NCT06257706招募中4 期
An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 304
- 试验地点
- 69
- 主要终点
- Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48
研究概览
简要总结
Transmural healing (TMH) is recognized as a potentially important measure of Crohn's disease (CD) activity but not a formal target. Observational studies suggest that TMH may be associated with better long-term outcomes. The study will evaluate TMH using noninvasive intestinal ultrasound (IUS), a patient-friendly technique that can be performed routinely in clinical practice. The aim of the study is to determine if treating to a target of corticosteroid-free (CS-free) IUS outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving CS-free endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD).
Qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups.
Group 1: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH. Group 2: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.
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
- None
盲法说明
Study participants and investigators will be unblinded to the treatment target group assignment.
Central readers performing the assessment of IUS, endoscopy, and histology assessments will be blinded to treatment target randomization, participant, treatment received, and timepoint which will be used to determine treatment escalation.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 80 years, inclusive, at the time of consent;
- •Moderately to severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease);
- •BWT on IUS of >4.0 mm in the terminal ileum or any colonic segment (excluding the rectum) as assessed by the mean of 2 longitudinal and 2 cross-sectional measurements of the same segment;
- •Biologic-naïve or have previous exposure (within the last 5 years of the screening date) to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic;
- •Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;
- •Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study. Females unable to bear children must have documentation of such in the source records;
- •Able to participate fully in all aspects of this clinical trial;
- •Written informed consent must be obtained and documented.
排除标准
- •Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
- •Previously exposed to 2 or more compounds or classes of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD;
- •Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of >40 mg of prednisone or equivalent at randomization;
- •Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy;
- •Have a CD complication, such as symptomatic strictures in the small bowel with >3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention;
- •Previous extensive colonic resection or missing >2 segments out of 5 (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum), ileorectal anastomosis, or a proctocolectomy;
- •Ostomy or ileoanal pouch;
- •Short bowel syndrome;
- •Fibrotic-only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis;
- •Abscess >2 cm, detected by IUS or endoscopy; participants with draining fistulas are not excluded;
- •Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant's ability to participate fully in the study or would compromise participant safety;
- •Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin);
- •Known HIV or hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required;
- •Known active or latent tuberculosis (TB); if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization;
- •Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
- •Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization;
- •Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab;
- •Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.
- •Unwillingness to withhold protocol-prohibited medications during the trial;
- •Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days prior to randomization;
- •History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures;
- •Prior enrolment in the current study and had received study treatment;
- •Pregnant, lactating, or intending to become pregnant/impregnate a partner before, during, or within 18 weeks after the last dose; or intending to donate ova or sperm during such time period;
- •Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination with a live or live-attenuated vaccine during participation in the study;
- •Any person performing mandatory military service, deprived of liberty, in a residential care setting, or any person who, due to a judicial decision, cannot take part in clinical studies;
- •The person is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).
研究组 & 干预措施
Group 1: Corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission
Other
Group 1 will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH.
干预措施: Vedolizumab (Biological)
Group 2: Corticosteroid-free clinical remission + biomarker remission.
Other
Group 2 will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.
干预措施: Vedolizumab (Biological)
结局指标
主要结局
Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48
时间窗: week 48
Corticosteroid-free is defined as not using corticosteroids at the time of the assessment. Endoscopic remission is defined by a total Simple Endoscopic Score for CD (SES-CD) ≤4 and at least a 2-point reduction versus baseline with no subscore greater than 1 in any individual variable. The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3, with higher scores representing more severe endoscopic disease activity. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis (ranges from 0 to 11), because 3 represents a stenosis through which a colonoscope cannot be passed and therefore, can only be observed once. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points).
次要结局
- Percentage of participants with Corticosteroid-free Transmural healing (TMH)+Endoscopic remission+Clinical remission in group 1 and group 2 at week 48(week 48)
- Percentage of participants with Corticosteroid-free IUS response+Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48(week 48)
- Percentage of participants with Corticosteroid-free Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48(week 48)
- Percentage of participants with Corticosteroid-free endoscopic response+Clinical response in group 1 and group 2 at week 48(week 48)
- Percentage of participants with Corticosteroid-free clinical remission in group 1 and group 2 at Week 14, Week 22 and Week 48.(week 14, week 22 and week 48)
- Percentage of participants with Corticosteroid-free Clinical Response in group 1 and group 2 at week 14, week 22 and week 48(week 14, week 22 and week 48)
- Crohn's Disease Activity Index(CDAI) total score and corresponding change from baseline during follow-up (Week 6, Week 14, Week 22, Week 30, Week 38, Week 48, Week 64, Week 80, Week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Percentage of participants with Corticosteroid-free endoscopic response in group 1 and group 2 at week 48(week 48)
- SES-CD total score and corresponding change from baseline to Week 48 in group 1 and group 2(week 48)
- Percentage of participants with Transmural healing (TMH) in group 1 and group 2 at week 48(week 48)
- Percentage of participants with Intestinal Ultrasound (IUS) response in group 1 and group 2 at Week 48(week 48)
- Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at Week 48 in group 1 and group 2.(week 48)
- Color Doppler signal (CDS) and corresponding change from baseline at Week 48 in group 1 and group 2.(week 48)
- International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at Week 48 in group 1 and group 2(week 48)
- Percentage of participants with Transmural healing (TMH) at week 14, week 22, week 30, week 38, and week 48 in group 1(week 14, week 22, week 30, week 38, week 48)
- Percentage of participants with Intestinal Ultrasound (IUS) response at week 14, week 22, week 30, week 38, and week 48 in group 1(week 14, week 22, week 30, week 38, week 48)
- Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1(week 14, week 22, week 30, week 38, week 48)
- Color Doppler signal (CDS) and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1(week 14, week 22, week 30, week 38, week 48)
- International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1(week 14, week 22, week 30, week 38, week 48)
- Percentage of participants with Histologic remission at week 48 in group 1 and group 2(week 48)
- Percentage of patients with Biomarker response at week 48, week 64, week 80 and week 96 in group 1 and group 2(week 48, week 64, week 80, week 96)
- Percentage of participants with Histologic response at week 48 in group 1 and group 2(week 48)
- Percentage of patients with Biomarker remission at week 48, week 64, week 80 and week 96 in group 1 and group 2(week 48, week 64, week 80, week 96)
- Percentage of participants with C-reactive protein (CRP) response during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Percentage of participants with fecal calprotectin (FCal) response during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Changes in C-reactive protein (CRP) from baseline during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Changes in fecal calprotectin (FCal) from baseline during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- 2-item Patient-Reported Outcome (PRO-2) score and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Symptoms and Impacts Questionnaire for CD (SIQ-CD) score and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Urgency Numerical Rating Score (NRS) and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2(week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96)
- Inflammatory Bowel Disease Questionnaire (IBDQ) score and corresponding changes from baseline during follow-up (Weeks 30, week 48 and week 96) in group 1 and group 2(week 30, week 48, week 96)
- Time to CD-related complication from randomization through Week 96 in group 1 and group 2(from randomization through Week 96)
- Time to each component of CD-related complication in group 1 and group 2(from randomization through Week 96)
- Percentage of participants who switched to an alternate biologic (yes/no) by Week 48 and Week 96(week 48, week 96)
- Exposure-adjusted incidence rates of serious adverse events (SAEs), all adverse events (AEs), and AEs of special interest (AESIs) in group 1 and group 2(up to week 96)
研究者
研究点 (69)
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