A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Arm, Placebo-Controlled Maintenance Study of Mirikizumab in Patients With Moderately to Severely Active Ulcerative Colitis (LUCENT 2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,328
- 试验地点
- 667
- 主要终点
- Percentage of Participants in Clinical Remission at Week 40 (Mirikizumab Induction Responders)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of mirikizumab as maintenance therapy in participants who completed as clinical responders in the prior 12-week induction study LUCENT-1 (NCT03518086).
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
- Double (Participant, Investigator)
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
- •Have completed Study AMAN (NCT03518086), with at least 1 study drug administration and without early termination of study drug.
- •Are willing and able to complete the scheduled study assessments, including endoscopy and daily diary entry.
- •If female, must meet the contraception requirements.
排除标准
- •Participants diagnosed with Crohn's disease or inflammatory bowel disease-unclassified (indeterminate colitis) during the induction study AMAN (NCT03518086).
- •Participants with a bowel resection or other surgery for the treatment of UC during the previous induction study AMAN (NCT03518086), or are likely to require surgery for the treatment of UC during study AMBG.
- •Participants with evidence of colonic dysplasia or have been diagnosed with cancer of the gastrointestinal tract during study AMAN (NCT03518086).
- •Participants diagnosed with clinically important infection including, but not limited to, hepatitis B, hepatitis C, HIV/AIDS, and active tuberculosis (TB) during the induction study AMAN (NCT03518086).
- •Participants who initiate a new prohibited medication during the induction study AMAN (NCT03518086).
- •Participants with certain laboratory abnormalities prior to start of AMBG that would require permanent discontinuation from study drug.
研究组 & 干预措施
Open Label Maintenance: Delayed Responders - 200 mg Miri SC - ME2 Cohort
Participants in the ME2 Cohort who initially did not respond to induction study (LUCENT-1), but responded to extended induction therapy at Week 12 of LUCENT-2 (delayed responders), received 200 mg mirikizumab SC Q4W during open label maintenance period from Week 12 until Week 40 or until early termination (rescue was not available for these participants).
干预措施: Mirikizumab SC (Drug)
Maintenance Period: Miri Induction Responder (IR) - Placebo (PBO) Subcutaneous (SC)
Participants who were responders to blinded mirikizumab (miri) at Week 12 in induction study (LUCENT-1) randomized to withdraw from mirikizumab and start receiving PBO SC every 4 weeks (Q4W) from Week 0 of maintenance study (LUCENT-2) until Week 40 or until loss of response was confirmed.
干预措施: Placebo SC (Drug)
Maintenance Period: PBO IR - PBO SC
Participants who were responders to blinded placebo at Week 12 in induction study (LUCENT-1) continue to receive blinded placebo SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.
干预措施: Placebo SC (Drug)
Extended Induction: Induction Nonresponders - 300mg Miri IV
Participants who were nonresponders to blinded mirikizumab or placebo in induction study (LUCENT-1), received additional 3 doses of open label 300 mg mirikizumab IV Q4W during extended induction period from Week 0 of LUCENT-2 until Week 12.
干预措施: Mirikizumab IV (Drug)
Maintenance Period: Miri IR - PBO SC - ME2 Cohort
Participants in the ME2 Cohort who were responders to blinded mirikizumab (miri) at Week 12 in induction study (LUCENT-1) randomized to withdraw from mirikizumab and start receiving PBO SC every 4 weeks (Q4W) from Week 0 of maintenance study (LUCENT-2) until Week 40 or until loss of response was confirmed.
干预措施: Placebo SC (Drug)
Maintenance Period: PBO IR - PBO SC - ME2 Cohort
Participants in the ME2 Cohort who were responders to blinded placebo at Week 12 in induction study (LUCENT-1) continue to receive blinded placebo SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.
干预措施: Placebo SC (Drug)
Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC
Participants who were responders to blinded mirikizumab at Week 12 in induction study (LUCENT-1) randomized to continue to receive 200 mg mirikizumab SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.
干预措施: Mirikizumab SC (Drug)
Open Label Maintenance: Delayed Responders - 200 mg Miri SC
Participants who initially did not respond to induction study (LUCENT-1), but responded to extended induction therapy at Week 12 of LUCENT-2 (delayed responders), received 200 mg mirikizumab SC Q4W during open label maintenance period from Week 12 until Week 40 or until early termination (rescue was not available for these participants).
干预措施: Mirikizumab SC (Drug)
Maintenance Period: Miri IR - 200 mg Miri SC - ME2 Cohort
Participants in the ME2 Cohort who were responders to blinded mirikizumab at Week 12 in induction study (LUCENT-1) randomized to continue to receive 200 mg mirikizumab SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.
干预措施: Mirikizumab SC (Drug)
Maintenance Period: PBO IR - PBO SC - ME2 Cohort
Participants in the ME2 Cohort who were responders to blinded placebo at Week 12 in induction study (LUCENT-1) continue to receive blinded placebo SC Q4W from Week 0 of LUCENT-2 until Week 40 or until loss of response was confirmed.
干预措施: Mirikizumab IV (Drug)
LOR Rescue Period: LOR Cohort-300 mg Miri IV - ME2 Cohort
Participants in the ME2 Cohort who received blinded PBO SC or blinded 200 mg mirikizumab SC Q4W during maintenance period and experienced a loss of response at or after Week 12, received rescue therapy with open label 300 mg mirikizumab intravenous (IV) Q4W for 3 doses.
干预措施: Mirikizumab IV (Drug)
Loss of Response (LOR) Rescue Period: LOR Cohort-300 mg Miri IV
Participants who received blinded PBO SC or blinded 200 mg mirikizumab SC Q4W during maintenance period and experienced a loss of response at or after Week 12, received rescue therapy with open label 300 mg mirikizumab intravenous (IV) Q4W for 3 doses.
干预措施: Mirikizumab IV (Drug)
Extended Induction: Induction Nonresponders - 300mg Miri IV - ME2 Cohort
Participants in the ME2 Cohort who were nonresponders to blinded mirikizumab or placebo in induction study (LUCENT-1), received additional 3 doses of open label 300 mg mirikizumab IV Q4W during extended induction period from Week 0 of LUCENT-2 until Week 12.
干预措施: Mirikizumab IV (Drug)
结局指标
主要结局
Percentage of Participants in Clinical Remission at Week 40 (Mirikizumab Induction Responders)
时间窗: Week 40
Clinical remission at week 40 is defined as achieving a 9-point modified Mayo score for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability). Stool Frequency Subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); Rectal Bleeding Subscore, based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed); Endoscopy Subscore, based on central reading of colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of mirikizumab and who had a correctly measured Modified Mayo Score at baseline. Participants were analyzed according to the treatment arm to which they were randomized, regardless of the treatment actually received.
次要结局
- Pharmacokinetics (PK): Clearance of Mirikizumab(Predose: Weeks 0, 4, 12, 24 and 40)
- Percentage of Participants in Endoscopic Remission at Week 40 (Mirikizumab Induction Responders)(Week 40)
- Percentage of Participants With Histologic Remission at Week 40 (Mirikizumab Induction Responders)(Week 40)
- Percentage of Participants in Symptomatic Remission at Week 40 (Mirikizumab Induction Responders)(Week 40)
- Percentage of Participants in Endoscopic Response at Week 40 (Mirikizumab Induction Responders)(Week 40)
- Percentage of Participants in Clinical Response at Week 40 (Mirikizumab Induction Responders)(Week 40)
- Change From Baseline to Week 40 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score (Mirikizumab Induction Responders)(Induction Baseline, Week 40)
- Change From Baseline to Week 40 in Fecal Calprotectin (Mirikizumab Induction Responders)(Induction Baseline, Week 40)
- Change From Baseline to Week 40 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) (Mirikizumab Induction Responders)(Induction Baseline, Week 40)
- Percentage of Participants Hospitalized for Ulcerative Colitis (UC) (Mirikizumab Induction Responders)(Week 40)