Optimum Dose of rhCC10 for Lung Protection in IRDS

rhCC10 保护 IRDS 肺部的最佳剂量

• 批准号: 6344251
• 负责人: APRILE L PILON
• 金额: $ 10万
• 依托单位: CLARAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-02 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6344251
• 关键词: biotherapeutic agent; cytoprotection; dosage; drug administration routes; drug screening /evaluation; glycoproteins; histochemistry /cytochemistry; newborn animals; phospholipase inhibitor; pulmonary surfactants; recombinant proteins; respiratory disorder chemotherapy; respiratory distress syndrome of newborn; respiratory epithelium; respiratory pharmacology; sheep

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.

描述（从申请人的描述中扫描）：拟议的研究 涉及对重组人 CC10 的剂量反应的评估 早产羔羊，新生儿/婴儿呼吸表面活性剂依赖性模型 窘迫综合症（IRDS）。早产羔羊模型应用于临床 开发用于治疗IRDS的人工表面活性剂。 CC10 是 通常由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， 内源性表面活性剂的天然成分。与表面活性剂类似，CC10 是 早产儿的肺部不存在。初步结果表明 事实上，CC10 对于正常的肺功能至关重要，并且是替代品 rhCC10 策略可能有效减少肺部炎症 接受治疗的早产儿慢性肺病（CLD）的发病率 呼吸困难。高剂量 rhCC10 给药的安全性 已在新生仔猪的临床前研究中建立。一个 对照研究优化剂量反应以实现最大肺保护和 定义临床参数来测量 rhCC10 的功效， 与人工表面活性剂结合，在早产表面活性剂依赖模型中 IRDS，现在被提议。 拟议的商业应用： CC10 目前正处于 rhCC10 临床开发的 I 期，用于预防新生儿支气管肺发育不良。 这项研究对于设计有效的剂量策略很重要 以进行进一步的临床开发。 根据最近的估计，大约有 90,000 美国每年都会有早产儿出生。 其中，约 50,000 人将生下婴儿 呼吸窘迫综合征 (IRDS)，其中 20,000 名患有 IRD 的婴儿将患上呼吸窘迫综合征 (IRDS) BPD 或某种形式的慢性肺部疾病。 每年治疗这些婴儿的费用 生命的前三个月每年大约花费 200,000 美元，至少 40 亿美元。 其中许多婴儿在整个童年时期仍然存在呼吸系统问题 而且这种持续护理的费用并未包含在每年 40 亿美元的估计中。 重组人 CC10 有潜力预防这种疾病并减少每年的发病率 照顾这些孩子的经济负担。 RhCC10 在治疗中也可能很重要 许多儿童和成人呼吸道疾病。

项目成果

Dose response to rhCC10-augmented surfactant therapy in a lamb model of infant respiratory distress syndrome: physiological, inflammatory, and kinetic profiles.

婴儿呼吸窘迫综合征羔羊模型中 rhCC10 增强表面活性剂治疗的剂量反应：生理、炎症和动力学特征。

• 发表时间: 2005-12
• 作者: Shashikant, Beth N;Miller, Thomas L;Welch, Richard W;Pilon, Aprile L;Shaffer, Thomas H;Wolfson, Marla R
• 通讯作者: Wolfson, Marla R