Validation of Amotosalen-HCI for Clinical Use

描述（由申请人提供）：Amotosalen-HCI是Cerus公司拥有的专有补骨脂素化合物，已开发用于输血行业的病原体灭活。阿莫托萨伦- hci在光化学过程中用于灭活血小板浓缩物和新鲜冷冻血浆中的病原体。在过去的5年里，Cerus公司一直在开发另一种需要Amotosalen-HCI的光化学过程——AIIogeneic Cellular Immune Therapy （ACIT）。该项目专注于解决错配干细胞移植中未满足的主要安全需求。ACIT已经获得了美国血液学学会（American Society of Hematology）的几份经典手稿和奖项，并在三个临床试验中进行了研究。第一项，“光化学处理供体t细胞补充在HLA单倍型错配造血干细胞移植中的I期研究”，于1998年12月30日首次向FDA提交。第二项是“光化学处理t细胞补充剂在非亲属供体PBSC移植中的1B期研究”，由国家骨髓供体项目向FDA提交，并于2002年9月30日获得批准。第三项试验“用合成补骨脂素（Amotosalen-HCI）和紫外光（UV照明系统，Cerus）治疗自体EBV+淋巴母细胞样细胞系”已由约翰霍普金斯医学院提交申请，并于2002年6月1日获得FDA批准。我们还收到了使用阿莫托萨伦光化学处理细胞进行新的临床试验的额外请求，以改进干细胞移植、开发疫苗和促进光电泳。ACIT技术满足了未满足的需求。ACIT技术的积极发展需要资金支持，不幸的是，目前的商业环境已经排除了Cerus公司提供足够内部支持的可能性。该I期申请要求Cerus公司开发Amotosalen-HCI的GMP配方所需的资金。先前用于ACIT临床研究的制剂已不再生产，也不再支持。本申请要求进行交叉研究所需的资金，该交叉研究将验证Amotosalen-HCI的新配方，用于临床研究，而不是针对病原体灭活市场。需要进行广泛的稳定性研究以确定Cerus Amotosalen-HCI的充分性。

DESCRIPTION (provided by applicant): Amotosalen-HCI is a proprietary psoralen compound owned by Cerus Corporation, which has been developed for the inactivation of pathogens for the blood transfusion industry. Amotosalen-HCI is used in a photochemical process for the inactivation of pathogens in platelet concentrates and in fresh frozen plasma. AIIogeneic Cellular Immune Therapy (ACIT), another photochemical process requiring Amotosalen-HCI, has been in development at Cerus Corporation for the past 5 years. The program is focused on solving the major unmet need of safety in mismatched stem cell transplantation. ACIT has generated several classic manuscripts and awards from the American Society of Hematology and has been under investigation in the clinic in three trials. The first, "A Phase I Study of Photochemically Treated Donor T-Cell Supplements in HLA Haplotype Mismatched Hematopoietic Stem Cell Transplantation," was first filed with the FDA on 12/30/98. The second, "A Phase 1B Study of Photochemically Treated T-cell Supplements in Unrelated Donor PBSC Transplantation," was filed with the FDA by the National Marrow Donor Program and approved on 9/30/02. The third trial, "Autologous EBV+ Lymphoblastoid Cell Line Treated with Synthetic Psoralen (Amotosalen-HCI) and Ultraviolet A Light (UV Illumination System, Cerus)," has been filed by Johns Hopkins School of Medicine and was approved by the FDA on 61612002. We have received additional requests for new clinical trials using Amotosalen Photochemically Treated cells for the improvement of stem cell transplantation, for the development of vaccines, and for facilitating photophoresis. ACIT technology fulfills an unmet need. ACIT technology needs financial support for its aggressive development, and unfortunately the present business climate has eliminated the possibility that there will be sufficient internal support from Cerus Corporation. This Phase I application requests the funds required for the development of a GMP formulation of Amotosalen-HCI at Cerus Corporation. The previously used formulation for prior ACIT clinical studies is no longer manufactured and can no longer be supported. This application requests the funds needed for a crossover study which will validate a new formulation of Amotosalen-HCI for use in clinical studies not directed at the pathogen inactivation market. Extensive stability studies will be required to determine the adequacy of the Cerus Amotosalen-HCI.