Development & Utilization of a Novel Aerosol-Generating Technology to Deliver Luc

发展

• 批准号: 8058373
• 负责人: Robert Segal
• 金额: $ 58.18万
• 依托单位: DISCOVERY LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8058373
• 关键词: Acute; Aerosols; Animal Model; Animals; Applications Grants; Blood capillaries; Breathing; Bronchopulmonary Dysplasia; Chemical Surfactants; Chemicals; Chronic lung disease; Clinic; Clinical Research; Combined Modality Therapy; Complication; Development; Devices; Dose; Drug Impurity; Engineering; Ensure; Evaluation; Generations; Grant; Healthcare; Infant; Intratracheal Intubation; Intubation; Investigational Drugs; Laboratories; Lead; Lung; Lung diseases; Maximum Tolerated Dose; Mechanical ventilation; Morbidity - disease rate; Particle Size; Patients; Peptides; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Population; Premature Infant; Prevention; Prevention strategy; Randomized; Replacement Therapy; Risk; Safety; Small Business Innovation Research Grant; System; Target Populations; Technology; Testing; Therapeutic; Time; Tube; United States Food and Drug Administration; Ventilator; aerosolized; arm; capillary; cost; design; drug testing; endotracheal; meetings; mortality; nCPAP Ventilation; neonate; novel; open label; phase 3 study; prototype; respiratory distress syndrome; standard of care; success; surfactant

DESCRIPTION (provided by applicant): Respiratory distress syndrome (RDS) is an acute, severe pulmonary disorder that is the leading cause of morbidity and mortality in preterm infants. It is a major healthcare concern - costs associated with treatment of RDS and its complications exceed $2.4 billion annually in the US. Currently, animal-derived surfactants instilled intratracheally via an endotracheal tube (ETT) are standard of care for treating RDS, in conjunction with mechanical ventilation (MV). ETT intubation and MV are often associated with iatrogenic complications and may lead to bronchopulmonary dysplasia (BPD)/ chronic lung disease (CLD) in these infants. Thus, non-invasive ventilator strategies such as nasal continuous positive airway pressure (nCPAP) are being increasingly employed, but use of nCPAP precludes the use and benefits of early surfactant replacement therapy. Limited success has been achieved in delivering surfactants with currently available aerosol-generating devices. To overcome the critical barrier of effectively aerosolizing surfactant, Discovery Laboratories Inc. (Discovery Labs) is developing an aerosolization technology platform that is specifically designed to noninvasively deliver its proprietary KL4 peptide-containing synthetic surfactant (lucinactant). The objective of developing this "first-in-class" drug-device combination therapy is to obviate the need for ETT intubation to deliver surfactants to preterm infants with or at risk for RDS, and second, avoid the use of animal- derived products in this fragile population. Prototype and first generation aerosol devices and delivery systems have been developed, demonstrating technical feasibility of delivering aerosolized lucinactant; efficacy has also been demonstrated in a preterm animal model (lamb) of RDS. Discovery Labs is currently developing a second generation device, which it plans to take into the clinic. The objective of the Phase I proposal is to fully test this device and conduct characterization of the aerosolized drug product to ensure that it is optimized for delivery to preterm infants. Following completion of Phase I, Discovery Labs intends moving to the Phase II objective of conducting a pilot phase 2a, open-label, multicenter, dose escalation trial in preterm infants with or at risk for RDS. Although beyond the scope of this proposal, an expanded phase 2b study will be conducted, to be followed by a pivotal, Phase 3, which should support submission of an NDA for the dug-device combination product as a therapeutic strategy for prevention and treatment of RDS. PUBLIC HEALTH RELEVANCE: Respiratory distress syndrome (RDS), a severe lung disorder that is the most commonly seen complication in infants born prematurely is a significant health-care concern, costing in excess of $2.4 billion annually. RDS is currently treated with animal-derived surfactants that can only be administered via invasive endotracheal intubation of the infant airway, and mechanical ventilation, both of which have risks. Discovery Laboratories Inc. is developing a "first-in-class" drug-device combination therapy using a novel aerosol technology to noninvasively deliver its synthetic surfactant, and hence obviate the need for intubation to deliver surfactants to preterm infants with RDS, and at the same time, avoid the use of animal-derived products in this fragile population.

描述（由申请人提供）：呼吸窘迫综合征（RDS）是一种急性，严重的肺部疾病，是早产儿发病和死亡率的主要原因。这是一个主要的医疗保健问题 - 与RDS治疗相关的成本及其并发症在美国每年超过24亿美元。当前，通过气管内管（ETT）在气管内灌输动物的表面活性剂是治疗RDS的标准，并与机械通气（MV）结合使用。 ETT插管和MV通常与医源性并发症有关，可能导致支气管肺发育不良（BPD）/慢性肺病（CLD）。因此，越来越多地利用了鼻腔连续气道压力（NCPAP）等非侵入性呼吸机策略，但是使用NCPAP可以排除早期表面活性剂替代疗法的使用和益处。 在交付目前可用的气溶胶生成设备的表面活性剂方面取得了有限的成功。为了克服有效的气化表面活性剂的关键障碍，Discovery Laboratories Inc.（Discovery Labs）正在开发一个雾化技术平台，该平台是专门设计用于非侵入性提供其专有KL4肽合成表面活性剂（LucInactant）的。开发这种“一流的”药物磁盘组合疗法的目的是消除ETT插管的需求，以将表面活性剂传递给患有RDS或有风险的早产儿，其次，避免在此脆弱人群中使用动物衍生的产物。已经开发了原型和第一代气溶胶设备和输送系统，证明了递送燃气蛋白活性剂的技术可行性；在RDS的早产动物模型（LAMB）中也证明了功效。 Discovery Labs目前正在开发第二代设备，该设备计划进入诊所。 I期建议的目的是对该设备进行充分测试并进行雾化药物的表征，以确保将其优化以送给早产儿。 I阶段完成后，Discovery Labs打算转到II阶段的目标，即进行2A阶段，开放标签，多中心，剂量升级试验的早产儿或有RDS风险。尽管除了该提案的范围之外，还将进行一项扩展的2B期研究，然后进行关键，第3阶段，该研究应支持提交NDA作为DUG-Device组合产品作为预防和治疗RDS的治疗策略。 公共卫生相关性：呼吸窘迫综合征（RDS），一种严重的肺部疾病，过早出生的婴儿最常见的并发症是一个重大的医疗保健问题，每年的成本超过24亿美元。目前，RDS经过动物衍生的表面活性剂处理，只能通过婴儿气道的侵入性气管插管和机械通气进行治疗，它们都有风险。 Discovery Laboratories Inc.正在使用一种新型的气溶胶技术开发一种“一流的”药物磁盘组合疗法，以非侵入性地提供其合成表面活性剂，因此消除了插管的必要性，以将表面活性剂交付给具有RDS的早产儿，同时避免在这种脆弱的脆弱的人群中使用动物衍生的产品。