A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of Oral Ozanimod to Evaluate Efficacy and Long-term Safety in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 198
- 试验地点
- 67
- 主要终点
- Proportion of subjects with clinical response
研究概览
简要总结
Japanese patients with moderate or severe active ulcerative colitis as a subject when ozanimod 0.46 mg or 0.92 mg is orally administered is evaluated about dose response, efficacy and safety with placebo as a control.
详细描述
Following the up to 5-week Screening Period, eligible subjects will be randomized to enter the 12 weeks placebo-controlled Induction Period (IP). Subjects who are responders at Week 12 will continue on their assigned treatment in the 40-week Maintenance Period (MP). Non responders at Week 12 have the option to enter the Open-label Extension (OLE). Subjects who complete the MP will be given the option to participate in the OLE. Subjects that enter the MP and experience disease relapse will also have the option to enter the OLE. The OLE will continue until marketing launch (about 4 years of ozanimod for Ulcerative colitis (UC), or until the Sponsor discontinues the development program.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria for Induction and Maintenance Periods
- •Subject is a Japanese male or female subjects aged 18 to 75 years at the time of signing the informed consent form (ICF) at Screening.
- •Subject has had Ulcerative Colitis (UC) diagnosed at least 3 months prior to first investigational product administration. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report.
- •Subject has evidence of UC extending ≥ 15 cm from the anal verge as determined by Baseline endoscopy (flexible sigmoidoscopy or colonoscopy).
- •Subject has active UC defined as Mayo score of 6 to 12 inclusive, with endoscopic subscore of ≥ 2, a rectal bleeding score of ≥ 1, and a stool frequency score ≥
- •Main Inclusion Criteria for Open-label Extension Period
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Must have completed the Week 12 Visit and is non-responder at Week 12
- •Who completes the IP and enters the MP, completes participation through the last study treatment visit at Week 52 with maintaining clinical response, OR experiences disease relapse during the MP
排除标准
- •Main Exclusion Criteria
- •Subject has severe extensive colitis
- •Subject has diagnosis of Crohn's disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn's disease or microscopic colitis or radiation colitis or ischemic colitis.
- •Subject has positive stool examination for pathogens (ova and parasites, bacteria) or positive test for toxin producing Clostridium difficile (C. difficile) at Screening.
- •Subject is pregnant or breastfeeding
- •5. Subject has clinically relevant cardiovascular conditions
研究组 & 干预措施
0.46 mg ozanimod oral capsule once daily (QD)
It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with 0.23 mg ozanimod, followed by 3 days of treatment with 0.46 mg ozanimod, followed by 0.46 mg ozanimod.
干预措施: Ozanimod (Drug)
0.92 mg ozanimod oral capsule QD
It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with 0.23 mg ozanimod, followed by 3 days of treatment with 0.46 mg ozanimod, followed by 0.92 mg ozanimod.
干预措施: Ozanimod (Drug)
Placebo oral capsule QD
It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with a placebo capsule, followed by 3 days of treatment with two placebo capsules, followed by two placebo capsules.
干预措施: Placebo (Other)
结局指标
主要结局
Proportion of subjects with clinical response
时间窗: At Week 12
Defined as a reduction from Baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from Baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point
次要结局
- Proportion of subjects with clinical remission(At Week 12 and Week 52)
- Proportion of subjects with a clinical response(At Week 9)
- Proportion of subjects with endoscopic improvement(At Week 12 and Week 52)
- Proportion of subjects with mucosal healing(At Week 12 and Week 52)
- Change in the EuroQol-5 Dimension (EQ-5D) from baseline(At Week 12)
- Proportion of subject with clinical response(At week 52)
- Proportion of subjects in remission while off corticosteroids for any length of time(Up to week 52)
- Adverse Event (AE)(From enrollment until at least 75 days after completion of study treatment)