Optimum Dose of rhCC10 for Lung Protection in IRDS

描述(从申请人的描述中扫描)：拟议的研究 包括评估重组人CC10在体内的剂量反应 早产羔羊--一种依赖表面活性物质的新生儿/婴儿呼吸模型 窘迫综合征(IRDS)。临床应用早产羔羊模型。 治疗红斑狼疮的人工表面活性剂的发展。CC10是 通常由猪的气管和支气管上皮的Clara细胞分泌 成熟的肺。它在肺的细胞外液中含量丰富，并且 内源性表面活性物质的天然成分。类似于表面活性剂，CC10是 不存在于早产儿的肺中。初步结果表明， 事实上，CC10对正常的肺功能是必不可少的，而这是一种替代 应用重组人CC10的策略可能有效地减轻肺部炎症和 早产儿慢性肺部疾病(CLD)的发生率 呼吸窘迫。大剂量给予重组人CC10的安全性 已经在新生小猪的临床前研究中得到了证实。一个 优化剂量反应以最大限度保护肺和肺的对照研究 确定衡量重组人CC10疗效的临床参数 结合人工表面活性物质，在早产表面活性物质依赖模型中 现已提出。 建议的商业应用： CC10目前处于rhCC10临床开发的第一阶段，用于预防新生儿支气管-肺发育不良。本研究对设计有效的给药策略具有重要意义。 用于进一步的临床开发。根据最近的估计，大约有9万人 美国每年都有早产儿出生。在这些人中，大约有5万人将生下婴儿 呼吸窘迫综合征(IRDS)和20,000名患有IRDS的婴儿将发展为 BPD或某种形式的慢性肺部疾病。每年在医院治疗这些婴儿的费用 生命的前三个月每人约为20万美元，每年至少花费 40亿美元。这些婴儿中的许多人在整个童年时期都有呼吸问题。 而且这种持续护理的费用没有包括在40亿美元/年的估计数中。 重组人CC10有可能预防这种疾病，减少每年的 照顾这些孩子的经济负担。RhCC10也可能在治疗中发挥重要作用 许多儿科和成人呼吸道疾病也是如此。

DESCRIPTION (Scanned from the applicant's description): The proposed study involves an evaluation of the dose response to recombinant human CC10 in the preterm lamb, a surfactant-dependent model of neonatal/infant respiratory distress syndrome (IRDS). The preterm lamb model was used in the clinical development of artificial surfactants for the treatment of IRDS. CC10 is normally secreted by the Clara cells of the tracheal and bronchial epithelia of the mature lung. It is abundant in the extracellular fluids of the lungs and is a natural component of endogenous surfactant. Analogous to surfactant, CC10 is not present in the lungs of preterm babies. Preliminary results indicate that CC10 is, in fact, essential to normal lung function, and that a replacement strategy with rhCC10 may be effective in reducing pulmonary inflammation and incidence of chronic lung disease (CLD) in premature babies treated for respiratory distress. The safety of administration of high doses of rhCC10 has already been established in pre-clinical studies in newborn piglets. A controlled study to optimize the dose response for maximal lung protection and define the clinical parameters to measure efficacy of rhCC10, administered in conjunction with artificial surfactant, in a preterm surfactant dependent model of IRDS, is now proposed. PROPOSED COMMERCIAL APPLICATION: CC10 is currently in Phase I of clinical development of rhCC10 for the prevention of neonatal broncho-pulmonary dysplasia. This study is important in designing effective dosing strategies for further clinical development. According to recent estimates, approximately 90,000 premature babies are born in the U.S. each year. Of those, about 50,000 will have infant respiratory distress syndrome (IRDS) AND 20,000 of those babies with IRDs will develop BPD or some form of chronic lung disease. The annual cost of treating these babies in the first three months of life is about $200,000 each for an annual expense of a minimum of $4 billion. Many of these babies continue to have respiratory problems throughout childhood and the cost of this continued care have not been included in the $4 billion/year estimate. Recombinant human CC10 has the potential to prevent this disease and reduce the annual economic burden of caring for these children. RhCC10 may also be important in treating many pediatric and adult respiratory diseases as well.