SUBCUTANEOUS RHUIL 10 IN SUBJECTS W/ STEROID DEPENDENT CROHNS DISEASE

类固醇依赖性克罗恩病受试者皮下注射 RHUIL 10

• 批准号: 6265660
• 负责人: ALAN L. BUCHMAN
• 金额: $ 1.11万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265660
• 关键词: Crohn's disease; clinical research; corticosteroids; drug administration rate /duration; drug administration routes; drug screening /evaluation; drug tolerance; gastrointestinal disorder chemotherapy; human subject; human therapy evaluation; interleukin 10; longitudinal human study; pharmacokinetics; relapse /recurrence; sign /symptom; weaning

Crohn's Disease (CD) is a chronic inflammatroy bowel disease (IBD) that can affect any segment of the GI tract from mouth to anus. CD is a morbid and potentially devastating disease. Cytokines with their inflammatory, as well as regulatory, activities are likely to play a role in the perpetuation and, possibly, the initiation of inflammation in Crohn's Disease. Although cortiocosteroids are highly effective in improving symptoms in CD subjects, steroid-weaning is challenging and early relapses may occur after the end of treatment. There is an unmet medical need for a therapy to assist in weaning subjects off steroids. Several studies have shown that SCH 52000 administration is safe and well tolerated in a large population of CD subjects. Furthermore, animal models support IL-10 being used in less active disease. The hypothesis of this study is that SCH 52000 (rHulL-10) is a useful therapy for weaning steroid-dependent patients with Crohn's disease from the corticosteroids. SPECIFIC AIMS 1. Primary Aim To evaluate the safety, tolerance and efficacy of subcutaneous SCH 52000 (rHulL-10) in steroid-dependent Crohn's Disease subjects. * Efficacy will be defined as the ability to wean subjects 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. Two doses of SCH 52000 (4.0 and 8.0 mcg/kg) administered once daily (QD) as a SC injection for 2 weeks followed by three times a week (TIW) for 26 weeks vs. placebo will be evaluated. 2. Secondary Aims 1. To evaluate the ability of SCH 52000 to wean subjects off steroids by Week 16. 2. To evaluate the time to treatment failure. The subject will be considered a treatment failure if any of the following occurs during the treatment phase: * The inability to wean steroids by Week 16. * The need to increase the steroid dose above Baseline. * The need for additional significant therapy for the management of Crohn's Disease * Discontinuation due to adverse event(s). * CDAI >150 at Week 28. 3. To evaluate the effect of SCH 52000 on the Health-Related Quality of Life (HQL) at end of 28 weeks of treatment and at Follow-Up Week 8. 4. To evaluate the response rate at Follow-Up Week 8. Response will be defined as the ability to maintain clinical remission (CDAI <150) without the need for additional significant CD management.

克罗恩病 (CD) 是一种慢性炎症性肠病 (IBD)，可影响从口腔到肛门的胃肠道任何部分。 CD 是一种病态且具有潜在破坏性的疾病。 细胞因子及其炎症和调节活性可能在克罗恩病炎症的持续存在和可能的引发中发挥作用。 尽管皮质类固醇对于改善 CD 受试者的症状非常有效，但戒除类固醇具有挑战性，并且治疗结束后可能会出现早期复发。 对于帮助受试者戒掉类固醇的治疗的医疗需求尚未得到满足。 多项研究表明，SCH 52000 给药在大量 CD 受试者中是安全的且耐受性良好。 此外，动物模型支持 IL-10 用于治疗不太活跃的疾病。本研究的假设是 SCH 52000 (rHulL-10) 对于克罗恩病类固醇依赖患者来说是一种有用的疗法。具体目标 1. 主要目标 评估皮下注射 SCH 52000 (rHulL-10) 在类固醇依赖性克罗恩病受试者中的安全性、耐受性和有效性。 * 疗效定义为受试者在第 16 周时戒掉类固醇并在 28 周治疗结束时维持临床缓解 (CDAI <150) 且无需额外的显着 CD 管理的能力。将评估两剂 SCH 52000（4.0 和 8.0 mcg/kg），每天一次（QD）皮下注射，持续 2 周，然后每周 3 次（TIW），持续 26 周，与安慰剂相比。 2. 次要目标 1. 评估 SCH 52000 在第 16 周前让受试者戒掉类固醇的能力。 2. 评估治疗失败的时间。 如果在治疗阶段出现以下任何情况，受试者将被视为治疗失败： * 无法在第 16 周之前戒掉类固醇。 * 需要将类固醇剂量增加到基线以上。 * 需要额外的有效治疗来控制克罗恩病 * 因不良事件而停药。 * 第 28 周时 CDAI >150。 3. 评估 SCH 52000 在治疗 28 周结束时和随访第 8 周时对健康相关生活质量 (HQL) 的影响。 4. 评估随访第 8 周时的缓解率。缓解将被定义为维持临床缓解 (CDAI <150) 的能力，而无需额外的显着 CD 管理。