Islet Transplant - Costimulatory Blockage with LEA29Y

胰岛移植 - LEA29Y 共刺激阻断

基本信息

批准号：
8146930
负责人：
ANDREW M SHAPIRO
金额：
$ 37.8万
依托单位：
UNIVERSITY OF ALBERTA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2012-08-31
项目状态：
已结题

项目摘要

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）：此次更新申请的临床试验方案旨在提高临床胰岛移植的最新水平。 CIT-04/06/07 试验：CIT-04 试验是一项前瞻性、两中心（埃德蒙顿和埃默里）、开放标签、胰岛移植试点研究，评估不含类固醇的钙调神经磷酸酶抑制剂的安全性和有效性。为患有长期 T1D 且对强化胰岛素治疗无效的受试者免费提供基于贝拉西普的免疫抑制药物。我们相信 CIT-04 研究是将共刺激阻断带到临床胰岛移植实践最前沿的独特机会。参与这项二期研究的两个中心还将使用标准制造和免疫抑制方案进行一项单独的胰岛移植三期研究。第三阶段试验。 CIT-07 方案将具有与本 2 期试验相同的纳入/排除标准和终点指标。为了避免受试者选择上的偏差，符合条件的受试者将在移植前被随机分配，参加该 2 期或多中心 3 期研究。 CIT-06研究将是一项针对1型糖尿病肾移植受者的前瞻性、单臂、多中心临床试验，评估胰岛移植的效果。该研究计划在 CIT-04 中招募总共 20 名受试者接受贝拉西普治疗，埃德蒙顿和埃默里都为该试验提供了患者。提议埃德蒙顿将在 CIT-04 中招收 12 名受试者，埃默里 8 名受试者，总共 20 名。还预计埃德蒙顿将在 CIT-07（不含贝拉西普的对比移植组）中招收 6 名受试者，比例为 2 比 1在埃德蒙顿中心对贝拉西普组进行随机化。预计埃默里大学将在 CIT-07 中招募 8 名受试者，以匹配埃默里大学站点 CIT-04 和 CIT-07 之间的 1 对 1 随机化。我们都将向 CIT-06（肾移植后的胰岛，每个部位至少 4 名受试者）贡献受试者。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着改善当前临床胰岛移植的最新技术。具体来说：CIT-07 的设计包括当前公认的胰岛移植前、移植周围和移植后标准实践。 CIT-07 的结果将用于获得 FDA 生物许可。 CIT-04 将研究一种新型共刺激阻断 (Belatacept)/CellCept 免疫抑制剂方案，以提高维持治疗的安全性/耐受性。 CIT-06将研究CIT对肾移植患者的疗效。 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。