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）用于镰刀的II期试验 细胞急性疼痛 主要研究者：Deepa Manwani 共同研究者：Paul S.作者声明：A. Shi，Hillel Cohen，Catherine Drivel， 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。的 这种疾病最常见的临床表现是血管闭塞性疾病的复发。 目前除支持性治疗外没有其他治疗的发作（“危象”）， 止痛药使用镰状细胞病（SCD）小鼠模型的研究表明， 白细胞（WBC）粘附在毛细血管后的血管壁上， 微静脉通过与镰状红细胞相互作用在血管闭塞中起关键作用 （红细胞）1-3。为了寻找这些相互作用的分子机制， 发现静脉注射免疫球蛋白（IVIG）对 红细胞、白细胞和内皮细胞之间的相互作用，改善了微静脉中的血流 最重要的是，影响了镰状肌的总体存活率， 细胞小鼠。4，5一个试验性I期双盲安慰剂对照随机化，剂量递增 研究表明，虽然高达800 mg/kg的剂量可以安全地给予 镰状细胞病患者在急性疼痛事件期间，400 mg/kg剂量提供了最佳 生物标志物和临床疗效，减少输注相关不良事件。我们 因此，我们希望在400 mg/kg剂量下评价静脉注射免疫球蛋白（IVIG）， 在Montefiore医院接受的镰状细胞病患者中进行的II期临床研究 血管闭塞危象（VOC）医疗中心。 假设： 1)400 mg/kg IVIG在入院的镰状细胞病患者中耐受良好 VOC的。 2)IVIG可有效改善镰状细胞病患者的VOC。 具体目标： 1)评价单次IV给予400 mg/kg Gamunex对至 8- 21岁因镰状细胞VOC住院的受试者的VOC消退， 一项随机、双盲、安慰剂对照的2期试验。 2)为了进一步评价单次静脉注射Gamunex 400 mg/kg的安全性， 8- 21岁因镰状细胞VOC住院的受试者 3)评价粘连和炎症的生物标志物以及次要临床终点 评分（例如，阿片类药物总使用量、住院时间和LDH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).