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)

Overview

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

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.

Interventions

• 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.

Primary outcome measures

• Number of ventricular tachycardia events [Time frame: upto 30 days post operation]
• Number of Cardiogenic shock events [Time frame: Day 1, 30 days post operation]
• Number of unplanned cardiovascular operation events [Time frame: 30 days post operation]
• Number of patients requiring new permanent pacemaker [Time frame: upto 30 days post operation]
• Stroke or embolic event [Time frame: upto 30 days post operation]
• Number of Adverse Events [Time frame: upto 30 days post operation]
• Number of deaths [Time frame: upto 30 days post operation]
• Number of VentriGel products manufactured and delivered to subjects [Time frame: 12 months]
• Number of patients receiving Cardiac MRIs [Time frame: Baseline, 6 months, 12 months]

Secondary outcome measures (9)

• Change in right ventricular ejection fraction [Time frame: Baseline, 6 months, 12 months post operation]
• Change in right ventricular end diastolic volume [Time frame: Baseline, 6 months, 12 months post operation]
• Change in right ventricular end systolic volume [Time frame: Baseline, 6 months, 12 months post operation]
• Change in tricuspid regurgitation [Time frame: Baseline, 6 months,12 months post operation]
• Change in right ventricular function Fractional Area Change [Time frame: Baseline, 6 months,12 months post operation]
• Change in right ventricular global longitudinal strain [Time frame: Baseline, 6 months,12 months post operation]
• Change in right ventricular global circumferential strain [Time frame: Baseline, 6 months,12 months post operation]
• Change in right ventricular Tricuspid Annular Plane Systolic Excursion (TAPSE) [Time frame: Baseline, 6 months,12 months post operation]
• Change in right atrial volume indexed [Time frame: Baseline, 6 months,12 months post operation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Children's Healthcare of Altanta — Atlanta

Identifiers

NCT: NCT06461676 · STUDY00006965

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗