TREATMENT WITH SUBCUTANEOUS RHUIL 10 IN STEROID DEPENDENT CROHNS DISEASE

使用皮下 RHUIL 10 治疗类固醇依赖性克罗恩病

• 批准号: 6308029
• 负责人: BRUCE E SANDS
• 金额: $ 0.06万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6308029
• 关键词: Crohn's disease; artificial immunosuppression; clinical research; drug administration routes; hormone therapy; human subject; human therapy evaluation; immunotherapy; interleukin 10

The purpose of this study is to evaluate the safety, tolerance and efficacy of subcutaneous SCH 52000 (rHuIL-10) in steroid-dependent Crohn's Disease subjects. Efficacy will be defined as the ability to wean off steroids by Week 16 and to maintain clinical remission (CDAI<150) at the end of 28 weeks of treatment without the need for additional significant CD management. Crohn's disease is a chronic inflammatory bowel disease (IBD) that can affect any segment of the GIT. Currently used anti-inflammatory drugs include the use of corticosteroids which inhibit synthesis of almost all cytokines. ALthough corticosteroids are highly effetive in improving symptoms, steroid weaning may be difficult without relapses. Past studies have shown that at least 20% of all Crohn's Disease subjects are cortico-dependent. Interleukin-10 (IL-10) can down-regulate both the secretion and gene transcription of IL-1B and TNF (proinflammatory cytokines) and can hence be used in Crohn's disease for its anti-inflammatory effects. Several human studies have shown that SCH 52000 administration to be safe and well tolerated in a large population of subjects with Crohn's disease. This is a Phase II/III randomized, multicenter, double-blind, placebo-controlled study. Subjects will be randomized (1:1:1) to receive 4.0 or 8 mcg/kg of SCH 52000 or placebo. the randomization will be stratified based on concomitant use of immunosuppressive therapy. SCH 52000 or placebo will be administered via SC injection QD for 2 weeks followed by TIW for 26 weeks. The follow-up phase will be 8 weeks. Subjects will undergo a steroid taper according to protocol and must be weaned off by Week 16. This study will require 9 office visits, 2 scheduled phonecalls from the study coordinator and one solely for blood tests. During the screening visit, informed consent, history and physical examination will be undertaken. In addition, blood, urine and stool tests will be done. An electrocardiogram (EKG) and Chest X-ray (CXR) will also be done unless there were normal within the previous 6 months. For the other visits, the same procedure will be undertaken except no further EKG or CXR will be done. A Quality of life questionnaire will be asked for.

这项研究的目的是评估皮下SCH 52000（RHUIL-10）在类固醇依赖性克罗恩病的受试者中的安全性，耐受性和功效。 功效将定义为在第16周之前断奶类固醇并在治疗28周结束时保持临床缓解（CDAI <150）的能力，而无需额外的重要CD管理。克罗恩病是一种慢性炎症性肠病（IBD），可能影响GIT的任何部分。 目前使用的抗炎药包括使用抑制几乎所有细胞因子的合成的皮质类固醇。 尽管皮质类固醇在改善症状方面具有很高的效率，但如果没有复发，类固醇断奶可能很困难。 过去的研究表明，至少有20％的克罗恩病受试者是皮质依赖的。 白介素10（IL-10）可以下调IL-1B和TNF（促炎性细胞因子）的分泌和基因转录，因此可以用于克罗恩病的抗炎作用。 几项人类研究表明，SCH 52000给药在克罗恩病的大量受试者中具有安全性和耐受性。这是一项II/III期随机，多中心，双盲，安慰剂对照研究。 受试者将被随机（1：1：1）接收4.0或8 mcg/kg SCH 52000或安慰剂。 随机分组将根据免疫抑制疗法的使用进行分层。 SCH 52000或安慰剂将通过SC注入QD进行2周，然后进行TIW 26周。 后续阶段将为8周。受试者将根据方案进行类固醇的锥度，必须在第16周之前断奶。这项研究将需要9次办公访问，研究协调员的2个计划的电话呼叫，另一个仅用于血液检查。 在筛选期间，将进行知情同意，历史和体格检查。 此外，还将进行血液，尿液和粪便检查。 除非在过去6个月内正常，否则心电图（EKG）和胸部X射线（CXR）也将进行。 对于其他访问，将进行相同的程序，除非未进行其他心电图或CXR。 将询问生活质量问卷。