Clinical study of aerosolized KL4 surfactant for neonatal RDS and BPD prevention

DESCRIPTIONprovided by applicantDiscovery LaboratoriesIncDiscoveryis developing a novel drug device combination therapyAEROSURF rthat employs an optimized proprietary capillary aerosol generatorCAGto deliver aerosolized surfactantlucinactantto preterm infants with or at risk for respiratory distress syndromeRDSand who may subsequently develop a chronic lung disease known as bronchopulmonary dysplasiaBPDLucinactantSURFAXIN rIntratracheal Suspensionis Discovery LabsproprietarysyntheticKLpeptide containing surfactant that was approved by the US FDA infor endotracheal administration for the prevention of RDS in preterm infantsThis grant proposal is being submitted as follow on to an SBIR Fast track grant awarded to DiscoveryPhase I supported the development of a clinic ready CAG device for aerosolization of lucinactantPhase II funded a completed Phasea pilot clinical study in preterm infants on nasal continuous positive airway pressurenCPAPwith RDS and at risk for developing BPDdisease areas targeted by the NHLBI RFAsBPD occurs in excess ofpercent in preterm infants belowweeks gestation ageand is a very costly disease associated with significant mortality and long term morbidityThe primary therapy for RDS is surfactant replacement therapySRTand mechanical ventilationMVSRT currently requires intratracheal instillation via an endotracheal tubeETTfor effective delivery to the lungAlthough ETT intubationMV and SRT are lifesavingthey are associated with iatrogenic complications include airway traumaincreased the risk of infectionand voluand baro traumaall of which have been implicated in the development of BPDIn order to avoid these sequelaenCPAP is increasingly being used to support preterm infants with respiratory insufficiencyHoweveruse of nCPAP typically precludes preterm infants from receiving SRTand half of these infants subsequently require intubationlate surfactant therapyand mechanical ventilationincreasing the risk for BPDLimited success has been achieved to date in non ETT delivery of surfactants with existing aerosol generating devicesthus our development of AEROSURFWe plan to evaluate aerosolized lucinactantAEROSURFin a largernfollow on study in preterm infants on nCPAP to establish safety and to estimate effectiveness of the drug device combination product in preventing nCPAP failureand reducing the incidence of severe RDS and BPD as key outcomesSpecificallywe will conduct a multicenterrandomizedopen label Phaseb clinical study of two doses of AEROSURFthat are based on outcomes from the phasea clinical studyOutcomes will focus on safetyserious adverse events and adverse device eventsand efficacythe later will be assessed primarily by the incidence of treatment failureSecondary efficacy measures will include improvements in oxygenation and reduction in need for ventilator supportto be assessed throughhrsanddays after birthas well as the incidence of BPD atweeks PMAfollow up of infants throughyear corrected age is also planned