Clinical Development a Therapeutic Agent for COPD

慢性阻塞性肺病治疗剂的临床开发

• 批准号: 7053538
• 负责人: Indu Parikh
• 金额: $ 100万
• 依托单位: BIOMARCK PHARMACEUTICALS, LTD
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053538
• 关键词: bronchial mucus; chronic obstructive pulmonary disease; clinical research; clinical trial phase I; clinical trial phase II; dosage; drug adverse effect; drug screening /evaluation; electrocardiography; human subject; human therapy evaluation; inhalation drug administration; inhibitor /antagonist; mucus; patient oriented research; peptide analog; pharmacokinetics; respiratory disorder chemotherapy; respiratory epithelium; respiratory pharmacology; secretion; spirometry; sputum

Hypersecretion of mucus into the respiratory airways is a major contributing factor in several lung diseases, including chronic pulmonary disease (COPD), asthma, cystic fibrosis, and bronchiectasis. Despite the obvious medical importance, there presently are no effective therapies to control excess mucus secretion in these diseases, and very few potential therapeutic targets. We discovered that a specific protein called MARCKS is a key molecule in the mucus secretary pathway. Based on this finding BioMarck developed a novel peptide, which inhibited mucus hypersecretion in human airway epithelial cells in culture and in a rodent model of asthma. With funding from SBIR Phase I and Phase II grants, BioMarck continued work on this project, has accomplished GMP manufacturing of a peptide (BIO-11006) that inhibits MARCKS, and successfully finished the nondinical safety studies of BIO-11006 in order to support an Investigational New Drug (IND) application to the FDA. This SBIR Phase II Competing Continuation grant application, if funded, will allow BioMarck to file an IND with FDA and conduct a dose-escalating, placebo-controlled, double-blind Phase 1 clinical trial in 56 healthy volunteers designed to evaluate the safety and tolerability of BIO-11006. This will be followed by testing BIO-11006 efficacy and pharmacodynamics in 184 COPD patients in a multi-center double-blind, placebo-controlled Phase 2a clinical trial. This project, if successful will lead to commercialization of BIO-11006 by providing data required for further expanded clinical trials in collaboration with a large pharmaceutical company. Worldwide, the sodal and economic burden of COPD is enormous. COPD, being the fourth leading cause of death, accounts for over 3 million deaths each year worldwide. The respiratory market is desperate for effective drugs for the treatment of asthma and COPD.

粘液分泌过多进入呼吸道是导致多种肺部疾病的主要因素，包括慢性肺病（COPD）、哮喘、囊性纤维化和支气管扩张。尽管具有明显的医学重要性，但目前还没有有效的疗法来控制这些疾病中过多的粘液分泌，并且潜在的治疗靶点也很少。我们发现一种称为 MARCKS 的特定蛋白质是粘液分泌途径中的关键分子。基于这一发现，BioMack 开发了一种新型肽，可抑制培养物和啮齿动物中人类气道上皮细胞的粘液过度分泌 哮喘模型。在 SBIR 一期和二期拨款的资助下，BioMack 继续开展该项目，完成了抑制 MARCKS 的肽 (BIO-11006) 的 GMP 生产，并成功完成了 BIO-11006 的非药物安全性研究，以支持向 FDA 申请研究性新药 (IND)。该 SBIR II 期竞争性延续拨款申请如果获得资助，将允许 BioMack 向 FDA 提交 IND 申请，并在 56 名健康受试者中进行剂量递增、安慰剂对照、双盲 1 期临床试验 志愿者旨在评估 BIO-11006 的安全性和耐受性。随后将在一项多中心双盲、安慰剂对照 2a 期临床试验中测试 BIO-11006 在 184 名 COPD 患者中的疗效和药效学。该项目如果成功，将通过与一家大型制药公司合作提供进一步扩大临床试验所需的数据，从而实现 BIO-11006 的商业化。在世界范围内，COPD 造成的社会和经济负担是巨大的。 COPD 是第四大死因，全世界每年有超过 300 万人死亡。呼吸系统市场迫切需要治疗哮喘和慢性阻塞性肺病的有效药物。