Project Grant R44HL147361

PHASE IIB TRANSMURAL SYSTEMS TRANSCATHETER CAVOPULMONARY BYPASS ENDOGRAFT - PROJECT SUMMARY TRANSMURAL SYSTEMS LLC HAS DEVELOPED A PURPOSE-BUILT TRANSCATHETER CAVOPULMONARY BYPASS ENDOGRAFT (TCBE) THAT WILL ALLOW FOR INTERVENTIONAL CARDIOLOGISTS TO TREAT CHILDREN BORN WITH FUNCTIONAL SINGLE VENTRICLE (FSV), A FORM OF CYANOTIC CONGENITAL HEART DISEASE. CHILDREN BORN WITH FSV REPRESENT 7.7% OF ALL PATIENTS WITH CONGENITAL HEART DEFECTS (CHD). IN THE UNITED STATES, ABOUT 2000 CHILDREN ARE BORN WITH FSV EACH YEAR. FSV IS AN UMBRELLA TERM APPLIED TO SEVERAL COMPLEX CHDS, WHICH INCLUDES HYPOPLASTIC LEFT HEART SYNDROME (HLHS), PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM, TRICUSPID ATRESIA, AND UNBALANCED ATRIOVENTRICULAR CANAL, AMONG OTHERS. WITHOUT TREATMENT, THE ACTUARIAL SURVIVAL RATES OF PATIENTS WITH FSV ARE ONLY 53% AT ONE YEAR AND 42% AT TEN YEARS OF AGE. THE DEVELOPMENT OF PALLIATIVE SURGICAL PROCEDURES, HOWEVER, HAS MARKEDLY IMPROVED THE SURVIVAL OF PATIENTS WITH FSV, BUT THESE SURGERIES AND SUBSEQUENT LENGTHY STAYS IN THE CARDIOVASCULAR INTENSIVE CARE UNIT CONTRIBUTE SIGNIFICANTLY TO MORTALITY AND MORBIDITY OF FSV PATIENTS. A LESS INVASIVE CLINICAL ALTERNATIVE HAS NOT TO DATE BEEN AVAILABLE FOR THESE SURGICAL PROCEDURES. A TRANSCATHETER ALTERNATIVE WOULD OFFER THE POSSIBILITY OF REDUCED MORTALITY AND MORBIDITY, AS WELL AS REDUCED HOSPITAL STAYS AND RELATED COSTS. THUS, THERE IS AN URGENT CLINICAL NEED FOR AN EFFECTIVE PERCUTANEOUS APPROACH TO TREATING FSV. IN A PREVIOUS PHASE II CONTRACT, TRANSMURAL SYSTEMS ENGINEERED THE TCBE, INTENDED TO CREATE A BI-DIRECTIONAL GLENN SHUNT BETWEEN THE SUPERIOR VENA CAVA AND RIGHT PULMONARY ARTERY. THE TCBE DESIGN HAS BEEN OPTIMIZED AND EXTENSIVELY TESTED IN VASCULAR BENCH MODELS AND IN ACUTE AND CHRONIC GOOD LABORATORY PRACTICES (GLP) SWINE EXPERIMENTS. THE TCBE HAS PERFORMED WITH EXCELLENT EFFICIENCY AND SAFETY IN THESE EXPERIMENTS. THE GOAL FOR THIS PHASE IIB PROJECT IS TO UTILIZE TRANSMURAL'S TCBE IN A CLINICAL TRIAL TO TEST THE SAFETY AND THERAPEUTIC VALUE IN TREATING FSV PATIENTS. AN EARLY FEASIBILITY STUDY (EFS) WILL BE THE FOCUS OF THIS PHASE IIB AWARD. TRANSMURAL SYSTEMS WILL BE SIGNIFICANTLY GUIDED BY THE EXPERTISE OF DR. ROBERT J. LEDERMAN OF THE NHLBI, DR. KANISHKA RATNAYAKA OF THE NHLBI AND RADY CHILDREN'S HOSPITAL, DR. JOHN MOORE, DR. JOHN NIGRO, AND DR. HOWAIDA EL-SAID, ALL OF RADY CHILDREN'S HOSPITAL, WHO WILL ASSIST IN RUNNING AND CONDUCTING CLINICAL STUDIES. THE GOAL OF EFS COMPLETION WILL BE ACHIEVED THROUGH THE EXECUTION OF THE FOLLOWING SPECIFIC AIMS: 1) MANUFACTURE AND STERILIZE A BATCH OF TCBE DEVICES UTILIZING GOOD MANUFACTURING PRACTICES (GMP) FOR PRECLINICAL TESTING AND TO SUPPORT EFS; 2) EXECUTE PRECLINICAL TESTING TO DEMONSTRATE THE TCBE DESIGN SPECIFICATIONS MEET THE DESIGN REQUIREMENTS, GENERATE A REPORT TO SUBMIT TO FOOD AND DRUG ADMINISTRATION (FDA) AS PART OF AN INVESTIGATIONAL DEVICE EXEMPTION (IDE) PACKAGE, AND RECEIVE APPROVAL TO START THE EFS; AND 3) COMPLETE ENROLLMENT OF EFS (UP TO N=10 SUBJECTS). THESE PROPOSED SPECIFIC AIMS ARE VITAL STEPS IN COMMERCIALIZING THE TCBE (THROUGH A FUTURE HUMANITARIAN DEVICE EXEMPTION TRIAL) THAT WILL BE THE ONLY DEVICE ON THE MARKET PURPOSEFULLY CREATED FOR FSV.