Efficacy and Safety of Etrasimod Versus Mesalazine in Chinese Adult Patients With Active Ulcerative Colitis: A Multicenter, Randomized, Open-Label, Superiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 320
- 主要终点
- Percentage of participants achieving clinical remission
研究概览
简要总结
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon that causes diarrhea, bleeding, and abdominal pain. Mesalazine (5-aminosalicylic acid) is the current standard first-line treatment for mild-to-moderate UC, but many patients do not respond well enough, and some experience side effects. Etrasimod is an oral, selective sphingosine-1-phosphate (S1P) receptor modulator that helps reduce gut inflammation by keeping immune cells from moving into the intestinal wall. This study will test whether etrasimod works better than mesalazine in Chinese adults with active UC. The study plans to enroll about 320 patients from multiple hospitals across China. Eligible participants are adults aged 18 years or older with active UC, defined by a modified Mayo score of 3 to 6 (including specific endoscopic and bleeding criteria). Both newly diagnosed patients (within the past 4 weeks, with no prior UC treatment) and those who had an inadequate response, intolerance, or non-standard use of conventional therapies-but who have never taken biologics or other small-molecule drugs-may join. Patients will be randomly assigned in a 1:1 ratio to receive either etrasimod 2 mg once daily or mesalazine (starting at 4 g/day for 12 weeks, then at least 2 g/day based on response) for 24 weeks. Randomisation will balance important factors like steroid use and baseline endoscopic severity.
The primary research objective is whether more patients on etrasimod achieve clinical remission at week 24. Clinical remission means no rectal bleeding, normal or near-normal stool frequency, and an endoscopic score of 1 or less (without easy bleeding). The study will also measure other benefits, such as symptom improvement, endoscopic healing, normalisation of blood and stool inflammation markers, bowel ultrasound response, tissue healing, and quality of life using standard questionnaires. Safety will be carefully tracked by recording all adverse events during treatment and follow-up.
This is an open-label study (patients and clinical staff know which drug is given) to reflect real-world practice, but the clinical staff who read the colonoscopy results and tissue samples will not know the treatment assignment. An independent statistician will analyse the results. One interim analysis is planned to check for early evidence of benefit or futility. The study involves 24 weeks of treatment, with visits at baseline, week 6, week 12, and week 24, plus a 4-week safety follow-up.
Sample size calculation indicates that 320 participants (160 per group) will provide 90% power to detect a clinically important difference, accounting for a 30% dropout rate. The primary analysis will compare remission rates between groups, adjusting for the stratification factors. All findings will be published to share knowledge with the medical community and help guide future treatment decisions for UC patients in China.
详细描述
Living with ulcerative colitis (UC) can be very difficult. This chronic gut condition causes repeated bouts of diarrhoea, rectal bleeding, abdominal pain, and extreme tiredness. It often strikes young adults in their 20s and 40s, and it can disrupt work, relationships, and daily life. Over time, persistent inflammation also raises the risk of colon cancer.
Currently, the standard first treatment for mild-to-moderate UC in China is mesalazine (5-ASA), an oral anti-inflammatory drug. While it helps many people, a large number of patients either do not respond well enough, relapse frequently, or cannot tolerate its side effects, such as kidney problems. Stronger drugs like biologics or JAK inhibitors are usually held back until after mesalazine fails. This step-up approach may delay effective disease control and allow gut damage to progress.
Etrasimod is a new type of oral pill that works differently. It gently steers certain immune cells away from the gut by blocking their exit from lymph nodes-like keeping "firefighters" away from the "fire" inside the colon. Because it is taken just once a day and does not require injections, it could be more convenient for long-term use. Global clinical trials have shown that etrasimod helps more patients achieve remission than a placebo, but no large study has directly compared it with mesalazine in Chinese adults.
This study aims to fill that gap. The study will recruit about 320 adults with active UC from multiple hospitals across China. Both individuals who are newly diagnosed (within the last month) and those who have used conventional drugs like mesalazine, steroids, or immune suppressors without enough improvement may join-as long as such individuals have never taken biologics or other small-molecule therapies. Participants will be randomly assigned to one of two groups: one group takes etrasimod 2 mg once daily, and the other takes mesalazine at standard doses. The treatment lasts for 24 weeks.
The core research question focuses on whether etrasimod leads to more patients achieving clinical remission-meaning no rectal bleeding, nearly normal bowel habits, and visible healing of the colon lining seen on a camera test (endoscopy)-compared with mesalazine at 24 weeks. The study will also evaluate many other real-world benefits, such as improvement in daily symptoms, deeper tissue healing (examined under a microscope), normalisation of blood and stool inflammation markers, and better scores on quality-of-life questionnaires that assess mood, work, and social activities. Since this is an open-label study, both patients and attending clinical staff will know which drug is being taken, but the clinical staff who review the endoscopic images and biopsy samples will not know the treatment assignments to ensure objective study results.
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
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 18 years or above.
- •Patients diagnosed with active ulcerative colitis at multiple centers including Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (lead center), defined as having a modified Mayo Score (without physician's global assessment) ranging from 3 to 6 points. If ES = 1 point, RBS ≥ 1 point is required. Patients with proctitis are allowed to be enrolled, provided that the proctitis lesion extends more than 5 cm from the anal verge.
- •Treatment-naive patients at initial visit accounting for no more than 30% of the total sample size; Or patients who have previously received conventional pharmacological therapy (including mesalazine, corticosteroids and immunosuppressants) but have inadequate response, intolerance (excluding mesalazine), or non-standard treatment (including but not limited to insufficient dosage or duration of oral 5-ASA, corticosteroids or immunosuppressants, which shall be determined by the investigator based on individual patient conditions). The proportion of patients receiving combined glucocorticoid therapy at baseline shall not exceed 30% of the total sample size.
- •Voluntarily participate in this study and sign the informed consent form.
排除标准
- •Subjects with contraindications to etrolimod or mesalazine.
- •Previously treated with etrasimod or other biologics and small-molecule drugs.
- •Patients are currently receiving full-dose conventional therapy yet still have active disease, including any one of the following:
- •Treatment with mesalazine (≥3 g/day) for ≥8 weeks; Or continuous treatment with prednisone ≥40 mg/day or equivalent dose for ≥3 days (intravenous administration); Or continuous oral treatment with prednisone >20 mg/day or equivalent dose for ≥2 weeks; or oral azathioprine (≥0.75 mg/kg/day), 6-mercaptopurine (≥0.5 mg/kg/day), methotrexate (≥15 mg/week) for ≥3 months.
- •Recent history of acute severe ulcerative colitis (ASUC), toxic megacolon, etc.
- •Patients with stomas or patients with UC scheduled for inpatient surgical intervention.
- •Pregnant and lactating women.
- •Vulnerable groups excluding the elderly and illiterate, including people with mental illnesses, individuals with cognitive impairment, critically ill patients, etc.
- •Other circumstances where researchers consider participation in this study inappropriate.
结局指标
主要结局
Percentage of participants achieving clinical remission
时间窗: week 24
Proportion of participants achieving clinical remission at Week 24. Clinical remission is defined as meeting all three of the following criteria: (1) rectal bleeding score (RBS) = 0; (2) stool frequency score (SFS) = 0, or SFS = 1 with a decrease of ≥1 point from baseline; and (3) Mayo endoscopic score (ES) ≤ 1 (excluding mucosal friability). RBS and SFS are derived from the modified Mayo score and assessed via participant-reported daily diaries. Endoscopic score is obtained by colonoscopy (sigmoidoscopy), with central independent reading performed by readers blinded to treatment allocation. The assessment window is Week 24 ± 4 weeks. For missing data, non-responder imputation (NRI) is applied, meaning that participants with missing data or who discontinue early are counted as not having achieved remission.
次要结局
- Percentage of Participants Achieving Clinical Response(week 12 and week 24)
- Percentage of Participants Achieving Symptomatic Remission(week 12 and week 24)
- Percentage of Participants Achieving Endoscopic Remission(week 12 and week 24)
- Percentage of Participants Achieving Endoscopic Normalization(week 12 and week 24)
- Percentage of Participants Achieving Normalization of Inflammatory Markers(week 12 and week 24)
- Percentage of Participants Achieving Intestinal Ultrasound Response(week 12 and week 24)
- Percentage of Participants Achieving Histologic and Endoscopic Improvement(week 12 and week 24)
- Percentage of Participants Achieving Mucosal Healing(week 12 and week 24)
- Percentage of Participants Achieving Histologic Remission(week 12 and week 24)
- Percentage of Participants Achieving Health-related Quality of Life(week 12 and week 24)
研究者
Qian Cao
Chief physician
Sir Run Run Shaw Hospital