An Improved Method of Delivering a Sclerosing Agent for the Treatment of a Malignant Pleural Effusion.

一种输送硬化剂治疗恶性胸腔积液的改进方法。

• 批准号: 9888334
• 负责人: RICHARD Brian HUNEKE
• 金额: $ 95.97万
• 依托单位: TDL INNOVATIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888334
• 关键词: Address; Adhesions; Adhesiveness; Advanced Malignant Neoplasm; Affect; Animal Model; Animal Testing; Cancer Patient; Capital; Characteristics; Chemicals; Chemistry; Chest; Chest Tubes; Chest wall structure; Client satisfaction; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Complication; Consensus; Control Groups; Data; Development; Devices; Drainage procedure; Drug Combinations; Drug Delivery Systems; Effectiveness; Engineering; Ensure; Evaluation; FDA approved; Failure; Feasibility Studies; Formulation; Funding; Gamma Rays; Gel; Generations; Goals; Gold; Grant; Guidelines; Histopathology; Human; Hydrogels; In Vitro; Instruction; Intervention; Lead; Liquid substance; Lung; Malignant Neoplasms; Malignant Pleural Effusion; Measures; Mechanics; Medical; Medical Device; Methods; Modeling; Oryctolagus cuniculus; Outcome; Palliative Care; Pamphlets; Parietal pleura; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pleural cavity; Pleurodesis; Preparation; Procedures; Process; Property; Protocols documentation; Quality of life; Regulatory Pathway; Reproducibility; Research Personnel; Safety; Saline; Sclerosing Agents; Selection Criteria; Shortness of Breath; Site; Small Business Innovation Research Grant; Source; Standardization; Sterility; Sterilization; Surgeon; System; Talc; Techniques; Temperature; Testing; Tissues; Toxicology; Training; Transition Temperature; Treatment Failure; United States Food and Drug Administration; Visceral pleura; Viscosity; biomaterial compatibility; body system; clinical application; clinical practice; clinically relevant; cost; design; disabling symptom; efficacy testing; experience; first-in-human; implantation; improved; innovation; interest; lead candidate; lead optimization; minimally invasive; multidisciplinary; novel; novel strategies; palliative; phase 1 study; pre-clinical; pressure; prevent; process optimization; programs; propellant; prototype; reduce symptoms; research and development; safety assessment; stability testing; standard of care; usability

Project Summary / Abstract. We are developing an improved clinical method to treat patients with malignant pleural effusions (MPE), a serious condition that occurs in 150,00-175,000 patients in the US each year, affecting between 7 to 15% of all cancer patients. MPE results in an excessive accumulation of liquid in the pleural cavity, frequently leaving the patient to suffer from shortness of breath and overall poor quality of life in their remaining months. Management of MPE is palliative and the main problem with the current techniques such as pleurodesis is its frequent clinical failure rate due to the inefficient and non-uniform distribution of the sclerosing agent. Currently, there is no standardization and consensus within the medical community on the optimal delivery technique for a sclerosing agent because of the tradeoffs and variability in patient satisfaction, efficacy, costs, and complexities. This has led to little progress and many of the current clinical gold standard techniques have not evolved in over 80 years. Our focus is on the development of an improved clinical approach to administering a sclerosing agent, which will overcome the problems with those currently practiced methods. In Phase I feasibility studies, we developed and evaluated several foam formulations and have selected a lead candidate. We fully characterized the lead, demonstrating its desired adhesiveness, gelation and reverse thermo-sensitive properties as well as its efficacy in an animal model. These results enable us to proceed with optimization of the lead in parallel with finalizing the design of our proprietary delivery system in this proposed Phase II project. The objectives of the study will be to generate a fully functional prototype with complete manufacturing specifications and user guides, and to also evaluate the safety and efficacy of the lead formulation during biocompatibility studies conducted under GLP conditions, in order to prepare a data package for an IND application to the Food and Drug Administration. Once successfully completed, these Phase II results will prepare us to initiate first-in-human clinical trials where we will test the functional prototype of our combination drug device in collaboration with several prestigious clinical partners who are an important part of this Phase II team. Our multidisciplinary team lead by an experienced cardiothoracic surgeon, has the demonstrated requisite expertise ranging from innovating in chemical and mechanical engineering, navigating the FDA regulatory pathway for combination products, successfully commercializing pharmaceutical and medical device products, to successfully exiting companies. The funding sought through the SBIR Phase II program will be critical to enable us to achieve important R&D milestones that we will further leverage for attracting outside sources of capital from investors, many who are already expressing interest. Our novel approach is expected to significantly impact the current clinical standard of care and result in markedly improved clinical patient outcomes with a simple, minimally invasive procedure.

项目概要/摘要。 我们正在开发一种改进的临床方法来治疗恶性胸腔积液（MPE）患者， 美国每年有150，00 - 175，000名患者发生严重疾病，影响7%至15%的 所有癌症患者。MPE导致胸膜腔中液体过度积聚， 患者在其剩余的几个月中遭受呼吸短促和总体生活质量差。 MPE的治疗是姑息性的，目前的技术如胸膜固定术的主要问题是其 由于硬化剂的低效和不均匀分布而导致的频繁的临床失败率。 目前，医学界对最佳分娩没有标准化和共识 由于患者满意度、功效、成本 和复杂性。这导致进展甚微，目前许多临床金标准技术 已经80多年没有进化了我们的重点是开发一种改进的临床方法， 施用硬化剂，这将克服那些目前实施的方法的问题。 在第一阶段的可行性研究中，我们开发和评估了几种泡沫配方，并选择了一种 主要候选人。我们充分表征了铅，证明了其所需的稳定性，凝胶化和 逆转热敏特性以及其在动物模型中的功效。这些结果使我们能够 在完成我们的专有输送系统设计的同时，继续优化电极导线， 这是第二阶段计划。这项研究的目标将是生成一个功能齐全的原型， 完整的制造规范和用户指南，并评估 在GLP条件下进行的生物相容性研究期间的主要制剂，以准备数据 向食品和药物管理局提交IND申请的包装。一旦成功完成，这些 第二阶段的结果将使我们准备开始首次在人体临床试验，我们将测试功能 我们的组合药物设备的原型与几个著名的临床合作伙伴合作，他们是一个 第二阶段团队的重要组成部分。我们的多学科团队由经验丰富的心胸外科医生领导， 外科医生，具有从化学和机械创新 工程，为组合产品导航FDA监管途径，成功商业化 制药和医疗器械产品，以成功退出公司。通过以下方式筹集资金 SBIR第二阶段计划将是至关重要的，它将使我们能够实现重要的研发里程碑，我们将 进一步吸引投资者的外部资本来源，许多人已经表示， 兴趣我们的新方法预计将显著影响目前的临床护理标准和结果 通过简单的微创手术，显着改善了临床患者的预后。