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

A Phase 2, Multicenter, Randomized, Parallel-Arm, Placebo-Controlled Study of LY3074828 in Subjects With Active Crohn's Disease (SERENITY)

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 Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Mirikizumab

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Ballarat Health Services - Base Hospital
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne
• Belgium
  • Brussel, Belgium, 1070
    • Hospital Universitaire Erasme Brussel
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• Canada
  • Ontario
    • Sudbury, Ontario, Canada, P3C 5K6
      • Sudbury Endoscopy Centre
• Czechia
  • Hradec Kralove, Czechia, 50012
    • Hepato-gastroenterologie HK, s.r.o.
  • Olomouc, Czechia, 779 00
    • Gregar s.r.o.
  • Praha 4 - Krc, Czechia, 140 59
    • Thomayerova nemocnice
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole
  • Zlin, Czechia, 76275
    • Krajska nemocnice T. Bati a.s.
  • Czech Republic
    • Usti nad Labem, Czech Republic, Czechia, 40113
      • Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
• Hungary
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centrum Kft
  • Vac, Hungary, 2600
    • Javorszky Odon Hospital
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Chiba-Ken
    • Sakura-shi, Chiba-Ken, Japan, 285 8471
      • Toho University School of Medicine, Sakura Hospital
  • Fukoka
    • Kitakyusyu-shi, Fukoka, Japan, 802-0077
      • Kitakyushu Municipal Medical Center
  • Fukuoka-Ken
    • Chikushino-shi, Fukuoka-Ken, Japan, 818 8502
      • Fukuoka University Chikushi Hospital
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060 0033
      • Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 892-0846
      • Sameshima Hospital
  • Kanagawa
    • Kamakura-shi, Kanagawa, Japan, 247-0056
      • Gokeikai Ofuna Chuo Hospital
  • Miyagi-Ken
    • Sendai-shi, Miyagi-Ken, Japan, 981 3213
      • Takagi Clinic
  • Osaka-Fu
    • Osaka-shi, Osaka-Fu, Japan, 530-0011
      • Kinshukai Infusion Clinic
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Tokyo Medical and Dental University Hospital
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital
    • Shinjuku-ku, Tokyo, Japan, 169-0073
      • JHCO Tokyo Yamate Medical Center
  • Toyama
    • Toyama-Shi, Toyama, Japan, 930-8550
      • Toyama Prefectural Central Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Nijmegen, Netherlands, 6525
    • Radboud Universitair Medisch Centrum Nijmegen
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
  • Noord Brabant
    • Tilburg, Noord Brabant, Netherlands, 5022 GC
      • St Elisabeth Ziekenhuis
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im. dr J. Biziela
  • Lublin, Poland, 20-362
    • KO-MED Centra Kliniczne Lublin II
  • Poznan, Poland, 60-529
    • SOLUMED Centrum Medyczne
  • Rzeszow, Poland, 35-302
    • Korczowski Bartosz, Gabinet Lekarski
  • Szczecin, Poland, 71-434
    • Twoja Przychodnia-Szczecinskie Centrum Medyczne
  • Warszawa, Poland, 00-632
    • Centrum Zdrowia Matki, Dziecka i Mlodziezy
  • Wroclaw, Poland, 50-449
    • Melita Medical Sp. Z O. O.
• Romania
  • Bucuresti, Romania, 010719
    • SC Med Life SA
  • Timisoara, Romania, 300002
    • S.C Centrul de Gastroenterologie Dr. Goldis S.R.L
  • Bihor
    • Oradea, Bihor, Romania, 410469
      • SC Pelican SRL
• Russian Federation
  • Novosibirsk, Russian Federation, 630091
    • Novosibirsk State Medical University
  • Novosibirsk, Russian Federation, 630117
    • FSBI Scientific Research Inst. of Physyology and Basic Medic
  • Omsk, Russian Federation, 644024
    • Ultramed
  • Perm, Russian Federation, 614068
    • City Clinical Hospital # 2 n.a. Fedor Khristoforovich Gral
  • Pushkin, Russian Federation, 196603
    • Private Medical Institution Evromedservis
  • Samara, Russian Federation, 443001
    • Medical Institute REAVIZ
  • Samara, Russian Federation, 443041
    • NonState Healthcare Institution Central Clinical Hospital
  • St. Petersburg, Russian Federation, 194356
    • Baltic Medicine
  • St. Petersburg, Russian Federation, 195257
    • City Hospital of Saint Martyr Elizabeth
  • St. Petersburg, Russian Federation, 196143
    • LLC Scientific Research Centre EKO-Bezopasnost
  • Ulyanovsk, Russian Federation, 432063
    • Ulyanovsk Regional Clinical Hospital
• Switzerland
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich
• Ukraine
  • Kyiv, Ukraine, 02091
    • Kyiv Municipal Clinical Hospital #1
  • Kyiv, Ukraine, 04107
    • Communal institution of the Kyiv Regional Council "Kyiv Regional Clinical Oncology Dispensary"
  • Lviv, Ukraine, 79010
    • Lviv Regional Central Hospital
  • Odesa, Ukraine, 65117
    • Odesa Regional Clinical Hospital
  • Uzhgorod, Ukraine, 88018
    • A. Novak Transcarpathian Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21030
    • SRI of Invalid Rehabil.,Educ.Scient.Med.Complex
  • Vinnytsya, Ukraine, 21005
    • Vinnitsa City Clinical Hospital #1
  • Zaporizhzhia, Ukraine, 69035
    • City Clinical Hospital #6
  • Zaporizhzhia, Ukraine, 69104
    • CI City Hospital #1
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Longwood Research
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Del Sol Research Management, LLC
  • California
    • Garden Grove, California, United States, 92843
      • Valley View Internal Medicine
    • Ventura, California, United States, 93003
      • Ventura Clinical Trials
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves Sleep Disorders and Research Center
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Hialeah Gardens, Florida, United States, 33012
      • Wellness Clinical Research
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33176
      • Vista Health Research
    • Orlando, Florida, United States, 32801
      • Clinical NeuroScience Solutions Inc
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Robley Rex VAMC
    • Owensboro, Kentucky, United States, 42303
      • Health Quest Medical Care
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners LLC
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center
  • Maryland
    • Rosedale, Maryland, United States, 21237
      • Medstar Health Research Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Systems
    • Ypsilanti, Michigan, United States, 48197
      • Huron Gastroenterology Associates
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology, P.A.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical School
    • Saint Louis, Missouri, United States, 63128
      • St. Louis Center for Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Medical Research
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Great Neck, New York, United States, 11021
      • NYU Langone Long Island Clinical Research Associates
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Greenville, North Carolina, United States, 27834
      • Carolina Digestive Diseases
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Health Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultant
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Ocean State Clinical Research Partners
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Union City, Tennessee, United States, 38261
      • Advanced Gastroenterology
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Houston, Texas, United States, 77004
      • Hermann Drive Surgical Hospital
    • Richardson, Texas, United States, 75082
      • Digestive Health Associates of Texas
    • San Antonio, Texas, United States, 78229
      • San Antonio Gastroenterology
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Care Access Research - Salt Lake City
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98195-6424
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mirikizumab; Period 1 (Weeks 0 -12): 200 Milligram (mg), 600 mg, and 1000 mg mirikizumab administered intravenously (IV) every 4 Weeks (Q4W). Period 2 (Weeks 12 - 52): 200 mg, 600 mg, and 1000 mg mirikizumab administered IV Q4W; 300 mg mirikizumab administered subcutaneously (SC) Q4W; 1000 mg mirikizumab administered IV Q4W for non-improvers in period 1; and 1000 mg mirikizumab administered IV Q4W for participants on placebo during period 1. Period 3 (Weeks 52 - 208): 300 mg mirikizumab administered SC Q4W.	Drug: Mirikizumab; Other Names: LY3074828
Placebo Comparator: Placebo; Period 1 (Weeks 0 -12): Participants received placebo administered intravenously (IV) Q4W.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Week 12
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.	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."	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.	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.	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.	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.	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.	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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Sands BE, Peyrin-Biroulet L, Kierkus J, Higgins PDR, Fischer M, Jairath V, Hirai F, D'Haens G, Belin RM, Miller D, Gomez-Valderas E, Naegeli AN, Tuttle JL, Pollack PF, Sandborn WJ. Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease. Gastroenterology. 2022 Feb;162(2):495-508. doi: 10.1053/j.gastro.2021.10.050. Epub 2021 Nov 5.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2016
• Primary Completion (Actual): December 11, 2018
• Study Completion (Actual): February 5, 2021

Study Registration Dates

• First Submitted: September 1, 2016
• First Submitted That Met QC Criteria: September 1, 2016
• First Posted (Estimate): September 7, 2016

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: inflammatory bowel disease; biologic; IL-23
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Anti-Ulcer Agents; Mirikizumab
• Other Study ID Numbers: 16492; I6T-MC-AMAG (Other Identifier: Eli Lilly and Company); 2016-002204-84 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)