A Multi-Center, Phase 1, Open-Label Evaluation Of The Effect Of PF-00547659 (Anti Madcam Monoclonal Antibody) On Cerebrospinal Fluid (CSF) Lymphocytes In Volunteers With Crohns Disease Or Ulcerative Colitis Who Are Anti-TNFInadequate Responders (TOSCA)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 49
- 试验地点
- 9
- 主要终点
- Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at Month 3
研究概览
简要总结
Study is designed to show a lack of effect on white blood cells circulating in the spinal fluid.
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
- Basic Science
- 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
- •males and females >=18 and =<75 years
- •For CD subjects: hsCRP > 5 mg/L and Harvey-Bradshaw Index > 8 OR when HBI cannot be determined (ie if stoma is present) or hsCRP < 5mg/L then: active lesions on colonoscopy or flexible sigmoidoscopy or active Crohn's disease on CT or MR enterography
- •For UC subjects: diagnosis of UC > 3 months; must have endoscopy to confirm active disease during screening; total mayo score of 6 to 12 points and moderate to severe disease on endoscopy
排除标准
- •Pregnancy or breastfeeding
- •TB or active enteric infections
- •Entero vesicular fistulae
- •Prior use of natalizumab or vedolizumab
- •Right or left heart failure including symptomatic diastolic dysfunction or unexplained elevation of troponin I (>0.05 ng/mL)
研究组 & 干预措施
Cohort 1
Interventions prior to treatment. Control arm
干预措施: lumbar puncture (Drug)
Cohort 2
Interventions prior to and after 3 monthly injections
干预措施: lumbar puncture (Drug)
结局指标
主要结局
Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at Month 3
时间窗: Baseline, Month 3
The primary CSF endpoint of Cohort 2 was the percent change from baseline in absolute lymphocyte counts in CSF after 3 doses of PF-00547659. The hypothesis for the primary endpoint was evaluated using the CSF evaluable population in Cohort 2. CSF samples were obtained via lumbar puncture and analyzed by FACS for total lymphocyte counts. Lumbar punctures were performed by a highly qualified physician using a 20-22 gauge needle, preferably an atraumatic needle.
Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF)
时间窗: Baseline
The primary CSF endpoint of Cohort 2 was the percent change from baseline in absolute lymphocyte counts in CSF after 3 doses of PF-00547659. The hypothesis for the primary endpoint was evaluated using the CSF evaluable population in Cohort 2. CSF samples were obtained via lumbar puncture and analyzed by fluorescence-activated cell sorting (FACS) for total lymphocyte counts. Lumbar punctures were performed by a highly qualified physician using a 20-22 gauge needle, preferably an atraumatic needle.
次要结局
- Cohorts 1 and 2: Total Number of Participants With Non-Lumbar Puncture (LP) Related Treatment-Emergent Adverse Events (AEs), Withdrawals Due to AEs, and Serious Adverse Events (SAEs) During the 12-week Treatment Period(Baseline up to Week 12)
- Cohorts 1 and 2: Number of Participants Who Developed Anti-Drug Antibodies (ADAs) to PF-00547659(Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal)
- Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity(Baseline till End of Study/Early Withdrawal, up to Week 12)