Phase 2 Trial of Gamunex ( Intravenous Gammaglobulin) for Sickle Cell Acute Pain

方案标题：Gamunex(静脉注射丙种球蛋白)治疗镰刀的第二阶段试验 细胞急性疼痛 首席调查员：迪帕·曼瓦尼 共同调查人员：保罗·S·弗雷内特，帕特里夏·A·施，希勒·科恩，凯瑟琳·德里斯科尔， 维罗妮卡·卡鲁洛 摘要 镰状细胞性贫血是世界上最常见的血液病之一。这个 本病最常见的临床表现是血管闭塞复发。 目前除支持性护理外没有其他治疗方法的发作(“危机”) 止痛药。使用镰状细胞病(SCD)小鼠模型的研究表明 白细胞(WBC)黏附于毛细血管后壁和集合部 小静脉通过与镰刀形红细胞相互作用在血管闭塞中起关键作用 (RBCs)1-3。在寻找这些相互作用的分子机制时，它 发现静脉注射免疫球蛋白(IVIG)对小鼠的免疫功能有深远的影响。 红细胞、白细胞和内皮细胞之间的相互作用，改善小静脉的血流 最重要的是，影响了镰刀鱼的整体生存 细胞小鼠。4，5A试验阶段I双盲安慰剂对照，随机，剂量递增 研究表明，虽然800毫克/公斤的剂量可以安全地服用到 镰状细胞病患者在急性疼痛事件期间，400 mg/kg剂量提供最佳剂量 减少输液相关不良事件的生物标志物和临床疗效。我们 因此，要评估静脉免疫球蛋白(IVIG)在400 mg/kg剂量下在 Montefiore收治的镰状细胞病患者的II期临床研究 血管闭塞危机医学中心(VOC)。 假设： 1)收治的镰状细胞病患者对静脉注射免疫球蛋白400 mg/kg耐受性良好 和VOC一起。 2)IVIG能有效改善镰状细胞病患者的VOC。 具体目标： 1)评价单次静脉注射400 mg/kg Gamunex对小鼠 8~21岁镰状细胞型VOC住院患者的VOC解析 一项随机、双盲、安慰剂对照的第二阶段试验。 2)进一步评价单剂400 mg/kg静脉注射Gamunex的安全性。 8-21岁儿童因镰状细胞VOC住院 3)评估粘连和炎症的生物标志物和继发性临床终点 积分(如阿片类药物总使用量、住院时间和乳酸脱氢酶变化) 参加本研究的受试者)。

Protocol Title: Phase 2 trial of Gamunex (Intravenous Gamma globulin) for Sickle Cell Acute Pain Principal Investigator: Deepa Manwani Co-Investigators: Paul S. Frenette, Patricia A. Shi, Hillel Cohen, Catherine Driscoll, Veronica Carullo ABSTRACT Sickle cell anemia is one of the most common hematologic diseases in the world. The most common clinical manifestation of this disease is the recurrence of vaso-occlusive episodes (“crises”) for which there is currently no therapy other than supportive care and analgesics. Studies using a mouse model of sickle cell disease (SCD) suggest that leukocytes (WBCs) that are adherent to the vessel wall of post-capillary and collecting venules play a key role in vascular occlusion by interacting with sickle eythrocytes (RBCs)1-3. In search for the molecular mechanisms responsible for these interactions, it was found that intravenous immune globulin (IVIG) had a profound effect on the interactions among RBCs, WBCs, and the endothelium, improved blood flow in venules of the cremaster muscle and, most importantly, impacted on the overall survival of sickle cell mice.4,5 A pilot phase I double blind placebo controlled randomized, dose escalation study demonstrated that while doses up to 800mg/kg can be safely administered to sickle cell disease patients during acute pain events, a 400mg/kg dose provided optimal biomarker and clinical efficacy with decreased infusion associated adverse events. We therefore want to evaluate intravenous immune globulin (IVIG) at the 400mg/kg dose in a phase II clinical study in sickle cell disease patients that are admitted to Montefiore Medical Center for vaso-occlusive crisis (VOC). Hypothesis: 1) IVIG at 400mg/kg is well tolerated by patients with sickle cell disease admitted with VOC. 2) IVIG can be effective in ameliorating VOC in patients with sickle cell disease. Specific Aims: 1) To evaluate the effect of a single dose of 400mg/kg of IV Gamunex on time to resolution of VOC in subjects 8-21years of age hospitalized for sickle cell VOC in a randomized, double blind placebo controlled Phase 2 trial. 2) To further evaluate safety of a single dose of 400mg/kg of IV Gamunex in subjects 8-21years of age hospitalized for sickle cell VOC 3) To evaluate biomarkers of adhesion and inflammation and secondary clinical end points (e.g. total opioid use, length of hospitalization and change in LDH) in subjects enrolled on this study).