A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-04236921 In Subjects With Crohn's Disease Who Are Anti-tnf Inadequate Responders (Andante)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 250
- 试验地点
- 190
- 主要终点
- The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
研究概览
简要总结
This is a proof of concept study to determine the efficacy and safety of a monoclonal antibody with three doses versus placebo. Subjects will be randomized to a treatment and the dose will be delivered subcutaneously twice, 4 weeks apart. All subjects will have moderate to severe refractory Crohn's Disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Subjects must have failed or are intolerant to anti TNFs
- •hsCRP greater or equal to 5.0 mg/L
- •Ulcerations demonstrated by colonoscopy as defined by SES CD assessment performed within 8 weeks of study entry (screening) and able to retrospectively complete the SES-CD or colonoscopy performed during screening
排除标准
- •Pregnant or breastfeeding women
- •Crohn's Disease with active fistulae or abscess
- •History of diverticulitis or symptomatic diverticulosis
- •Abnormality in hematology or chemistry profiles at screening
研究组 & 干预措施
Placebo- SC injection
干预措施: PF-04236921 SC injection (Drug)
Drug Dose level 1 - SC injection
干预措施: PF-04236921 SC injection (Drug)
Drug Dose level 2 - SC injection
干预措施: PF-04236921 SC injection (Drug)
结局指标
主要结局
The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
时间窗: Baseline and Week 8
CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score greater than or equal to (\>=) 0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg
时间窗: Baseline and Week 8
CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 1, that will yield different estimates for placebo for the two different models.
The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
时间窗: Baseline and Week 12
CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).
The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg
时间窗: Baseline and Week 12
CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 3, that will yield different estimates for placebo for the two different models.
次要结局
- The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg(Baseline and Weeks 2, 4, 6, and 10)
- The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg(Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg(Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg(Baseline and Weeks 2, 4, 6, and 10)
- The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg(Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg(Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg(Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg(Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs)(At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40)
- Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs)(At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40)
- Serum PF-04236921 Concentration Over Time(Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40)
- Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs)(Induction period: from Week 0 (Day 1) through Week 12; follow-up period: from Week 12 (or discontinuation from the induction period) through last subject visit (up to 28 weeks after completion of or discontinuation from the 12-week induction period))