A Maintenance Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis

Eli Lilly and Company1,328 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,328

Conditions

Ulcerative Colitis

Interventions

Mirikizumab SCDRUG

Administered SC

Mirikizumab IVDRUG

Administered IV

Placebo SCDRUG

Administered SC

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (385)

Outcomes

Primary Outcomes

Percentage of Participants in Clinical Remission at Week 40 (Mirikizumab Induction Responders)

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.

Time frame: Week 40

Secondary Outcomes

Percentage of Participants in Endoscopic Remission at Week 40 (Mirikizumab Induction Responders)

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).

Time frame: Week 40

Percentage of Participants With Histologic Remission at Week 40 (Mirikizumab Induction Responders)

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).

Time frame: Week 40

Percentage of Participants in Symptomatic Remission at Week 40 (Mirikizumab Induction Responders)

Data from ClinicalTrials.gov

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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

...and 375 more locations

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 (Mirikizumab Induction Responders)

Endoscopic response at week 40 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore.

Time frame: Week 40

Percentage of Participants in Clinical Response at Week 40 (Mirikizumab Induction Responders)

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).

Time frame: Week 40

Change From Baseline to Week 40 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score (Mirikizumab Induction Responders)

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).

Time frame: Induction Baseline, Week 40

Change From Baseline to Week 40 in Fecal Calprotectin (Mirikizumab Induction Responders)

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.

Time frame: Induction Baseline, Week 40

Change From Baseline to Week 40 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) (Mirikizumab Induction Responders)

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).

Time frame: Induction Baseline, Week 40

Percentage of Participants Hospitalized for Ulcerative Colitis (UC) (Mirikizumab Induction Responders)

Percentage of participants hospitalized for UC. Only hospitalizations associated with an adverse event with \>=24 hours stay were recorded.

Time frame: Week 40

Pharmacokinetics (PK): Clearance of Mirikizumab

Clearance of mirikizumab was evaluated.

Time frame: Predose: Weeks 0, 4, 12, 24 and 40