An Open-Label, Phase 4 Study to Evaluate the Efficacy and Safety of Dual Targeted Therapy With Vedolizumab Intravenous (IV) and Adalimumab Subcutaneous (SC) or Vedolizumab IV and Ustekinumab IV/SC in Moderate to Severe Crohn's Disease (CD)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 100
- 主要终点
- Part A: Percentage of Participants With an Endoscopic Response Based on the Simple Endoscopic Score for (SES-CD) at Week 26
研究概览
简要总结
The main aim of this study is to learn about the effect of treatment with vedolizumab IV (vedolizumab) together with adalimumab or vedolizumab (VDZ) together with ustekinumab (UST) in adults with moderate to severe Crohn's Disease, and the effect of treatment with vedolizumab alone, after the dual targeted treatment.
The study is conducted in two parts. In Part A, participants will receive the dual targeted treatment (vedolizumab together with either adalimumab or ustekinumab). In part B, participants will receive vedolizumab only. Part B will include participants who responded to the treatment in Part A.
Each participant will be followed up for at least 26 weeks after the last dose of treatment.
详细描述
The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderate to severe Crohn's disease who have experienced inadequate response, loss of response or intolerance to either one prior interleukin [IL] antagonist, and no other biologic/small molecule (Group A); one IL antagonist and either one Janus kinase inhibitor (JAKi) or one TNFi (other than adalimumab) [Group B] (Cohort 1) or one prior tumor necrosis factor inhibitor [TNFi] and no other biologic/small molecule (Group C); one TNFi and either 1 JAKi or one IL antagonist (other than UST) (Group D) (Cohort 2). The study will look at the efficacy and safety of dual targeted therapy.
The study will enroll approximately 100 participants. Participants will be assigned to one of the two treatment groups in Part A:
- Part A, Cohort 1: Vedolizumab + Adalimumab
- Part A, Cohort 2: Vedolizumab + Ustekinumab
All participants who achieve therapeutic benefit in Part A will receive vedolizumab IV 300 mg monotherapy from Week 30 until Week 46 in Part B. Participants will be followed for a further 20-week safety follow-up period to Week 72 (or 26 weeks post-last dose of study drug).
This multi-center trial will be conducted in the United States and Canada. The overall time to participate in this study is approximately 76 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a confirmed diagnosis of CD at least 3 months before screening, based on endoscopy results.
- •Has moderately to severely active CD at Screening, defined as an SES-CD >=6 (>=4 if isolated ileal disease).
- •Has demonstrated at least 1 of the following (a, b, or c) to at least 1 IL antagonist or at least 1 tumor necrosis factor (TNF) antagonist, at doses approved for the treatment of CD:
- •Inadequate response after completing the full induction regimen;
- •Loss of response (recurrence of symptoms during scheduled maintenance dosing after prior clinical benefit); or
- •Intolerance (a significant adverse event that precluded further use, including but not limited to serious infection including opportunistic infections, malignancy, infusion-related and hypersensitivity reactions including anaphylaxis, and liver injury).
- •Note: Participants with an inadequate response to >2 classes of advanced therapies or >1 agent in the same class are not eligible. Participants who discontinued a third class of advanced therapy for reasons other than inadequate response may be eligible after discussion with the Medical Monitor.
- •In the investigator's opinion, the participant exhibits a therapeutic benefit at Week 26.
排除标准
- •CDAI score >
- •A current diagnosis of ulcerative colitis or indeterminate colitis.
- •Clinical evidence of an abdominal abscess.
- •Known fistula (other than perianal fistula) or phlegmon.
- •Known perianal fistula with abscess.
- •Ileostomy, colostomy, or severe, or symptomatic stenosis of the intestine.
- •Previous extensive bowel resection with 2 entire segments missing, of the following: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum.
- •Short bowel syndrome.
- •Any planned surgical intervention for CD, except for seton placement for perianal fistula without abscess.
- •History or evidence of adenomatous colonic polyps that have not been removed.
- •History or evidence of colonic mucosal dysplasia.
- •Intolerance or contraindication to ileocolonoscopy.
- •Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency infection).
- •Active or latent tuberculosis (TB), regardless of treatment history.
- •A positive test for hepatitis B virus (HBV) as defined by the presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) test.
- •A positive test for hepatitis C virus (HCV), as defined by a positive hepatitis C virus antibody (HCVAb) test and detectable HCV ribonucleic acid (RNA).
- •Received approved or investigational anti-integrin antibodies (i.e., vedolizumab, natalizumab, efalizumab, etrolizumab, abrilumab [AMG 181], anti- mucosal addressin cell adhesion molecule-1 [MAdCAM-1] antibodies, or rituximab) for the treatment of CD.
- •History of or symptoms of progressive multifocal leukoencephalopathy (PML) in the investigator's opinion. If a participant has symptoms consistent with PML, a PML checklist must be completed and submitted to the PML independent adjudication committee. If the PML IAC deems the participant to have PML, the participant is ineligible.
研究组 & 干预措施
Part A, Cohort 2: Vedolizumab + Ustekinumab
Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then Q8W until Week 22 and ustekinumab IV 520, 390, or 260 mg (weight-based), then SC 90 mg 8 weeks after initial IV dose, then Q8W until Week 24.
干预措施: Vedolizumab (Drug)
Part B: Vedolizumab Monotherapy
Participants who achieve therapeutic benefit in Part A will receive vedolizumab IV 300 mg monotherapy, Q8W from Week 30 until Week 46 and will be followed up to Week 52.
干预措施: Vedolizumab (Drug)
Part A, Cohort 1: Vedolizumab + Adalimumab
Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then every 8 weeks (Q8W) until Week 22 and adalimumab SC 160, 80, and 40 mg at Weeks 0, 2, and 4, respectively, then 40 mg every 2 weeks (Q2W) until Week 26.
干预措施: Adalimumab (Drug)
Part A, Cohort 1: Vedolizumab + Adalimumab
Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then every 8 weeks (Q8W) until Week 22 and adalimumab SC 160, 80, and 40 mg at Weeks 0, 2, and 4, respectively, then 40 mg every 2 weeks (Q2W) until Week 26.
干预措施: Vedolizumab (Drug)
Part A, Cohort 2: Vedolizumab + Ustekinumab
Participants will receive vedolizumab IV 300 mg, at Weeks 0, 2, and 6, then Q8W until Week 22 and ustekinumab IV 520, 390, or 260 mg (weight-based), then SC 90 mg 8 weeks after initial IV dose, then Q8W until Week 24.
干预措施: Ustekinumab (Drug)
结局指标
主要结局
Part A: Percentage of Participants With an Endoscopic Response Based on the Simple Endoscopic Score for (SES-CD) at Week 26
时间窗: At Week 26
Endoscopic response is defined by a \>=50 percent (%) reduction from baseline in the SES-CD. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
Part B: Percentage of Participants With an Endoscopic Response Based on the SES-CD at Week 52
时间窗: At Week 52
Endoscopic response is defined by a \>=50 reduction from baseline in the SES-CD. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease.
次要结局
- Change in PRO2 Score from Week 26 to 52(From Week 26 up to Week 52)
- Percentage of Participants in Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) (CDAI <150) at Week 12, Week 26, and Week 52(At Weeks 12, 26, and 52)
- Percentage of Participants in Clinical Remission at Both Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52(At Weeks 12, 26 and 52)
- Percentage of Participants in Endoscopic Remission (SES-CD 0-2) at Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in Endoscopic Remission at Both Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in Deep Remission at Both Week 26 and Week 52(At Weeks 26 and Week 52)
- Percentage of Participants With a Clinical Response (>=100-point Decrease from Baseline in CDAI Score)(At Weeks 12, 26, and 52)
- Percentage of Participants With Complete Endoscopic Healing(At Weeks 26 and 52)
- Percentage of Participants Using Oral Corticosteroids at Baseline who are in Clinical Remission Based on CDAI Score and had Discontinued Corticosteroids(From Week 26 to Week 52)
- Change in SES-CD from Baseline to Week 26 and Week 52(Baseline, Week 26 and Week 52)
- Percentage of Participants with First CD Exacerbation After 26 Weeks(From Week 26 through Week 52)
- Change in FCP Concentrations from Baseline to Week 12, Week 26, Week 42, and Week 52(Baseline, Weeks 12, 26, 42, and 52)
- Percentage of Participants in Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) (CDAI <150) at Week 12, Week 26, and Week 52(At Weeks 12, 26, and 52)
- Percentage of Participants in Clinical Remission at Both Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52(At Weeks 12, 26 and 52)
- Change in PRO2 Score from Week 26 to 52(From Week 26 up to Week 52)
- Percentage of Participants in Stool Frequency Remission(At Weeks 12, 26, and 52)
- Percentage of Participants in Abdominal Pain Remission(At Weeks 12, 26, and 52)
- Percentage of Participants in Endoscopic Remission (SES-CD 0-2) at Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in Endoscopic Remission at Both Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Week 26 and Week 52(At Weeks 26 and 52)
- Percentage of Participants in Deep Remission at Both Week 26 and Week 52(At Weeks 26 and Week 52)
- Percentage of Participants With a Clinical Response (>=100-point Decrease from Baseline in CDAI Score)(At Weeks 12, 26, and 52)
- Percentage of Participants With Complete Endoscopic Healing(At Weeks 26 and 52)
- Percentage of Participants Using Oral Corticosteroids at Baseline who are in Clinical Remission Based on CDAI Score and had Discontinued Corticosteroids(From Week 26 to Week 52)
- Change in SES-CD from Baseline to Week 26 and Week 52(Baseline, Week 26 and Week 52)
- Change in FCP Concentrations from Baseline to Week 12, Week 26, Week 42, and Week 52(Baseline, Weeks 12, 26, 42, and 52)
- Percentage of Participants with First CD Exacerbation After 26 Weeks(From Week 26 through Week 52)