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

Crohn's Disease Clinical Trial

— SERENITY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02891226
• Other study ID #: 16492
• Secondary ID: I6T-MC-AMAG2016-
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2016
• Est. completion date: February 5, 2021

Study information

• Verified date: August 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: February 5, 2021
• Est. primary completion date: December 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Mirikizumab

• Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Ballarat Health Services - Base Hospital	Ballarat	Victoria
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Hospital Universitaire Erasme Brussel	Brussel
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Sudbury Endoscopy Centre	Sudbury	Ontario
Czechia	Hepato-gastroenterologie HK, s.r.o.	Hradec Kralove
Czechia	Gregar s.r.o.	Olomouc
Czechia	Thomayerova Nemocnice	Praha 4 - Krc
Czechia	Fakultni Nemocnice v Motole	Praha 5
Czechia	Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem, o.z.	Usti nad Labem	Czech Republic
Czechia	Krajska nemocnice T. Bati a.s.	Zlin
Hungary	Obudai Egeszsegugyi Centrum Kft	Budapest
Hungary	Javorszky Odon Hospital	Vac
Japan	Tokyo Medical And Dental University Hospital	Bunkyo-ku	Tokyo
Japan	Fukuoka University Chikushi Hospital	Chikushino-shi	Fukuoka-Ken
Japan	Fukuoka University Hospital	Fukuoka
Japan	Sameshima Hospital	Kagoshima-shi	Kagoshima
Japan	Gokeikai Ofuna Chuo Hospital	Kamakura-shi	Kanagawa
Japan	Kitakyushu Municipal Medical Center	Kitakyusyu-shi	Fukoka
Japan	Kyorin University Hospital	Mitaka	Tokyo
Japan	Kinshukai Infusion Clinic	Osaka-shi	Osaka-Fu
Japan	Toho University School of Medicine, Sakura Hospital	Sakura-shi	Chiba-Ken
Japan	Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital	Sapporo-shi	Hokkaido
Japan	Takagi Clinic	Sendai-shi	Miyagi-Ken
Japan	JHCO Tokyo Yamate Medical Center	Shinjuku-ku	Tokyo
Japan	Toyama Prefectural Central Hospital	Toyama-Shi	Toyama
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Radboud Universitair Medisch Centrum Nijmegen	Nijmegen
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	St Elisabeth Ziekenhuis	Tilburg	Noord Brabant
Poland	Szpital Uniwersytecki nr 2 im. dr J. Biziela	Bydgoszcz
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	SOLUMED Centrum Medyczne	Poznan
Poland	Korczowski Bartosz, Gabinet Lekarski	Rzeszow
Poland	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin
Poland	Centrum Zdrowia Matki, Dziecka i Mlodziezy	Warszawa
Poland	Melita Medical Sp. Z O. O.	Wroclaw
Romania	SC Med Life SA	Bucuresti
Romania	SC Pelican SRL	Oradea	Bihor
Romania	S.C Centrul de Gastroenterologie Dr. Goldis S.R.L	Timisoara
Russian Federation	FSBI Scientific Research Inst. of Physyology and Basic Medic	Novosibirsk
Russian Federation	Novosibirsk State Medical University	Novosibirsk
Russian Federation	Ultramed	Omsk
Russian Federation	City Clinical Hospital # 2 n.a. Fedor Khristoforovich Gral	Perm
Russian Federation	Private Medical Institution Evromedservis	Pushkin
Russian Federation	Medical Institute REAVIZ	Samara
Russian Federation	NonState Healthcare Institution Central Clinical Hospital	Samara
Russian Federation	Baltic Medicine	St. Petersburg
Russian Federation	City Hospital of Saint Martyr Elizabeth	St. Petersburg
Russian Federation	LLC Scientific Research Centre EKO-Bezopasnost	St. Petersburg
Russian Federation	Ulyanovsk Regional Clinical Hospital	Ulyanovsk
Switzerland	Universitätsspital Zürich	Zürich
Ukraine	Communal institution of the Kyiv Regional Council "Kyiv Regional Clinical Oncology Dispensary"	Kyiv
Ukraine	Kyiv Municipal Clinical Hospital #1	Kyiv
Ukraine	Lviv Regional Central Hospital	Lviv
Ukraine	Odesa Regional Clinical Hospital	Odesa
Ukraine	A. Novak Transcarpathian Regional Clinical Hospital	Uzhgorod
Ukraine	SRI of Invalid Rehabil.,Educ.Scient.Med.Complex	Vinnytsia
Ukraine	Vinnitsa City Clinical Hospital #1	Vinnytsya
Ukraine	CI City Hospital #1	Zaporizhzhia
Ukraine	City Clinical Hospital #6	Zaporizhzhia
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	Texas Clinical Research Institute, LLC	Arlington	Texas
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Consultants For Clinical Research	Cincinnati	Ohio
United States	Clinical Research of West Florida	Clearwater	Florida
United States	University Hospitals Health Center	Cleveland	Ohio
United States	Delta Waves Sleep Disorders and Research Center	Colorado Springs	Colorado
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Valley View Internal Medicine	Garden Grove	California
United States	Gastro One	Germantown	Tennessee
United States	NYU Langone Long Island Clinical Research Associates	Great Neck	New York
United States	Carolina Digestive Diseases	Greenville	North Carolina
United States	Medical Research Center of Connecticut	Hamden	Connecticut
United States	Wellness Clinical Research	Hialeah Gardens	Florida
United States	Hermann Drive Surgical Hospital	Houston	Texas
United States	Longwood Research	Huntsville	Alabama
United States	Indiana University Health	Indianapolis	Indiana
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Ocean State Clinical Research Partners	Lincoln	Rhode Island
United States	Robley Rex VAMC	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Vista Health Research	Miami	Florida
United States	Delta Research Partners LLC	Monroe	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions Inc	Orlando	Florida
United States	Health Quest Medical Care	Owensboro	Kentucky
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	Digestive Health Associates of Texas	Richardson	Texas
United States	MedStar Health Research Institute	Rosedale	Maryland
United States	St. Louis Center for Clinical Research	Saint Louis	Missouri
United States	Washington University Medical School	Saint Louis	Missouri
United States	Care Access Research - Salt Lake City	Salt Lake City	Utah
United States	San Antonio Gastroenterology	San Antonio	Texas
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Louisiana Research Center	Shreveport	Louisiana
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Del Sol Research Management, LLC	Tucson	Arizona
United States	Healthcare Research Consultant	Tulsa	Oklahoma
United States	Advanced Gastroenterology	Union City	Tennessee
United States	Ventura Clinical Trials	Ventura	California
United States	Huron Gastroenterology Associates	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Hungary,  Japan,  Netherlands,  Poland,  Romania,  Russian Federation,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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