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（由申请人提供）：眼移植物抗宿主病 (O-GVHD) 是同种异体造血干细胞移植 (HSCT) 的一种特别严重且令人衰弱的并发症，60-90% 的慢性 GVHD 患者会出现 O-GVHD。目前，Restasis（环孢素 A，0.05%）是 FDA 唯一批准治疗 O-GVHD 的处方外用药物。 2012 年，Restasis 用于治疗干眼症的销售额略低于 10 亿美元；然而，Restasis 的治疗效果仅为 15% 左右，并且其使用与 17% 的不良事件发生率相关，缺乏稳健的临床有效性。表明需要替代疗法，许多失败的 HSCT 患者通过使用配制为局部滴眼液的自体血清（自体血清泪液，AST）发现症状得到缓解，但不幸的是，AST 缺乏标准化。制剂（通常在医生办公室或药房制备）及其储存和给药方面的挑战限制了该产品的广泛采用。为了解决 AST 的缺点，我们开发了一种专有方法来制造一种有前途的替代品：使用来自合格献血者的混合血小板集合 (phPL) 制备标准化血小板裂解液（Elate-OulousTM；Ocular-phPL），我们相信 Elate-OulousTM 在治疗血小板减少症方面优于 Restasis 或 AST。患有 O-GVHD 和其他形式干眼症的患者，因为 Elate-OcularTM 富含（与血清相比）多种促进角膜愈合的生长因子，具有强大的抗炎作用，可以减少 GVHD 患者的眼部炎症，并且该 STTR I 期申请由 Cambium Medical Technologies LLC 提交，该公司是一家由埃默里大学医学院的 4 名教员创立的初创公司，他们开发了 Eomy-phPL。该申请的分包研究组织已提交专利申请，以保护我们的 phPL 专有制造工艺，而 Cambium 拥有该专利和技术的专有权。研究人员此前已收到 FDA CBER 的两项 IND 申请。 phPL（IND14825-NCT01659762 和 IND16191-NCT02359929），我们现在正在寻求提交治疗 IND Elate-OcularTM 并在患有 O-GVHD 的 HSCT 患者中进行 I/II 期临床研究 为了支持这些临床研究，我们在本申请中建议首先通过以下方式进一步改进和验证 Elate-OcularTM 的安全性和有效性： (i) 证明在 Elate-OcularTM 生产过程中应用病原体灭活 (PI) 工艺的可行性；(ii) 对 Elate-OcularTM（+/- PI 处理）进行体外工作，以比较产品成分和作用机制； (iii) 在已有炎症或泪液生成不足的动物中使用 Elate-OcularTM（+/- PI 治疗）进行动物毒理学/功效研究，成功完成这些目标将使我们能够完成 FDA IND 申请，并启动 I/II 期研究（我们将为此寻求 II 期 STTR 支持），以证明 Elate-OcularTM 对于患有 O-GVHD 发病的患者是安全的且耐受性良好，这是迈向未来的必要步骤商业化。