A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 624
- 试验地点
- 428
- 主要终点
- Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 12
研究概览
简要总结
The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in participants with moderately and severely active Crohn's disease (CD).
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
- •Confirmed diagnosis of CD for at least 3 months prior to Baseline.
- •Confirmed diagnosis of moderate to severe CD as assessed by stool frequency (SF), abdominal pain (AP) score.
- •Evidence of mucosal inflammation based on the Simplified Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader.
- •Demonstrated an inadequate response or intolerance to any biologic therapy for infliximab, adalimumab, certolizumab pegol, vedolizumab, and ustekinumab.
- •If female, participant must meet the contraception recommendations.
排除标准
- •Participant with a current diagnosis of ulcerative colitis or indeterminate colitis.
- •Participant not on stable doses of CD related antibiotics, oral aminosalicylates, corticosteroids or methotrexate (MTX).
- •Participant with the following ongoing known complications of CD: abscess (abdominal or peri-anal), symptomatic bowel strictures, fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study.
- •Participant with ostomy or ileoanal pouch.
- •Participant diagnosed with conditions that could interfere with drug absorption including but not limited to short gut or short bowel syndrome.
- •Screening laboratory and other protocol pre-specified analyses show abnormal results.
研究组 & 干预措施
Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg
Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received DB upadacitinib 45 mg in Part 1 and did not achieve clinical response at Week 12 were included in this group.
干预措施: Upadacitinib (Drug)
Part 1 (Double-blind): Placebo
Participants received upadacitinib matching placebo tablets, orally, once daily (QD) for 12 weeks during the Double-blind (DB) Induction Period.
干预措施: Matching Placebo for Upadacitinib (Drug)
Part 1 (Double-blind): Upadacitinib 45 mg
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
干预措施: Upadacitinib (Drug)
Part 2 (Open-label): Upadacitinib 45 mg
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Open-label (OL) Induction Period.
干预措施: Upadacitinib (Drug)
Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment (ET) Period. Participants who received placebo in Part 1 and did not achieve clinical response at Week 12 were included in this group.
干预措施: Upadacitinib (Drug)
Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg
Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received OL upadacitinib 45 mg during Part 2 and did not achieve clinical response at Week 12 were included in this group.
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 12
时间窗: Week 12
The CDAI was used to evaluate the activity of Crohn's disease. Clinical remission per CDAI is defined as CDAI \<150. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C).
Number of Participants With Adverse Events
时间窗: From first dose of study drug until 30 days following last dose of study drug (up to approximately 28 weeks)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered causally related to the use of the product.
Percentage of Participants With Endoscopic Response at Week 12
时间窗: Baseline to Week 12
Endoscopic response was defined as greater than 50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline of the induction study (or for participants with an SES-CD of 4 at Baseline of the induction study, at least a 2-point reduction from Baseline), as scored by Central Reviewer. SES-CD is calculated based on the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Results were based on NRI-C.
次要结局
- Percentage of Participants With Clinical Remission Per Patient-Reported Outcomes (PROs) at Week 12(Baseline to Week 12)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score at Week 12(Baseline and Week 12)
- Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 4(Week 4)
- Percentage of Participants Who Discontinued Corticosteroid Use for Crohn's Disease (CD) and Achieved Clinical Remission Per CDAI at Week 12, in Participants Taking Corticosteroids at Baseline(Week 12)
- Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving Clinical Response 100 (CR-100) at Week 2(Baseline to Week 2)
- Percentage of Participants With Endoscopic Remission at Week 12(Baseline to Week 12)
- Percentage of Participants Achieving Clinical Response 100 (CR-100) at Week 12(Baseline to Week 12)
- Percentage of Participants With Hospitalizations Due to Crohn's Disease (CD) During Part 1 (12-week Double-blind Induction Period)(Up to Week 12 in Part 1: Double-blind Induction Period)
- Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs) at Week 12, in Participants With EIMs at Baseline(Week 12)