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: 6309224
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6309224
• 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是一种病态和潜在的破坏性疾病。 具有炎性和调节活性的细胞因子可能在克罗恩病的持续和可能的炎症起始中发挥作用。 虽然皮质类固醇在改善CD受试者的症状方面非常有效，但类固醇戒断具有挑战性，治疗结束后可能发生早期复发。 存在未满足的对帮助受试者脱离类固醇的治疗的医学需求。 多项研究表明，SCH 52000给药在大量CD受试者人群中安全且耐受性良好。 此外，动物模型支持IL-10用于活动性较低的疾病。本研究的假设是SCH 52000（rHulL-10）是一种用于停用皮质类固醇的克罗恩病类固醇依赖患者的有效治疗方法。具体目标1.主要目的评价皮下注射SCH 52000（rHulL-10）治疗激素依赖性克罗恩病受试者的安全性、耐受性和疗效。* 疗效将被定义为在第16周之前使受试者脱离类固醇并且在28周治疗结束时维持临床缓解（CDAI <150）而不需要额外的显著CD管理的能力。将评价两种剂量的SCH 52000（4.0和8.0 mcg/kg）每日一次（QD）SC注射给药，持续2周，随后每周三次（TIW）给药，持续26周，与安慰剂相比。2.次要目标1。评价SCH 52000在第16周前使受试者停用类固醇的能力。2.评价至治疗失败的时间。 如果受试者在治疗期内发生以下任何一种情况，则将其视为治疗失败：* 第16周前无法停用类固醇。* 需要将类固醇剂量增加至基线以上。* 需要额外的重要治疗来治疗克罗恩病 * 因不良事件而停药。* 第28周时CDAI >150。3.评价SCH 52000对28周治疗结束时和随访第8周时健康相关生活质量（HQL）的影响。4.评估随访第8周的缓解率。 反应将被定义为维持临床缓解（CDAI <150）而不需要额外的显著CD管理的能力。