A Maintenance Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Registration Number
- NCT03524092
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1177
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open Label Maintenance: Delayed Responders - 200 mg Miri SC Mirikizumab 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. Extended Induction: Induction Nonresponders - 300mg Miri IV Mirikizumab 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. Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri IV Mirikizumab IV Participants who received PBO SC or 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. Maintenance Period: Miri IR - 200 Milligram (mg) Miri SC Mirikizumab 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. Maintenance Period: Miri Induction Responder (IR) - Placebo (PBO) Subcutaneous (SC) Placebo 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. Maintenance Period: PBO IR - PBO SC Placebo 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants in Clinical Remission at Week 40 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).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Histologic Remission at Week 40 Week 40 Histologic remission was assessed using the Geboes histologic scoring system developed for assessment of histologic disease activity in ulcerative colitis. Remission was defined as Geboes histological subscore of 0 for grades: 2b (lamina propria neutrophils), and 3 (neutrophils in epithelium), and 4 (crypt destruction), and 5 (erosion or ulceration).
Percentage of Participants in Symptomatic Remission at Week 40 Week 40 Symptomatic remission at week 40 is defined as a Mayo score for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline.
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 seen) to 3 (blood alone passed).Percentage of Participants in Endoscopic Response at Week 40 Week 40 Endoscopic response at week 40 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore.
Percentage of Participants in Endoscopic Remission at Week 40 Week 40 Endoscopic remission at week 40 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) at Week 40. Endoscopy subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).
Change From Baseline to Week 40 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score Induction Baseline, Week 40 The IBDQ is a 32-item participant-completed questionnaire that measures 4 aspects of subjects' lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function. Responses are graded on a 7-point. Likert scale in which 7 denotes "not a problem at all" and 1 denotes "a very severe problem." Scores range from 32 to 224; a higher score indicates a better quality of life. Least square (LS) Mean was calculated using analysis of covariance (ANCOVA) model for post-baseline measures: The ANCOVA model includes: treatment, baseline value, prior biologic or tofacitinib failure (yes/no), clinical remission status (yes/no) at AMAN Week 12, and region (North America/Europe/Other).
Change From Baseline to Week 40 in Fecal Calprotectin Induction Baseline, Week 40 Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Least square (LS) Mean was calculated using ANCOVA model for post-baseline measures: The ANCOVA model includes treatment, baseline value, prior biologic or tofacitinib failure (yes/no), corticosteroid use (yes/no) at AMAN baseline, region (North America/Europe/Other), Clinical Remission status (yes/no) at AMAN Week 12.
Change From Baseline to Week 40 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) Induction Baseline, Week 40 The Urgency NRS is a single participant reported item that measures the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). Higher scores indicate more severe urgency. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), clinical remission status (yes/no) at AMAN Week 12, and region (North America/Europe/Other).
Percentage of Participants in Clinical Response at Week 40 Week 40 Clinical response at week 40 is defined as a decrease in the 9-point modified Mayo score (MMS) \[rectal bleeding, stool frequency and the endoscopic findings\] inclusive of \>= 2 points and \>=30% from baseline with either a decrease of rectal bleeding subscore of \>=1 or rectal bleeding subscore of 0 or 1.The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three subscores: 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration).
Percentage of Participants Hospitalized for Ulcerative Colitis (UC) Week 40 Percentage of participants hospitalized for UC. Only hospitalizations associated with an adverse event with \>=24 hours stay were recorded.
Pharmacokinetics (PK): Clearance of Mirikizumab Predose: Weeks 0, 4, 12, 24 and 40 Clearance of mirikizumab was evaluated.
Trial Locations
- Locations (383)
Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States
Dcr-Pi, Pc
🇺🇸Litchfield Park, Arizona, United States
Maricopa Integrated Health System
🇺🇸Phoenix, Arizona, United States
Physicians Research Group
🇺🇸Tempe, Arizona, United States
Valley Gastroenterology
🇺🇸Arcadia, California, United States
Care Access Research
🇺🇸Berkeley, California, United States
Om Research, LLC
🇺🇸Lancaster, California, United States
California Medical Research Associates
🇺🇸Northridge, California, United States
Clinical Applications Laboratories, Inc.
🇺🇸San Diego, California, United States
UCSF Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
Scroll for more (373 remaining)Digestive Health Specialists of the Southeast🇺🇸Dothan, Alabama, United States