Feasibility Study to Evaluate the Safety of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve

A First-in-Human Feasibility Study to Evaluate the Safety (and Short Term Effectiveness) of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve [GECT]

Aim of this study is to investigate the clinical safety of a novel pediatric heart valve.

Defective or diseased pulmonary heart valves do not recover. If left untreated, pediatric and adult patients alike, face serious risks of progressive heart failure and death. Due to the insufficient care of children with heart valve defects, the valve replacement with regenerative, remodeling, and growth potential remains an unmet medical need. Therefore, the first pediatric heart valve (GrOwnValve) was developed to overcome the current limitations, which should offer regenerative potential that adapts to the somatic growth of the child. The study aims to investigate the safety and provide the first initial efficacy estimates of the transcatheter implantable GrOwnValve. This first prospective, non-randomized, single center trial in 7 study subjects (≥ 18 years of age) should be conducted to assess the devices safety for clinical application.

The novel interdisciplinary solution approach is based on the combination of individualized 3D modeling, viable autologous tissue (contrary to all other prosthetic heart valves on the market), and preservation of the regenerative capacity of the valve replacement by maintaining the vitality of heart valve cells and tissue through the application of a novel crosslinker in the tissue preparation process. The GrOwnValve prothesis has the potential to be the first durable and regenerative heart valve for adults. Fabrication is performed on-demand in the operating room. The trial should be the first clinical investigation assessing this novel heart valve replacement approach. We are aiming for the GrOwnValve to be the standard of care, replacing current solutions.

Inclusion Criteria:

1. Age ≥ 18 years

2. Sufficient appropriate tissue (preferably: Pericardium for pericardiectomy via thoracoscopy or thoracotomy, or sternotomy; other options are fascia lata, rectus fascia, peritoneum or diaphragm)

3. Any of the following by transthoracic echocardiography and/or Cardiac Magnet Resonance Imaging:

   • For patients in New York Heart Association (NYHA) Classification II, III, or IV: Moderate (3+) or severe (4+) pulmonary regurgitation AND/OR mean systolic gradient across PV or RVOT ≥ 35 mmHg
   • For patients in NYHA Classification I: Severe (4+) pulmonary regurgitation with RV dilatation or dysfunction and/or mean PV or RVOT systolic gradient ≥ 40 mmHg
   • Right ventricular ejection fraction (RV-EF): <40%.
   • Right ventricular end-diastolic volume (RVEDV): >150 ml/m2 (body surface area)

4. Written informed consent provided by study subjects obtained before any research-related test is performed

Exclusion Criteria:

• Active endocarditis or myocarditis or within 3 months before the screening date
• Patients unwilling or unable to provide written informed consent or comply with follow-up requirements
• Obstruction of the central veins (including the superior and inferior vena cava, and bilateral iliac veins) such that the Ensemble-delivery system/ Performer™ - Guiding Sheath/ Extra Large Check-Flo® or GORE® DrySeal Flex + Ballon-in-Ballon-catheter cannot be advanced to the heart via a transvenous approach from either femoral vein or internal jugular
• Requires emergency surgery
• Recipient of transplanted organs or currently an organ transplant candidate
• Pulmonary hypertension
• Connective tissue disorders
• Coronary artery disease
• Immunosuppressive disease
• Estimated survival of less than 6 months
• Fertile females unable to take adequate contraceptive precautions (PEARL- Index < 1%)
• Females who are pregnant, or are currently breastfeeding an infant
• Acute myocardial infarction within 30 days of the screening date
• Stroke confirmed by CT, cerebrovascular accident (CVA), or transient ischemic attack (TIA) within 6 months before the screening date
• Hemodynamic or respiratory instability requiring inotropic or/and mechanical circulatory support, or mechanical ventilation within 30 days before the screening date
• Severe left ventricular systolic dysfunction with ejection fraction ≤ 20% or evidence of an intra-cardiac mass, thrombus, or vegetation assessed by echocardiography before the screening date
• Renal insufficiency with creatinine level 2.5 mg/dl within 60 days before the screening date
• Leukopenia with WBC <3.5 x 109/L anemia with Hgb <10 g/dl, or thrombocytopenia with platelet count <50x103/l accompanied by a history of bleeding diathesis or coagulopathy within 60 days before the screening date
• Adult subject is an illicit drug user, alcohol abuser, or unable to give informed consent
• Subject is institutionalized by court order or by order of authority (e.g. prisoner, untreated psychiatry; limited compliance)
• Major or progressive non-cardiac disease (liver failure, renal failure, cancer)that has a life expectancy of less than six months Inability to comply with all of the study procedures and follow-up visits
• Subjects who are dependent on the sponsor or investigators