A Study of Mirikizumab (LY3074828) in Participants With Moderately to Severely Active Ulcerative Colitis

Phase 3

Active, not recruiting

Conditions: Ulcerative Colitis
Ulcerative Colitis Chronic

Interventions: Drug: Mirikizumab

Registration Number: NCT05767021

Lead Sponsor: Eli Lilly and Company

Brief Summary: A study to investigate bowel urgency in adults with moderately to severely active ulcerative colitis (UC) treated with mirikizumab. The study will have 4 periods and will last for 36 weeks.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 172

Inclusion Criteria

Have an established diagnosis of UC for ≥3 months
Have confirmed diagnosis of moderately for severely active UC
Have current bowel urgency
Have demonstrated an inadequate response to, a loss of response to, or an intolerance to conventional or to biologic/Janus Kinase (JAK) inhibitor/sphingosine-1-phosphate (S1P) receptor modulator therapy for UC.

Exclusion Criteria

Have Crohn's disease (CD)
Have inflammatory bowel disease-unclassified, formerly known as indeterminate colitis, or
Have ulcerative proctitis, disease limited to the rectum, that is, distal to the recto-sigmoid junction, which lies approximately 10 to 15 centimeter (cm) from anal verge.
Have an inherited immunodeficiency syndrome or a monogenic cause of UC-like colonic inflammation
Have any history or current evidence of cancer of the gastrointestinal tract
Have active tuberculosis
Have HIV infection.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
300 mg Mirikizumab	Mirikizumab	Participants received 300 milligram (mg) mirikizumab every 4 weeks (Q4W) at week 0, 4, and 8 administered intravenously (IV).

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Bowel Urgency Severity Urgency Numeric Rating Scale (UNRS)	Baseline, Week 12	The UNRS 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. Baseline Observation Carried Forward (BOCF) endpoint was defined as the baseline value for participants discontinued during acute phase and defined as the last non-missing observation in the treatment phase for all other randomized participants.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Bowel Urgency Frequency (BUF)	Baseline, Week 12	BUF is participant reported single item measure of the number of urgent bowel movements reported in the past 24 hours.
Percentage of Participants Achieving Clinically Meaningful Improvement in BUF	Baseline to Week 12	This outcome measures the percentage of participants who experience a clinically meaningful reduction in the frequency of bowel urgency episodes from baseline to the 12 week treatment period. Results for this outcome will be reported during final results posting.
Percentage of Participants With Stool Deferral Time (SDT) Intervals at Week 12	Week 12	The SDT is a participant-reported single item measure of the average duration a patient could delay defecation in the past 24 hours. The shortest weekly SDT is used for analysis of SDT in minutes by taking the shortest response (i.e. minimum value) available over the past 7 days, where no urgency is treated as the largest value. The SDT categories were:\<1 min, ≥1 min to \<2 min, ≥2 min to \<5 min, ≥5 min to \<15 min, and ≥15 min or no urgency. No urgency indicates participant's selected "Did not feel urge to have a bowel movement in the past 24 hours" for all available days in 7-day period.
Percentage of Participants Achieving Both Clinical Remission, Based on the Modified Mayo Score (MMS) and a Rounded Urgency Numeric Rating Scale (UNRS) Score of ≤1	Week 12	Clinical remission based on MMS is defined as Stool Frequency (SF) sub score (range 0-3, higher is worse) = 0, or SF = 1 with a ≥1- point decrease from baseline, and 1. Rectal Bleeding (RB) sub score (range 0-3, higher is worse) = 0, and 2. Endoscopic sub score (ES) (range 0-3, higher is worse) = 0 or 1 (excluding friability). UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency) This outcome assesses the proportion of participants who achieved both a clinical response, as defined by an MMS, and an improvement of ≥3 points from baseline in a UNRS score at Week 12.
Percentage of Participants Achieving Both Clinical Response, Based on the Modified Mayo Score (MMS) and a Rounded Urgency Numeric Rating Scale (UNRS) Score ≥3 Points of Improvement From Baseline	Week 12	Clinical response based on MMS is defined as: 1. A change in the MMS of ≤ -2 points and ≤ -30% change from baseline, and 2. A change of ≤-1 point in the RB subscore (range 0-3, higher is worse) from baseline or a RB score of 0 or 1. UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency) This outcome measures the percentage of participants achieving both, clinical response, based on the MMS, and a UNRS score of ≥3 points of improvement from baseline at 12 weeks.
Correlation Between Change From Baseline in Urgency Numeric Rating Scale (UNRS), Baseline in Bowel Urgency Frequency (BUF), Stool Deferral Time (SDT) and Absorbent Product Use (APU) Measures, With QoL/Functional Outcome Measures and UC Symptom Measures	Baseline, Week 12 UC symptom measures:Patient Global Rating of Severity (PGR-S)(1-6),Patient Global Impression of Change (PGI-C)(1-7),Mayo SF/RB (0-3),Abdominal pain/fatigue NRS (0-10),nocturnal stool frequency; higher=worse severity for all measures.	This outcome evaluates correlations between change from baseline in UNRS, BUF, SDT, APU, and PROs related to quality of life (QoL), functional outcomes, and UC symptoms. QoL is assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ), a 32-item patient-completed tool with four domains: bowel (score range 10-70), systemic (5-35), emotional (12-84), and social (5-35). Each item is rated on a 7-point Likert scale (1 = very severe problem, 7 = not a problem at all); The total IBDQ score is calculated by summing the scores from all four domains and total score range is 32-224 (Higher = better QoL). Functional outcomes measures: Work Productivity and Activity Impairment (WPAI) questionnaire (four scores derived: absenteeism, presenteeism, productivity loss, activity impairment; each score 0-100%, higher = greater impairment) and Generalized Anxiety Disorder-7 (GAD-7;total score range 0-21, higher = more severe anxiety)... (Continued below due to character constraint)
Percentage of Participants Achieving Clinically Meaningful Improvement of SDT	Week 12	This outcome measures the percentage of participants who demonstrate a clinically meaningful improvement in SDT. Results for this outcome will be reported during final results posting.
Pairwise Correlations Between the Urgency Numeric Rating Scale (UNRS), Baseline in Bowel Urgency Frequency (BUF), Stool Deferral Time (SDT) and Absorbent Product Use (APU) Measures	Baseline to Week 12	UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency). BUF measures the number of urgent bowel movements reported in the past 24 hours. SDT measures the average duration a patient could delay defecation in the past 24 hours. APU is a single item to assess participant's need to wear an adult diaper, pad or protection because of bowel urgency. This outcome evaluates the pairwise correlations among four bowel urgency-related measures above.
Pairwise Correlations Between Change From Baseline in Urgency Numeric Rating Scale (UNRS), Baseline in Bowel Urgency Frequency (BUF), Stool Deferral Time (SDT) and Absorbent Product Use (APU) Measures	Baseline, Week 12	UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency). BUF measures the number of urgent bowel movements reported in the past 24 hours. SDT measures the average duration a patient could delay defecation in the past 24 hours. APU is a single item to assess participant's need to wear an adult diaper, pad or protection because of bowel urgency. This outcome evaluates the pairwise correlations between the change in correlations among four bowel urgency-related measures above.
Correlation Between Urgency Numeric Rating Scale (UNRS), Baseline in Bowel Urgency Frequency (BUF),Stool Deferral Time (SDT) and Absorbent Product Use (APU) Measures,With Quality of Life (QoL)/Functional Outcome Measures and UC Symptom Measures	Baseline to Week 12 UC symptom measures:Patient Global Rating of Severity (PGR-S)(1-6),Patient Global Impression of Change (PGI-C)(1-7),Mayo SF/RB (0-3),Abdominal pain/fatigue NRS (0-10),nocturnal stool frequency;higher=worse severity for all measures.	This outcome evaluates correlations between UNRS, BUF, SDT, APU, and patient-reported outcomes (PROs) related to quality of life (QoL), functional outcomes, and UC symptoms. QoL is assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ), a 32-item patient-completed tool with four domains: bowel (score range 10-70), systemic (5-35), emotional (12-84), and social (5-35). Each item is rated on a 7-point Likert scale (1 = very severe problem,7 = not a problem at all); The total IBDQ score is calculated by summing the scores from all four domains and total score range is 32-224 (Higher = better QoL). Functional outcomes measures: Work Productivity and Activity Impairment (WPAI) questionnaire (four scores derived: absenteeism, presenteeism, productivity loss, activity impairment; each score 0-100%, higher = greater impairment) and Generalized Anxiety Disorder-7 (GAD-7; total score range 0-21, higher = more severe anxiety)... (Continued below due to character constraint)

Trial Locations

Locations (120): Dedicated Clinical Research
🇺🇸
Litchfield Park, Arizona, United States
Arizona Digestive Health - Sun City
🇺🇸
Sun City, Arizona, United States
Om Research, LLC
🇺🇸
Lancaster, California, United States
California Medical Research Associates, Inc.
🇺🇸
Northridge, California, United States
Clinical Applications Laboratories, Inc.
🇺🇸
San Diego, California, United States
Medical Research Center of Connecticut, LLC
🇺🇸
Hamden, Connecticut, United States
Central Florida Gastro Research
🇺🇸
Clearwater, Florida, United States
Encore Borland-Groover Clinical Research
🇺🇸
Jacksonville, Florida, United States
Research Associates of South Florida
🇺🇸
Miami, Florida, United States
Advanced Research Associates, LLC
🇺🇸
Miami, Florida, United States
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Dedicated Clinical Research
🇺🇸Litchfield Park, Arizona, United States