A Study of Mirikizumab (LY3074828) in Participants With Active Crohn's Disease

Eli Lilly and Company191 enrolled

Overview

The purpose of this study is to evaluate the safety and effectiveness of the study drug Mirikizumab in participants with active Crohn's Disease.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

191

Conditions

Crohn's Disease

Interventions

MirikizumabDRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Active Crohn's Disease (CD) as determined by the SES-CD, and participant reported stool frequency and abdominal pain. * Inadequate response or failure to tolerate at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (eg, azathioprine, 6-mercaptopurine, or methotrexate); or prior exposure to biologics for the treatment of CD. Exclusion Criteria: * Have complications of CD such as strictures, stenoses, or any other manifestation for which surgery might be indicated, or that could confound the evaluation of efficacy. * Diagnosis of conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome. * Have had any kind of bowel resection, diversion, or placement of a stoma within 6 months or any other intra-abdominal surgery within 3 months prior to screening. * Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation.

Locations (108)

Outcomes

Primary Outcomes

Percentage of Participants Achieving Endoscopic Response at Week 12

Endoscopic response defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD calculated as sum of 4 variables for 5 bowel segments: (ileum;right,transverse,and left colon;and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; \>2 cm = score 3); extent of ulcerated surface (none = 0; \<10% = 1;10-30% = 2;\>30% = 3);extent of affected surface (none = 0; \<50% = 1;50-75% = 2;\>75% =3); and presence and type of narrowings (none=0; single, can be passed=1; multiple,can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.

Time frame: Week 12

Secondary Outcomes

Percentage of Participants Achieving Endoscopic Remission at Week 12

Endoscopic remission defined as SES-CD of \<4 ileal-colonic or \<2 for isolated ileal disease, and no subscore \>1 at week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: (ileum; right, transverse, and left colon; and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; greater than (\>) 2 cm = score 3); extent of ulcerated surface (none = 0; less than (\<) 10% = 1; 10-30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50-75% = 2; \>75% = 3); and presence and type of narrowings (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.

Time frame: Week 12

Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12

PRO remission is defined as stool frequency (SF) ≤2.5 and abdominal pain (AP) ≤1 and no worse than baseline at week 12. SF captures the number of liquid or very soft stools. AP score is classified as 0=none, 1=mild, 2=moderate, 3=severe.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Longwood Research

Huntsville, Alabama, United States

Del Sol Research Management, LLC

Tucson, Arizona, United States

Valley View Internal Medicine

Garden Grove, California, United States

Ventura Clinical Trials

Ventura, California, United States

Delta Waves Sleep Disorders and Research Center

Colorado Springs, Colorado, United States

Medical Research Center of Connecticut

Hamden, Connecticut, United States

Clinical Research of West Florida

Clearwater, Florida, United States

Wellness Clinical Research

Hialeah Gardens, Florida, United States

University of Miami

Miami, Florida, United States

Vista Health Research

Miami, Florida, United States

...and 98 more locations

Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12

The PGRS is a 1-item patient-rated questionnaire designed to assess the participant's rating of their disease symptom severity over the past 24 hours. Responses are graded on a 6-point scale in which a score of 1 indicates the subject has no symptoms (that is, "none") and a score of 6 indicates that the participant's symptom are "very severe." Least Squares Mean (LS Mean) was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

Time frame: Baseline, Week 12

Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12

The PGRC scale is a patient-rated instrument designed to assess the participant's rating of change in their symptom(s). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the participant's symptom is "very much better," a score of 4 indicates that the participant's symptom has experienced "no change," and a score of 7 indicates that the participant's symptom is "very much worse."

Time frame: Baseline, Week 12

Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12

The IBDQ is a 32-item self-administered questionnaire. The IBDQ has 4 dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). 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. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

Time frame: Baseline, Week 12

Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12

The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0-4 associated with a range over "Not at all" to "Very much" for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

Time frame: Baseline, Week 12

Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains:physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

Time frame: Baseline, Week 12

Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab

Population mean (between-subject coefficient variance \[CV %\]) apparent clearance. Clearance is estimated based on concentration data collected in the time frame of 0-208 weeks.

Time frame: Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion

Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab

Population mean (between-subject coefficient variance \[CV %\]) apparent volume of distribution. Volume of distribution is estimated based on concentration data collected in the time frame of 0-208 weeks.