face a diminished quality of life.

Addressing these challenges, ongoing clinical trials explore regenerative therapies, particularly stem cell injections, aiming to improve heart function. Yet, concerns persist regarding the practicality and efficacy of these treatments, including issues with cell survival and coordination of injections within narrow timeframes.

Innovatively, the investigator and the team propose an alternative approach using VentriGel, an injectable hydrogel derived from decellularized porcine myocardium. Originally designed for treating heart failure post-myocardial infarction in adults, VentriGel has shown promising results in animal models, demonstrating significant improvements in cardiac function. Notably, its shelf-stable nature and flexible timing for administration offer advantages over traditional stem cell therapies.

Moreover, VentriGel's effectiveness in addressing right-ventricular failure, as demonstrated in recent studies, highlights its potential as a solution for HLHS patients. Leveraging approved extracellular matrix devices, such as Alloderm and SurgiSIS, further underscores the feasibility and safety of this approach, paving the way for potentially transformative treatments in congenital heart diseases.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: William Mahle, MD; Phone Number: 404-256-2593; Email: MahleW@kidsheart.com

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Altanta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with Hypoplastic Left Heart Syndrome (HLHS) requiring Stage II Glenn operation under one year of age

Exclusion Criteria:

• Subjects undergoing the Stage II Glenn operations who do not have HLHS
• Subjects requiring mechanical circulatory support within 5 days pre pre-surgical intervention
• Parent or guardian unwilling or unable to comply with necessary follow-up(s)
• Immunosuppressive diseases or subjects who require treatment with interventions that cause immunosuppression
• A history of tumor or malignancy
• Coagulation disorders
• Chromosomal abnormalities that limit expected survival to < 1 year
• Abnormal lab values that may increase the risk of the study procedure (WBC >20,000 cells/ul or < 1,000 cells/ul; platelet count < 50,000 cells/ul; Hgb < 8.0 gm/dl; LFTs > 2x reference lab upper limit of normal) at the time of screening
• Subjects with conduction abnormalities, including atrioventricular block and bundle branch blocks
• Ventricular arrhythmias due to antiarrhythmic pharmacological therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ventrix Bio Extracellular Matrix; Treatment intervention of a total of 8 injections into the right ventricle of the heart will occur before the patient comes off of the heart-lung bypass machine used during the Stage II Glenn Operation. The treatment will be conducted according to clinical guidelines set in place while the patient is undergoing a surgical intervention before the patient comes off the heart/lung bypass machine required for the stage II Glenn Procedure.

Drug: Ventrix Bio Extracellular Matrix; VentriGel will be administered by injection into the right ventricle of the heart in the following defined doses per injection. There will be a total of 8 injections. The proposed dose of up to 0.6 mL is administered as up to 8 sequential injections of 4 injections of 0.1 mL each and 4 injections of 0.05 mL each.; Other Names: VentriGel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ventricular tachycardia events	Number of sustained/symptomatic ventricular tachycardia incidences requiring intervention with inotropic support or anti-arrhythmics	upto 30 days post operation
Number of Cardiogenic shock events	Cardiogenic shock (i.e. tissue hypoperfusion presented by hypotension due to decreased cardiac output, determined by rising lactate levels (5x normal levels in first 24 hours, 2.5x normal levels in first 30 days)	Day 1, 30 days post operation
Number of unplanned cardiovascular operation events	Unplanned cardiovascular operation due to right ventricular intramyocardial injection site bleeding in the first 5 days after Stage II operation decreased cardiac output, determined by rising lactate levels (5x normal levels in first 24 hours, 2.5x normal levels in first 30 days)	30 days post operation
Number of patients requiring new permanent pacemaker	Number of patients requiring new permanent pacemaker	upto 30 days post operation
Stroke or embolic event	Stroke or embolic event to the brain determined by CT scan	upto 30 days post operation
Number of Adverse Events	Number of adverse events occurring post op	upto 30 days post operation
Number of deaths	Number of deaths occurring post op	upto 30 days post operation
Number of VentriGel products manufactured and delivered to subjects		12 months
Number of patients receiving Cardiac MRIs		Baseline, 6 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in right ventricular ejection fraction	This will be measured by serial echocardiograms and MRI scans	Baseline, 6 months, 12 months post operation
Change in right ventricular end diastolic volume	This will be measured by serial echocardiograms and MRI scans	Baseline, 6 months, 12 months post operation
Change in right ventricular end systolic volume	This will be measured by serial echocardiograms and MRI scans	Baseline, 6 months, 12 months post operation
Change in tricuspid regurgitation	This will be measured by serial echocardiograms and MRI scans. tricuspid regurgitation measured by tricuspid valve vena contracta width	Baseline, 6 months,12 months post operation
Change in right ventricular function Fractional Area Change	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Change in right ventricular global longitudinal strain	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Change in right ventricular global circumferential strain	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Change in right ventricular Tricuspid Annular Plane Systolic Excursion (TAPSE)	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Change in right atrial volume indexed	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: University of California, San Diego; Ventrix, Inc.
• Investigators: Principal Investigator: William Mahle, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: May 28, 2024
• First Submitted That Met QC Criteria: June 14, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: HLHS; Stage II Glenn operation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Syndrome; Hypoplastic Left Heart Syndrome
• Other Study ID Numbers: STUDY00006965

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No