A Multicenter, Randomized, Double-Blind Study to Evaluate Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease and Evidence of Mucosal Ulceration
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 514
- 试验地点
- 143
- 主要终点
- Percentage of Participants Who Achieved Clinical Remission at Week 4
研究概览
简要总结
This study will evaluate higher versus standard adalimumab dosing regimens for induction and maintenance therapy in subjects with moderately to severely active Crohn's Disease and evidence of mucosal ulceration.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 Crohn's disease (CD) for at least 90 days, confirmed by endoscopy during the Screening Period.
- •Active CD with a Crohn's Disease Activity Index (CDAI) despite treatment with oral corticosteroids and/or immunosuppressants.
- •Mucosal ulceration on endoscopy.
排除标准
- •Subject with ulcerative colitis or indeterminate colitis.
- •Subject who has had surgical bowel resections in the past 6 months or is planning resection.
- •Subjects with an ostomy or ileoanal pouch.
- •Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
- •Subject who has short bowel syndrome.
- •Chronic recurring infections or active Tuberculosis (TB).
研究组 & 干预措施
Induction: Standard Induction Dose
Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.
干预措施: Adalimumab (Drug)
Induction: Standard Induction Dose
Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.
干预措施: Placebo (Drug)
Induction: Higher Induction Dose
Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
干预措施: Adalimumab (Drug)
Maintenance: Clinically Adjusted (CA) Regimen
Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.
干预措施: Adalimumab (Drug)
Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM will be determined by protocol-established dose adjustment criteria. Doses will be determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 will receive 40 mg ew.
干预措施: Adalimumab (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Clinical Remission at Week 4
时间窗: Week 4
Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Percentage of Participants With Endoscopic Response at Week 12
时间窗: Week 12
Endoscopic response was scored using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 \[none\] to 3 \[very large\]; ulcerated surface ranging from 0 \[none\] to 3 \[\>30%\]; affected surface ranging from 0 \[none\] to 3 \[\>75%\], and narrowing ranging from 0 \[none\] to 3 \[cannot be passed\]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score \> 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline) at Week 12.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).
Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. Serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. TEAEs: any event that began or worsened in severity after the first dose of study drug in the induction or maintenance study. Events with unknown severity were counted as severe. Events with unknown relationship to study drug were counted as drug-related.
次要结局
- Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12(Week 12)
- Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12(Week 4 and Week 12)
- Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12(Week 12)
- Percentage of Participants With Clinical Remission at Week 12(Week 12)
- Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline(Week 12)
- Percentage of Participants With Endoscopic Remission at Week 12(Week 12)
- Change From Baseline in Fecal Calprotectin Level at Week 4(Baseline, Week 4)
- Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4(Week 4)
- Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4(Week 4)
- Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g and Endoscopic Remission at Week 12(Week 12)
- Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12(Week 12)
- Percentage of Participants With Clinical Response at Week 4(Week 4)
- Percentage of Participants With Clinical Response at Week 12(Week 12)
- Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12(Week 12)
- Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4(Week 4)