A Phase 3b, Multicenter, Randomized, Blinded, Active-Controlled Study to Compare the Efficacy and Safety of Ustekinumab to That of Adalimumab in the Treatment of Biologic Naïve Subjects With Moderately-to-Severely Active Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 386
- 试验地点
- 180
- 主要终点
- Percentage of Participants With Clinical Remission at Week 52
研究概览
简要总结
The purpose of this study is to compare the efficacy of treatment with ustekinumab or adalimumab in biologic naive participants with moderately-to-severely active Crohn's disease (CD) who have previously failed or were intolerant to conventional therapy (corticosteroids and/or immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate), as measured by clinical remission at one year.
详细描述
This study compares the safety and efficacy of ustekinumab versus adalimumab. It will consist of screening (within 1- 5 weeks prior to Week 0), treatment phase (Weeks 0 to 52), and follow-up phase (up to Week 76). The primary hypothesis is that ustekinumab is superior to adalimumab as measured by clinical remission after one year of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy; CD-related healthcare utilization; patient-reported outcomes (PROs); laboratory evaluations; biomarkers; review of concomitant medications and adverse events (AEs); and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants will randomly be assigned to receive either ustekinumab or adalimumab. No participants will be treated with placebo only.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has Crohn's Disease (CD) or fistulizing CD of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, and/or endoscopy
- •Has moderately-to-severely active CD with a baseline Crohn's disease activity index (CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450
- •Has one or more ulceration on screening ileocolonoscopy (which by definition, would result in an Simple Endoscopic Score for Crohn's Disease [SES-CD] of at least 3)
- •Has failed or was intolerant to conventional therapy (corticosteroids, azathioprine [AZA], 6-mercaptopurine [6-MP] and/or methotrexate [MTX]) at adequate doses or is corticosteroid dependent
- •Has not previously received an approved biologic for Crohn's Disease (i.e., infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or approved biosimilars of these agents)
- •Participants on oral corticosteroids (e.g., prednisone, budesonide) at a prednisone-equivalent dose of <=40 or milligram/day (mg/day) or <=9 mg/day of budesonide are budesonide <=9 mg/day are permitted if doses are stable for 3 weeks prior to baseline
- •Participants on AZA, 6-MP, or MTX at screening (or recently prior), must discontinue these medications at least 3 weeks prior to baseline
排除标准
- •Has complications of CD that are likely to require surgery or would confound the ability to assess the effect of ustekinumab or adalimumab treatment using the CDAI, such as: active stoma; short-gut syndrome and severe or symptomatic strictures or stenosis
- •Currently has, or is suspected to have, an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior for intra-abdominal abscesses, if there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present
- •Has had any kind of bowel resection within 6 months prior to baseline or other intra-abdominal surgery or a hospital admission for bowel obstruction within 3 months prior to baseline
- •Has a stool culture or other examination positive for an enteric pathogen, including Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen
- •Has received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 2 weeks of baseline
- •Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or infected skin wounds or ulcers
研究组 & 干预措施
Group 1 (Ustekinumab)
Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram [mg/kg]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals.
干预措施: Placebo for Ustekinumab (Biological)
Group 1 (Ustekinumab)
Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram [mg/kg]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals.
干预措施: Ustekinumab (6 mg/kg) (Biological)
Group 1 (Ustekinumab)
Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram [mg/kg]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals.
干预措施: Ustekinumab (90 mg) (Biological)
Group 2 (Adalimumab)
Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w.
干预措施: Placebo for Adalimumab (Biological)
Group 2 (Adalimumab)
Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w.
干预措施: Adalimumab (40 mg) (Biological)
结局指标
主要结局
Percentage of Participants With Clinical Remission at Week 52
时间窗: Week 52
Percentage of participants with clinical remission at Week 52 were assessed. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than (\<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
次要结局
- Percentage of Participants in Patient Reported Outcome (PRO)-2 Symptom Remission at Week 52(Week 52)
- Percentage of Participants With Clinical Response Through Week 52(Weeks 2, 8, 16, 24, 32, 40, 48, and 52)
- Percentage of Participants With Clinical Remission Through Week 52(Weeks 2, 8, 16, 24, 32, 40, 48, and 52)
- Percentage of Participants With Serious Adverse Events (SAEs)(Up to Week 52 and up to Week 76)
- Percentage of Participants With Clinical Response at Week 52(Week 52)
- Percentage of Participants With Adverse Events (AEs)(Up to Week 52 and up to Week 76)
- Percentage of Participants With Corticosteroid-free Remission at Week 52(Week 52)
- Percentage of Participants With Endoscopic Remission at Week 52(Week 52)
- Percentage of Participants With Durable Clinical Remission at Week 52(Week 52)
- Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52(Weeks 2, 8, 16, 24, 32, 40, 48, and 52)
- Percentage of Participants With Clinical and Biomarker Remission at Weeks 8, 16 and 52(At Weeks 8, 16 and 52)
- Percentage of Participants With Infections(Up to Week 52 and up to Week 76)
- Percentage of Participants With Anti-drug Antibodies(Up to Week 52)
- Percentage of Participants With Clinical Remission at Week 16(Week 16)
- Percentage of Participants With Durable Clinical Response at Week 52(Week 52)
- Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52(Weeks 2, 8, 16, 24, 32, 40, 48, and 52)
- Percentage of Participants With Serious Infections(Up to Week 52 and up to Week 76)