An Induction Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)

• ClinicalTrials.gov Identifier: NCT03518086
• Recruitment Status: Recruiting
• First Posted: May 8, 2018
• Results First Posted: February 28, 2022
• Last Update Posted: October 27, 2022
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 4, 2018
• First Posted Date: May 8, 2018
• Results First Submitted Date: January 26, 2022
• Results First Posted Date: February 28, 2022
• Last Update Posted Date: October 27, 2022
• Actual Study Start Date: June 18, 2018
• Actual Primary Completion Date: January 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2022)

Percentage of Participants With Clinical Remission at Week 12 [ Time Frame: Week 12 ]

Clinical remission at week 12 is defined as achieving a modified Mayo score (MMS) subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability), excluding consideration of Physician's Global Assessment (PGA). 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). The confidence interval of 99.875% was chosen to match the significance level.

Original Primary Outcome Measures (submitted: May 4, 2018)

Percentage of Participants in Clinical Remission [ Time Frame: Week 12 ]

Clinical remission based on the modified Mayo Score (MMS).

Current Secondary Outcome Measures (submitted: February 25, 2022)

• Percentage of Participants With Clinical Response at Week 12 [ Time Frame: Week 12 ]
  Clinical response at week 12 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).The MMS ranges from 0 to 9 points,with higher scores representing more severe disease. The confidence interval of 99.875% was chosen to match the significance level.
• Percentage of Participants With Endoscopic Remission at Week 12 [ Time Frame: Week 12 ]
  Endoscopic remission at week 12 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) at Week 12. Endoscopy subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration); The Mayo endoscopic score ranges from 0 to 3 points, with higher scores representing more severe disease. The confidence interval of 99.875% was chosen to match the significance level.
• Percentage of Participants With Symptomatic Remission at Week 12 [ Time Frame: Week 12 ]
  Symptomatic remission at week 12 is defined as a Mayo subscore 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). The confidence interval of 99.875% was chosen to match the significance level.
• Percentage of Participants With Symptomatic Response at Week 12 [ Time Frame: Week 12 ]
  Symptomatic response at week 12 is defined as ≥30% decrease from baseline in the sum of stool frequency and rectal bleeding 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). The sum of stool frequency and rectal bleeding subscores ranges from 0 to 6.
• Percentage of Participants With Histologic Remission at Week 12 [ Time Frame: Week 12 ]
  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 With Endoscopic Response at Week 12 [ Time Frame: Week 12 ]
  Endoscopic response at week 12 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore. The Mayo endoscopic subscore ranges from 0 to 3 points, with higher scores representing more severe disease.
• Change From Baseline to Week 12 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) [ Time Frame: Baseline, Week 12 ]
  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), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).
• Change From Baseline to Week 12 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [ Time Frame: Baseline, Week 12 ]
  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 (Guyatt et al. 1989). 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), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).
• Change From Baseline to Week 12 in Fecal Calprotectin [ Time Frame: Baseline, Week 12 ]
  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 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), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).
• Pharmacokinetics (PK): Clearance of Mirikizumab [ Time Frame: Predose on week 0, week 4, week 8 and post dose on week 0, 4 and 12 ]
  Clearance of mirikizumab was evaluated. Clearance is estimated based on concentration data collected in the time frame of 0-12 weeks.

Original Secondary Outcome Measures (submitted: May 4, 2018)

• Percentage of Participants in Clinical Response [ Time Frame: Week 12 ]
  Clinical response based on the MMS.
• Percentage of Participants in Endoscopic Remission [ Time Frame: Week 12 ]
  Endoscopic remission based on the MMS Endoscopic Subscore (ES).
• Percentage of Participants in Symptomatic Remission [ Time Frame: Week 12 ]
  Symptomatic remission based on MMS Stool Frequency (SF) and Rectal Bleeding (RB) subscores.
• Percentage of Participants in Symptomatic Response [ Time Frame: Week 12 ]
  Symptomatic response based on MMS SF and RB subscores.
• Percentage of Participants with Mucosal Healing [ Time Frame: Week 12 ]
  Mucosal healing based on a histologic disease activity index.
• Percentage of Participants in Endoscopic Response [ Time Frame: Week 12 ]
  Endoscopic response based on the MMS ES.
• Change from Baseline to Week 12 in UC Symptoms: Numeric Rating Scale (NRS) [ Time Frame: Baseline, Week 12 ]
  UC symptoms based on NRS scores.
• Change from Baseline to Week 12 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline, Week 12 ]
  Health Related Quality of Life based on IBDQ score.
• Change from Baseline to Week 12 in Fecal Calprotectin [ Time Frame: Baseline, Week 12 ]
  Change from baseline to Week 12 in fecal calprotectin.
• Pharmacokinetics (PK): Clearance of Mirikizumab [ Time Frame: Weeks 0, 4, 8 and 12: Pre-Dose; Week 0 and 4: Up to 2 hour Post-Dose ]
  Clearance of Mirikizumab

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Induction Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Induction Study of Mirikizumab in Conventional-Failed and Biologic-Failed Patients With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)
• Brief Summary: The purpose of this study is to evaluate the safety and efficacy of Mirikizumab in participants with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to, loss of response, or intolerant to conventional or biologic therapy for UC.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ulcerative Colitis

Intervention

• Drug: Mirikizumab
  Administered IV
  Other Name: LY3074828
• Drug: Placebo
  Administered IV

Study Arms

• Placebo Comparator: Placebo Intravenous (IV) Every 4 Weeks (Q4W)
  Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
  Intervention: Drug: Placebo
• Experimental: 300 Milligram (mg) Mirikizumab IV Q4W
  300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
  Intervention: Drug: Mirikizumab
• Placebo Comparator: Placebo IV Q4W Maximum Extended Enrollment (ME2)
  Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
  Intervention: Drug: Placebo
• Experimental: 300 mg Mirikizumab IV Q4W ME2
  300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
  Intervention: Drug: Mirikizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Actual Enrollment (submitted: February 25, 2022): 1281
• Original Estimated Enrollment (submitted: May 4, 2018): 1160
• Estimated Study Completion Date: March 19, 2024
• Actual Primary Completion Date: January 21, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of UC for at least 3 months prior to baseline.
• Confirmed diagnosis of moderately or severely active UC, as assessed by the modified Mayo score (MMS).
• Demonstrated an inadequate response to, a loss of response to, or an intolerance to conventional or to biologic therapy for UC.
• If female, must meet the contraception requirements.

Exclusion Criteria:

• Participants with a current diagnosis of Crohn's disease or inflammatory bowel disease-unclassified (indeterminate colitis).
• Participants with a previous colectomy.
• Participants with current evidence of toxic megacolon.
• Prior exposure to anti-IL12p40 antibodies (e.g. ustekinumab) or anti-IL-23p19 antibodies (e.g. risankizumab, brazikumab, guselkumab or tildrakizumab).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, China, Croatia, Czechia, Denmark, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Poland, Romania, Russian Federation, Saudi Arabia, Serbia, Slovakia, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Brazil

Administrative Information

• NCT Number: NCT03518086
• Other Study ID Numbers: 16591; I6T-MC-AMAN ( Other Identifier: Eli Lilly and Company ); 2017-003229-14 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: October 2022