Manufacturing pathogen inactivated platelet lysate to treat corneal inflammation

制造病原体灭活血小板裂解物来治疗角膜炎症

• 批准号: 9048135
• 负责人: Edmund K Waller
• 金额: $ 14.93万
• 依托单位: CAMBIUM MEDICAL TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2016-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9048135
• 关键词: Address; Adoption; Adverse effects; Adverse event; Age; Allogenic; Alternative Therapies; Am 80; American; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Autoimmune Diseases; Autologous; Blood; Blood Platelets; Blood donor; Burn injury; Chronic; Clinical Research; Clinical Trials Design; Clinical effectiveness; Collection; Communicable Diseases; Complication; Cornea; Cyclosporine; Data; Disease Marker; Dose; Drug Formulations; Dry Eye Syndromes; EGF gene; Esthesia; Eye; Eyedrops; FDA approved; Faculty; Future; Generations; Growth Factor; Healed; Health; Hematopoietic Neoplasms; Hematopoietic Stem Cell Transplantation; In Vitro; Individual; Inflammation; Inflammation Mediators; Inflammatory; Keratoconjunctivitis Sicca; Legal patent; Marketing; Medical Technology; Methods; Modality; Morbidity - disease rate; Ophthalmology; Oryctolagus cuniculus; Patients; Pharmaceutical Preparations; Pharmacy facility; Phase; Plasma; Preparation; Procedures; Process; Production; Property; Qualifying; Quality Control; Research Contracts; Research Personnel; Rights; Safety; Sales; Serum; Sjogren' s Syndrome; Small Business Technology Transfer Research; Standardization; Sterility; Surface; Technology; Testing; Therapeutic; Therapeutic Uses; Time; Toxicology; Transplant Recipients; Treatment Efficacy; Universities; Work; alternative treatment; base; chronic graft versus host disease; commercialization; cytokine; design; dosage; experience; eye dryness; graft vs host disease; healing; hematopoietic cell transplantation; improved; large scale production; manufacturing process; medical schools; meetings; member; pathogen; preclinical study; public health relevance; research clinical testing; scale up; screening

 DESCRIPTION (provided by applicant): Ocular graft-versus-host disease (O-GVHD) is a particularly severe and debilitating complication of allogeneic hematopoietic stem cell transplantation (HSCT). O-GVHD develops in 60-90% of patients with chronic GVHD. Currently, Restasis (cyclosporine A, 0.05%) is the only FDA approved prescription topical medication to treat O-GVHD. In 2012, Restasis had sales of just under $1 billion for the treatment dry eye; however, the therapeutic efficacy of Restasis is only ~15%, and its use is associated with a 17% rate of adverse events. This lack of robust clinical effectiveness demonstrates that alternative therapies are needed. Many HSCT patients who fail Restasis therapy have found relief from using autologous serum formulated into topical eye drops (autologous serum tears, AST). Unfortunately, the lack of standardization of AST preparations (which are often prepared in doctor's offices or pharmacies), and challenges with its storage and administration, have limited widespread adoption of this product. In order to address the drawbacks of AST, we have developed a proprietary method to manufacture a promising alternative: a standardized platelet lysate preparation using pooled platelet collections (phPL) from qualified blood donors (Elate-OcularTM; Ocular-phPL). We believe Elate- OcularTM will be superior to Restasis or AST for treatment of patients with O-GVHD and other forms of dry eye since Elate-OcularTM is enriched (compared to serum) for a number of growth factors that promote corneal healing, has robust anti-inflammatory actions that can reduce ocular inflammation in patients with GVHD, and possesses bacteriostatic properties. This STTR Phase I application is submitted by Cambium Medical Technologies LLC, a start-up company founded by 4 faculty members from Emory University School of Medicine who developed Ocular-phPL. Emory will be the sub-contracting research organization for this application. Emory University has filed a patent application to protect our proprietary manufacturing process for phPL, and Cambium has exclusive rights to this patent and technology. The investigators have previously received two INDs from FDA CBER for other applications of phPL (IND14825-NCT01659762 and IND16191- NCT02359929), and we are now seeking to submit a treatment IND for Elate-OcularTM and conduct a Phase I/II clinical study in HSCT patients with O-GVHD. In order to support these clinical studies, we propose in this application to first further improve and validate the safety and efficacy profiles f Elate-OcularTM by: (i) demonstrating feasibility of applying a pathogen inactivation (PI) process during production of Elate- OcularTM; (ii) performing in vitro work on Elate-OcularTM (+/- PI treatment) to compare product compositions and mechanisms of action; and (iii) performing animal toxicology/efficacy studies with Elate-OcularTM (+/- PI treatment) in animals with a pre-existing inflammatory condition or deficient tear production. Successful completion of these aims will allow us to complete our FDA IND application and initiate the Phase I/II study (for which we will seek Phase II STTR support) in order to demonstrate that Elate- OcularTM is safe and well-tolerated in patients suffering O-GVHD morbidity, a required step toward future commercialization.

 描述（由应用提供）：眼移疗法宿主病（O-GVHD）是同种异体造血干细胞移植（HSCT）的特别严重且令人衰弱的并发症。 O-GVHD在60-90％的慢性GVHD患者中发展。目前，Restasis（环孢菌素A，0.05％）是FDA认可的处方局部用药治疗O-GVHD的唯一一种。 2012年，Restasis的销售额不到10亿美元。但是，Restasis的治疗效果仅为约15％，其使用与17％的不良事件率有关。缺乏强大的临床有效性表明需要替代疗法。许多失败Restasis疗法的HSCT患者已经缓解了使用将自体血清插入局部眼部滴（自体血清撕裂，AST）。不幸的是，缺乏对AST准备工作的标准化（通常是在医生的办公室或药房中准备的），并且其存储和管理的挑战对该产品的宽度采用有限。为了解决AST的缺点，我们开发了一种专有方法来制造有望的替代方法：使用合格的血剂供血者（Elate-Oculartm; Ocular-PHPL）的合并血小板收集（PHPL）制备标准化的血小板裂解物。我们认为，对于多种促进角膜愈合的生长因素而富含蛋白的蛋白质，可以富含O-GVHD和其他形式的干眼症患者，而对于治疗O-GVHD和其他形式的干眼症患者，则可以优于restasis或AST。该STTR I期申请由Cambium Medical Technologies LLC提交，该公司由埃默里大学医学院的4位教职员工创立，他们开发了Ocular-Phpl。 Emory将成为该应用程序的分包研究组织。埃默里大学（Emory University）提出了专利申请，以保护我们的PHPL专有制造过程，Cambium拥有该专利和技术的专有权。调查人员此前曾收到FDA CBER的两种IND，用于其他应用PHPL（IND14825-NCT01659762和IND16191- NCT02359929），我们现在正在寻求在HSCT患者中进行I/II阶段的I/II期临床研究。为了支持这些临床研究，我们在此应用中建议首先改善并验证效果和效率曲线，并通过：（i）证明在产生埃拉特 - 核糖产生过程中应用病原体失活（PI）过程的可行性； （ii）在埃拉特 - 核心（+/- PI处理）上进行体外工作以比较产物组成和作用机制； （iii）对具有先前存在的炎症状况或泪液产生不足的动物进行动物毒理学/功效研究（+/- PI治疗）。这些目标的成功完成将使我们能够完成我们的FDA IND应用，并启动I/II期研究（我们将寻求II阶段STTR支持），以证明在患有O-GVHD发病率的患者中，振奋性是安全且良好的耐受性，这是朝着未来商业化的必要步骤。