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A Maintenance Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 2)

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ClinicalTrials.gov Identifier: NCT03524092
Recruitment Status : Recruiting
First Posted : May 14, 2018
Results First Posted : November 25, 2022
Last Update Posted : June 1, 2023
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 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).

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1177 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 19, 2018
Actual Primary Completion Date : November 3, 2021
Estimated Study Completion Date : April 25, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: 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.
 Drug: Placebo SC
Administered SC
Experimental: 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.
 Drug: Mirikizumab SC
Administered SC
Other Name: LY3074828
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.
 Drug: Placebo SC
Administered SC
Loss of Response (LOR) Rescue Period:LOR Cohort-300 mg Miri 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.
 Drug: Mirikizumab IV
Administered IV
Other Name: LY3074828
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.
 Drug: Mirikizumab IV
Administered IV
Other Name: LY3074828
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.
 Drug: Mirikizumab SC
Administered SC
Other Name: LY3074828


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants in Clinical Remission at Week 40 [ Time Frame: 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 :
  1. Percentage of Participants in Endoscopic Remission at Week 40 [ Time Frame: 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).

  2. Percentage of Participants With Histologic Remission at Week 40 [ Time Frame: 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).

  3. Percentage of Participants in Symptomatic Remission at Week 40 [ Time Frame: 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).


  4. Percentage of Participants in Endoscopic Response at Week 40 [ Time Frame: Week 40 ]
    Endoscopic response at week 40 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore.

  5. Percentage of Participants in Clinical Response at Week 40 [ Time Frame: 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).

  6. Change From Baseline to Week 40 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [ Time Frame: 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).

  7. Change From Baseline to Week 40 in Fecal Calprotectin [ Time Frame: 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.

  8. Change From Baseline to Week 40 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) [ Time Frame: 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).

  9. Percentage of Participants Hospitalized for Ulcerative Colitis (UC) [ Time Frame: Week 40 ]
    Percentage of participants hospitalized for UC. Only hospitalizations associated with an adverse event with >=24 hours stay were recorded.

  10. Pharmacokinetics (PK): Clearance of Mirikizumab [ Time Frame: Predose: Weeks 0, 4, 12, 24 and 40 ]
    Clearance of mirikizumab was evaluated.


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:

  • 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.

Exclusion Criteria:

  • 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.
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): NCT03524092


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  [PDF] September 12, 2019
Statistical Analysis Plan  [PDF] October 1, 2021

More Information
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03524092    
Other Study ID Numbers: 16823
I6T-MC-AMBG ( Other Identifier: Eli Lilly and Company )
2017-003238-96 ( EudraCT Number )
First Posted: May 14, 2018    Key Record Dates
Results First Posted: November 25, 2022
Last Update Posted: June 1, 2023
Last Verified: May 2023
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: http://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)
IL-23p19
Inflammatory Bowel Disease
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