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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: Mirikizumab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1281 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 18, 2018
Actual Primary Completion Date : January 21, 2021
Estimated Study Completion Date : March 19, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo Intravenous (IV) Every 4 Weeks (Q4W)
Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
 Drug: Placebo
Administered IV
Experimental: 300 Milligram (mg) Mirikizumab IV Q4W
300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
 Drug: Mirikizumab
Administered IV
Other Name: LY3074828
Placebo Comparator: Placebo IV Q4W Maximum Extended Enrollment (ME2)
Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
 Drug: Placebo
Administered IV
Experimental: 300 mg Mirikizumab IV Q4W ME2
300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
 Drug: Mirikizumab
Administered IV
Other Name: LY3074828


Outcome Measures
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Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.


  4. 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.


  5. 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).

  6. 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.


  7. 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).

  8. 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).

  9. 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).

  10. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03518086


Contacts
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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

Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol: AMAN 05 Protocol (a)_Redacted  [PDF] September 12, 2019
Study Protocol: AMAN 05 ME2 Protocol Addenda (5)_Redacted  [PDF] March 19, 2018
Statistical Analysis Plan  [PDF] January 14, 2021

More Information
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03518086    
Other Study ID Numbers: 16591
I6T-MC-AMAN ( Other Identifier: Eli Lilly and Company )
2017-003229-14 ( EudraCT Number )
First Posted: May 8, 2018    Key Record Dates
Results First Posted: February 28, 2022
Last Update Posted: October 27, 2022
Last Verified: October 2022
Individual Participant Data (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
Statistical Analysis Plan (SAP)
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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
Interleukin-23 (IL-23) antibody
IL-23p19
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Mirikizumab
 Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Anti-Ulcer Agents
Gastrointestinal Agents