A Multi-Center, Open-Label Study of the Fully Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderate to Severe Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Abbott
- 入组人数
- 945
- 试验地点
- 375
- 主要终点
- Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5.
研究概览
简要总结
The purpose of this study is to evaluate the safety of adalimumab for treatment of patients with moderate to severe Crohn's Disease (CD) and to measure the effects of treatment on patient general well-being, health-related quality of life (QoL), fistula healing, CD-related extra-intestinal manifestations, work performance, and overall activity.
详细描述
This is an open-label, multi-center, study designed to evaluate the safety and efficacy of adalimumab on inducing and maintaining clinical remission in subjects with moderate to severe Crohn's Disease.
Approximately 1000 subjects with a diagnosis of moderate to severe Crohn's Disease (Harvey Bradshaw Index score >= 7) will be enrolled at approximately 200 sites within Europe. Enrollment will be dependent on meeting all screening criteria.
Study medication will be administered by subcutaneous injection. At Baseline (Week 0), all subjects will receive a dose of 160 mg adalimumab. At Week 2, all subjects will receive a dose of 80 mg adalimumab. Starting at Week 4, all subjects will begin receiving injections of adalimumab 40 mg every other week and will continue every other week dosing through Week 20 except in the case of disease flare or non-response.
Starting at Week 12, subjects who experience a disease flare (flare is defined by an increase in the Harvey Bradshaw Index >=3 and a total Index score of >=7 when compared to Week 4) or are not responding to adalimumab treatment (non-response is defined as a decrease in the Harvey Bradshaw Index by fewer than 3 points compared to Baseline) will be permitted to increase study therapy to adalimumab 40 mg every week.
If the subject continues to demonstrate a lack of improvement on every week adalimumab therapy, they may be withdrawn from the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of moderate to severe Crohn's Disease confirmed by endoscopy or radiologic evaluation for greater than 4 months (16 weeks)
- •Inadequate response to conventional therapy for Crohn's Disease
- •Subjects >=18 and <=75 years of age and in good health (Investigator discretion) with a recent stable medical history
- •Harvey Bradshaw Index score of 7 or higher
排除标准
- •Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
- •Subject who has had surgical bowel resections within the past 6 months or is planning any resection at any time point while enrolled in the study
- •Female subject who is pregnant or breast-feeding or considering becoming pregnant
- •Previous treatment with adalimumab or previous participation in an adalimumab clinical study
- •Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
- •Subjects with any prior exposure to Tysabri® (natalizumab)
- •Subjects on prednisone >40 mg/day (or equivalent), subjects on budesonide >9 mg/day, or subjects who are taking prednisone and budesonide concurrently at Baseline
结局指标
主要结局
Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5.
时间窗: Week 20 of treatment
5-items that assess general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Score is total of 1) subject well-being (0=very well; 4=terrible); 2) abdominal pain (0=none; 3=severe); 3) diarrhea (number of time per day); 4) abdominal mass (0=none; 3=definite and tender); 5) complications (number). Maximum total score for HBI is not specified, is dependent on number of diarrhea times each day and number of complications. Clinical remission = HBI less than 5. Highest total score at Baseline was 47. Missing data were imputed using non-responder imputation (NRI).
次要结局
- Number of Participants Who Were Responders at Week 20 of Treatment. A Responder Was Defined as a Participant Who Had a Decrease of 3 or More on the HBI.(Week 20 of treatment)
- Number of Participants Who Had a Reduction in Number of Draining Fistulas of at Least 50% From Baseline to Week 20(Week 20 of treatment)
- Number of Participants Who Had Extra-intestinal Manifestations (EIM) at Baseline and Resolution by Week 20.(Week 20 of treatment)
- Mean Change in Total Score of Short Inflammatory Bowel Disease Questionnaire (SIBDQ) From Baseline to Week 20(Week 20 of treatment)
- Mean Change in Percent Work Time Missed Due to Crohn's Disease From Baseline to Week 20 of Treatment(Week 20 of treatment)
- Mean Change in Percent Impairment While Working From Baseline to Week 20 of Treatment(Week 20 of treatment)
- Mean Change in Overall Work Productivity and Activity Impairment Score From Baseline to Week 20(Week 20 of treatment)
- Mean Change in Activity Impairment Score From Baseline to Week 20(Week 20 of treatment)