Islet Transplant - Costimulatory Blockage with LEA29Y

胰岛移植 - LEA29Y 共刺激阻断

• 批准号: 7791627
• 负责人: ANDREW M SHAPIRO
• 金额: --
• 依托单位: UNIVERSITY OF ALBERTA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7791627
• 关键词: Arts; Biological; Calcineurin inhibitor; Cellcept; Clinical; Clinical Protocols; Clinical trial protocol document; Enrollment; Exclusion Criteria; Face; Future; Goals; Immunosuppressive Agents; Insulin; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans Transplantation; Kidney Transplantation; LEA29Y; Licensure; Maintenance Therapy; Measures; Multi-Institutional Clinical Trial; Organ Donor; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Pilot Projects; Protocols documentation; Randomized; Refractory; Regimen; Research; Safety; Site; Steroids; Subjects Selections; Transplant Recipients; Transplantation; arm; base; design; improved; islet; novel; open label; phase 2 study; phase 3 study; prospective

DESCRIPTION (provided by applicant): The clinical trial protocols of this renewal application have been designed to improve the state-of-the-art in clinical islet transplantation. CIT-04/06/07 Trials: The CIT-04 trial is a prospective, two-center (Edmonton and Emory), open-label, pilot study of islet transplantation assessing the safety and efficacy of a steroid-free, calcineurin inhibitor-free belatacept based immunosuppressive medication in subjects with long-standing T1D that is refractory to intensive insulin therapy. We believe the CIT-04 study is a unique opportunity to bring co-stimulation blockade to the forefront of clinical islet transplant practice. The two centers participating in this phase 2 study will also undertake a separate, phase 3 study in islet transplantation, using a standard manufacturing and immunosuppressive regimen. The phase 3 trial. Protocol CIT-07, will have inclusion/exclusion criteria and endpoint measures that are identical to those in this phase 2 trial. In order to avoid bias in selection of subjects, eligible subjects will be randomized, prior to transplantation, to participate either in this phase 2 or the multi-center phase 3 study. The CIT-06 study will be a prospective, single-arm, multi-center clinical trial in kidney transplant recipients with T1D, assessing the effect of islet transplantation. The research plan is to enroll a total of 20 subjects in CIT-04 to receive Belatacept with both Edmonton and Emory contributing patients to this trial. It is proposed that Edmonton will enroll 12 subjects in CIT-04 and Emory 8 subjects, for a total of 20. It is also anticipated that Edmonton will enroll 6 subjects in CIT-07 (the comparison transplant group without Belatacept) with 2 to 1 randomization at the Edmonton site towards the Belatacept arm. It is expected that Emory will enroll 8 subjects in CIT-07 to match the 1 to 1 randomization between CIT-04 and CIT-07 at the Emory site. We will both contribute subjects to CIT-06 (islet after kidney transplantation, with at least 4 subjects per site). As part of the CIT consortium, Edmonton's continued participation in these three trials will help refine future islet transplantation therapy. RELEVANCE (taken from the application): The clinical protocols developed by the CIT consortium have been designed to significantly improve the current state-of-the-art in clinical islet transplantation. Specifically: CIT-07 has been designed to include current accepted standard practice in pre, peri and post islet transplantation. Results from CIT-07 will be used to obtain FDA biological licensure. CIT-04 will study a novel co-stimulation blockade (Belatacept)/CellCept immunosuppressant regime to improve safety/tolerability of maintenance therapy. CIT-06 will investigate the efficacy of CIT in kidney transplant patients. The overall goal of the CIT-04/06/07 trials is to improve insulin independence duration of islet transplant patients, most preferred with islets from single donor organs. The combination of the CIT consortium trials will change the face of future clinical islet transplantation therapy.

描述（由申请人提供）： 本更新申请的临床试验方案旨在提高临床胰岛移植的最新技术水平。CIT-04/06/07试验：CIT-04试验是一项关于胰岛移植的前瞻性、双中心（埃德蒙顿和埃默里）、开放标签、初探性研究，旨在评估不含类固醇、不含钙调磷酸酶或贝拉西普的免疫抑制药物在胰岛素强化治疗难治的长期T1 D受试者中的安全性和疗效。我们相信CIT-04研究是一个独特的机会，将共刺激阻断带到临床胰岛移植实践的最前沿。参与这项2期研究的两个中心还将进行一项单独的3期胰岛移植研究，使用标准的生产和免疫抑制方案。第三阶段试验。方案CIT-07的入选/排除标准和终点指标与本II期试验相同。为了避免受试者选择中的偏倚，将在移植前对合格受试者进行随机分配，以参与本II期或多中心III期研究。CIT-06研究将是一项在T1 D肾移植受者中进行的前瞻性、单臂、多中心临床试验，评估胰岛移植的效果。研究计划是在CIT-04中共入组20例受试者接受贝拉西普治疗，其中埃德蒙顿和埃默里均有患者参与本试验。拟定埃德蒙顿在CIT-04中入组12例受试者，Emory入组8例受试者，共计20例。还预计埃德蒙顿将在CIT-07（不含贝拉西普的对照移植组）中入组6例受试者，在埃德蒙顿研究中心按照2：1的比例随机分配至贝拉西普组。预计Emory将在CIT-07中入组8例受试者，以匹配Emory研究中心CIT-04和CIT-07之间的1：1随机分配。我们都将为CIT-06（肾移植后的胰岛，每个研究中心至少4例受试者）提供受试者。作为CIT联盟的一部分，埃德蒙顿继续参与这三项试验将有助于完善未来的胰岛移植疗法。 相关性（摘自申请）：CIT联盟开发的临床方案旨在显著改善临床胰岛移植的当前最新技术水平。具体而言：CIT-07的设计包括胰岛移植前、后和后的当前公认标准实践。CIT-07的结果将用于获得FDA生物许可证。CIT-04将研究一种新型共刺激阻断剂（Belatacept）/CellCept免疫抑制剂方案，以改善维持治疗的安全性/耐受性。CIT-06将研究CIT在肾移植患者中的疗效。CIT-04/06/07试验的总体目标是改善胰岛移植患者的胰岛素依赖性持续时间，最优选来自单一供体器官的胰岛。CIT联盟试验的结合将改变未来临床胰岛移植治疗的面貌。