A Phase 3b, Randomized, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Re-induction Therapy With Ustekinumab in Patients 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
- 215
- 试验地点
- 103
- 主要终点
- Percentage of Participants With Clinical Response at Week 16
研究概览
简要总结
The primary purpose of this study is to evaluate the efficacy and safety of a single intravenous (IV) re-induction dose of approximately 6 milligram per kilogram (mg/kg) ustekinumab in participants with secondary loss of response (LoR) to subcutaneous (SC) every 8 Weeks (q8w) 90 mg ustekinumab maintenance therapy.
详细描述
This study compares the efficacy and safety of a single weight-tiered based IV re-induction dose of approximately 6 mg/kg ustekinumab versus continuing with regular SC q8w 90 mg ustekinumab administration. It consists of screening (5 weeks); treatment period (Week 0 to 24); and safety follow up visit (20 weeks after last dose). The primary hypothesis is that a single IV re-induction dose of ustekinumab is superior to continuing with regular SC q8w maintenance treatment as measured by clinical response after 16 weeks of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy, 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 be randomly assigned to receive either ustekinumab IV re-induction or regular SC q8w 90 mg ustekinumab injection at baseline in a double dummy design. 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
- 未提供
排除标准
- •Complications of Crohn's disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab
- •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 before baseline (or 8 weeks before baseline for intra-abdominal abscesses) provided 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 identified
- •Any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline
- •A draining (i.e., functioning) stoma or ostomy
- •Received ustekinumab intravenous re-induction after the initial weight-tiered-based IV induction dose of ustekinumab
- •Any known history of shortened frequency of SC dose administration (<q8w) for a secondary loss of response where the participant did not, in the opinion of the treating physician, benefit from the dose interval shortening
研究组 & 干预措施
Group 1: Ustekinumab (IV re-induction)
Participants who experience a secondary loss of response (LoR) to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.
干预措施: Ustekinumab approximately 6 mg/kg (IV) (Drug)
Group 1: Ustekinumab (IV re-induction)
Participants who experience a secondary loss of response (LoR) to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.
干预措施: Placebo (SC) (Drug)
Group 1: Ustekinumab (IV re-induction)
Participants who experience a secondary loss of response (LoR) to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.
干预措施: Ustekinumab 90 mg (SC) Group 1 (Drug)
Group 2: Ustekinumab (Continuous q8w SC maintenance)
Participants who experience a secondary LoR to 90 mg ustekinumab maintenance treatment, administered subcutaneously q8w will receive ustekinumab 90 mg subcutaneously and matching placebo intravenously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.
干预措施: Placebo (IV) (Drug)
Group 2: Ustekinumab (Continuous q8w SC maintenance)
Participants who experience a secondary LoR to 90 mg ustekinumab maintenance treatment, administered subcutaneously q8w will receive ustekinumab 90 mg subcutaneously and matching placebo intravenously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.
干预措施: Ustekinumab 90 mg (SC) Group 2 (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Response at Week 16
时间窗: Week 16
Clinical response was defined as greater than or equal to (\>=) 100-point reduction from baseline in Crohn's disease activity index (CDAI) score or a CDAI score \< 150 points. CDAI is validated multi-item measure of severity of illness derived as weighted sum of 8 different Crohn's disease (CD)-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). The last 4 variables were scored over 7 days by participant on diary card. In general, CDAI score ranges from 0 to approximately 600; higher score=higher disease activities. Participants who had prohibited CD-related surgery, prohibited concomitant medication changes or discontinued study agent due to lack of efficacy or adverse event indicated to be of worsening CD prior to designated analysis timepoint were considered not to be in clinical response, regardless of their CDAI score.
次要结局
- Change From Baseline in Clinical Laboratory Values for Chemistry (Alkaline Phosphatase, Alanine Transaminase [ALT], Aspartate Transaminase [AST])(Baseline, Weeks 8, 16, 24)
- Percentage of Participants With Clinical Remission at Week 8(Week 8)
- Percentage of Participants With Normalization of C-reactive Protein (CRP) and/or Normalization of Fecal Calprotectin (fCal) Concentration at Week 16(Week 16)
- Percentage of Participants With Clinical Response at Week 24(Week 24)
- Percentage of Participants With Normalization of C-reactive Protein (CRP) and/or Normalization of Fecal Calprotectin (fCal) Concentration at Week 24(Week 24)
- Percentage of Participants With Treatment-emergent Infections(From baseline (Week 0) up to Week 36)
- Change From Baseline in Clinical Laboratory Values for Hematology (Hematocrit)(Baseline, Weeks 8, 16, 24)
- Change From Baseline in Clinical Laboratory Values for Hematology (Total White Blood Cell [WBC], Neutrophils, Absolute Lymphocyte, Eosinophils, Platelets)(Baseline, Weeks 8, 16, 24)
- Change From Baseline in Clinical Laboratory Values for Chemistry (Total Bilirubin, Direct Bilirubin, Creatinine)(Baseline, Weeks 8, 16, 24)
- Change From Baseline in Clinical Laboratory Values for Chemistry (Sodium, Potassium, Chloride, Blood Urea Nitrogen [BUN]/Urea, Calcium, Phosphate)(Baseline, Weeks 8, 16, 24)
- Percentage of Participants With Clinical Remission at Week 16(Week 16)
- Percentage of Participants With Clinical Remission at Week 24(Week 24)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From baseline (Week 0) up to Week 36)
- Change From Baseline in Clinical Laboratory Values for Hematology (Hemoglobin) and Chemistry (Albumin, Total Protein)(Baseline, Weeks 8, 16, 24)
- Percentage of Participants With Clinical Response at Week 8(Week 8)
- Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From baseline (Week 0) up to Week 36)
- Percentage of Participants With Treatment-emergent Serious Infections(From baseline (Week 0) up to Week 36)