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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02589665




Registration number
NCT02589665
Ethics application status
Date submitted
27/10/2015
Date registered
28/10/2015
Date last updated
17/06/2020

Titles & IDs
Public title
A Study of Mirikizumab (LY3074828) in Participants With Moderate to Severe Ulcerative Colitis
Scientific title
A Phase 2, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Study of LY3074828 in Subjects With Moderate to Severe Ulcerative Colitis
Secondary ID [1] 0 0
I6T-MC-AMAC
Secondary ID [2] 0 0
15829
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mirikizumab
Treatment: Drugs - Placebo

Experimental: 50 mg Mirikizumab IV Q4W (Induction) - 50 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period. Participants who do not have a clinical response may choose to participate in the unblinded study extension period.

Experimental: 200 mg Mirikizumab IV Q4W (induction) - 200 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period.
Participants who do not have a clinical response may choose to participate in the unblinded study extension period.

Experimental: 600 mg Mirikizumab IV Q4W (Induction) - 600 mg mirikizumab administered every 4 weeks (Q4W) intravenously (IV) during the induction period.
Participants who do not have a clinical response may choose to participate in the unblinded study extension period.

Placebo Comparator: Placebo IV Q4W (Induction) - Placebo administered every 4 weeks (Q4W) intravenously (IV) during the induction period.

Experimental: 200 mg Mirikizumab SC Q4W (Maintenance) - Induction mirikizumab responders were re-randomized: 200 mg mirikizumab administered subcutaneously (SC) Q4W during the maintenance period.

Experimental: 200 mg Mirikizumab SC Q12W (Maintenance) - Induction mirikizumab responders were re-randomized: 200 mg mirikizumab administered subcutaneously (SC) once every 12 weeks (Q12W) during the maintenance period.

Placebo Comparator: Placebo SC Q4W (Maintenance) - Induction placebo responders: Placebo administered subcutaneously (SC) Q4W during the maintenance period.

Experimental: 600mg Mirikizumab IV Q4W Extension Open-Label - Induction non-responders: 600 mg mirikizumab administered intravenously (IV) once every 4 weeks (Q4W) during the Extension Open-Label.

Experimental: 1000mg Mirikizumab IV Q4W Extension Open-Label - Induction non-responders: 1000 mg mirikizumab administered intravenously (IV) once every 4 weeks (Q4W) during the Extension Open-Label.

Experimental: 200mg Mirikizumab SC Q4W Extension Open-Label - Extension Induction responders: 200 mg mirikizumab administered subcutaneously (SC) once every 4 weeks (Q4W) during the Extension Open-Label


Treatment: Drugs: Mirikizumab


Treatment: Drugs: Placebo


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Induction Period: Percentage of Participants With Clinical Remission at Week 12 - Clinical remission at week 12 is a defined as achieving a 9-pt Mayo subscore for rectal bleeding=0, stool frequency=0 or 1 with = 1 point decrease from baseline, and endoscopy=0 or 1, excluding Physician's Global Assessment (PGA).
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 colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration);
Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from 0 (normal) to 3 (severe disease).
The total score ranges from 0 to 9 points, with higher scores representing more severe disease.
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Induction Period: Percentage of Participants With Clinical Response at Week 12 - Clinical response at week 12 is defined as a decrease in the 9-point Mayo subscores (rectal bleeding, stool frequency and the endoscopic findings) inclusive of >= 2 points and >=35% from baseline with either a decrease of rectal bleeding subscore of >=1 or rectal bleeding subscore of 0 or 1.
The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four 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) to 3 (blood only passed);
Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).
The total score ranges from 0 to 9 points, with higher scores representing more severe disease.
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Induction Period: Percentage of Participants With Endoscopic Remission at Week 12 - Endoscopic remission at week 12 is defined as achieving a Mayo endoscopic score of 0 at Week 12. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration);
The total score ranges from 0 to 3 points, with higher scores representing more severe disease.
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Maintenance Period: Percentage of Participants With Endoscopic Remission at Week 52 - Endoscopic remission at week 52 is defined as achieving a Mayo endoscopic subscore of 0 at Week 52. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration);
The total score ranges from 0 to 3 points, with higher scores representing more severe disease.
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Induction Period: Change From Baseline to Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score - The IBDQ is a 32-item subject-completed questionnaire that measures 4 aspects of subjects' lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function (Guyatt et al. 1989). 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 MMRM model for post-baseline measures: Variable = Baseline + Geographical Region + Prior Biologic Therapy Group (N) + Treatment + Time + Treatment*Time (Type III sum of squares).
Timepoint [4] 0 0
Baseline, Week 12
Secondary outcome [5] 0 0
Induction Period: Change From Baseline to Week 12 in 36-Item Short Form Health Survey (SF-36) - SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Domain scores: general health (range: 5-25); physical functioning (range: 10-30); role-physical (range: 4-8); role-emotional (range: 3-15); social functioning (range: 2-10); bodily pain (range: 2-12); vitality (range: 4-20); mental health (range: 5-25). Each raw scale score was converted to a scale score ranging from 0-100 points, with higher values representing a better outcome [(Raw score) - min{raw score}] / (max {raw score} - min{raw score}) x 100]. LS Mean was calculated using Mixed effect Model Repeat Measurement (MMRM) model for post-baseline measures: Variable = Baseline + Geographical Region + Prior Biologic Therapy Group (N) + Treatment + Time + Treatment*Time (Type III sum of squares).
Timepoint [5] 0 0
Baseline, Week 12
Secondary outcome [6] 0 0
Induction Period: Change From Baseline to Week 12 in Patient's Global Impressions of Severity (PGI-S) Score - PGI-S is a 1-item subject-rated questionnaire designed to assess the subject's impression of their disease symptoms at baseline (Guy 1976; Yalcin and Bump 2003). Responses are graded on a 7-point scale in which a score of 1 indicates that the subject's symptom(s) are "normal," a score of 2 indicates that the subject feels "borderline ill," a score of 3 indicates that the subject feels "mildly ill," a score of 4 indicates that the subject(s) feel "moderately ill," and scores of 5, 6, and 7 indicate that the subject feels "markedly ill," "severely ill," and "extremely ill," respectively. LS Mean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Geographical Region + Prior Biologic Therapy Group (N) + Treatment + Time + Treatment*Time (Type III sum of squares).
Timepoint [6] 0 0
Baseline, Week 12
Secondary outcome [7] 0 0
Induction Period: Patient's Global Impressions of Improvement (PGI-I) Score at Week 12 - PGI-I scale is a subject-rated instrument designed to assess the subject's impression of change in their symptom(s) (Guy 1976; Yalcin and Bump 2003). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the subject's symptom(s) is "very much better," a score of 4 indicates that the subject's symptom(s) has experienced "no change," and a score of 7 indicates that the subject's symptom(s) is "very much worse."
Timepoint [7] 0 0
Week 12
Secondary outcome [8] 0 0
Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, Tau) of Mirikizumab - Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, tau) of Mirikizumab
Timepoint [8] 0 0
Induction Period: Day (D) 1, D15 ± 2d, D29 ± 2d, D43 ± 2d, D57 ± 2d, D78-85; Maintenance Period: D85-92,D113± 7d,D141± 7d,D169± 7d,D225 ±7d,D281 ±7d,D337 ±7d,D393± 7d,D448± 7d,D504± 7d,D560± 7d,D616± 7d,D672± 7d,D728± 7d,D784± 7d,D840± 7d
Secondary outcome [9] 0 0
Induction Period: Percentage of Participants With Symptomatic Remission at Week 12 - Symptomatic remission is defined as a stool frequency score of 0 or 1 and a rectal bleeding score of 0.
Stool Frequency Subscore is 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 is based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed).
The total score ranges from 0 to 1 points, with higher scores representing more severe disease.
The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Timepoint [9] 0 0
Week 12
Secondary outcome [10] 0 0
Maintenance Period: Percentage of Participants With Symptomatic Remission at Week 52 - Symptomatic remission is defined as a stool frequency score of 0 or 1 and a rectal bleeding score of 0.
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 colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration);
Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from zero (normal) to 3 (severe disease).
The total score ranges from 0 to 1 points, with higher scores representing more severe disease.
The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Timepoint [10] 0 0
Week 52
Secondary outcome [11] 0 0
Induction Period: Percentage of Participants With Endoscopic Improvement at Week 12 - Endoscopic Improvement defined as achieving an endoscopic findings subscore of 0 or 1. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Timepoint [11] 0 0
Week 12
Secondary outcome [12] 0 0
Maintenance Period: Percentage of Participants With Endoscopic Improvement at Week 52 - Endoscopic Improvement defined as achieving an endoscopic findings subscore of 0 or 1. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Timepoint [12] 0 0
Week 52

Eligibility
Key inclusion criteria
- Have moderate to severe active UC as defined by a Mayo score of 6 to 12 with an
endoscopic subscore =2 within 14 days before the first dose of study treatment (note:
a partial Mayo score of at least 4 and other eligibility criteria must have been met
before endoscopy is performed as a study procedure)

- Have evidence of UC extending proximal to the rectum (=15 centimeters [cm] of involved
colon)

- Up-to-date colorectal cancer surveillance (performed according to local standard), for
subjects with family history of colorectal cancer, personal history of increased
colorectal cancer risk, age >50 years, or other known risk factor

- Participants must either: be naive to biologic therapy (eg, tumor necrosis factor
[TNF] antagonists or vedolizumab) and have at least 1 of the following: inadequate
response or failure to tolerate current treatment with oral or intravenous
corticosteroids or immunomodulators (6-mercaptopurine or azathioprine) or history of
corticosteroid dependence (an inability to successfully taper corticosteroids without
return of UC) OR have received treatment with 1 or more biologic agents (eg, TNF
antagonists or vedolizumab) at doses approved for the treatment of UC with documented
history of failure to respond to or tolerate such treatment
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have been diagnosed with indeterminate colitis, proctitis (distal disease involving
the rectum only; less than 15 cm from the anal verge) or Crohn's Disease

- Have had surgery for treatment of UC or are likely to require surgery for UC during
the study

- Have received any of the following for treatment of UC: cyclosporine or thalidomide
within 30 days of screening, corticosteroid enemas, corticosteroid suppositories, or
topical treatment with 5-aminosalicyclic acid within 30 days of screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Concord
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Fitzroy
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - South Brisbane
Recruitment hospital [4] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Woolloongabba
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
Belgium
State/province [10] 0 0
Ghent
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Canada
State/province [12] 0 0
Calgary
Country [13] 0 0
Canada
State/province [13] 0 0
Montreal
Country [14] 0 0
Canada
State/province [14] 0 0
Montréal
Country [15] 0 0
Czechia
State/province [15] 0 0
Hradec Kralove
Country [16] 0 0
Czechia
State/province [16] 0 0
Hradec Králové
Country [17] 0 0
Czechia
State/province [17] 0 0
Praha 4 Kralove
Country [18] 0 0
Czechia
State/province [18] 0 0
Praha 4
Country [19] 0 0
Czechia
State/province [19] 0 0
Praha
Country [20] 0 0
Denmark
State/province [20] 0 0
Svendborg
Country [21] 0 0
France
State/province [21] 0 0
Clichy
Country [22] 0 0
France
State/province [22] 0 0
Montpellier Cedex 5
Country [23] 0 0
France
State/province [23] 0 0
Nice
Country [24] 0 0
France
State/province [24] 0 0
Saint Priest en Jarez
Country [25] 0 0
France
State/province [25] 0 0
Vandoeuvre Les Nancy
Country [26] 0 0
Georgia
State/province [26] 0 0
Tbilisi
Country [27] 0 0
Hungary
State/province [27] 0 0
Bekescsaba
Country [28] 0 0
Hungary
State/province [28] 0 0
Budapest
Country [29] 0 0
Hungary
State/province [29] 0 0
Szeged
Country [30] 0 0
Hungary
State/province [30] 0 0
Szekszard
Country [31] 0 0
Hungary
State/province [31] 0 0
Vac
Country [32] 0 0
Japan
State/province [32] 0 0
Bunkyo-ku
Country [33] 0 0
Japan
State/province [33] 0 0
Chuo-ku
Country [34] 0 0
Japan
State/province [34] 0 0
Kagoshima-shi
Country [35] 0 0
Japan
State/province [35] 0 0
Kamakura-shi
Country [36] 0 0
Japan
State/province [36] 0 0
Kasugai-shi
Country [37] 0 0
Japan
State/province [37] 0 0
Kawasaki
Country [38] 0 0
Japan
State/province [38] 0 0
Mitaka
Country [39] 0 0
Japan
State/province [39] 0 0
Nishinomiya
Country [40] 0 0
Japan
State/province [40] 0 0
Oita City
Country [41] 0 0
Japan
State/province [41] 0 0
Osaka-City
Country [42] 0 0
Japan
State/province [42] 0 0
Saga-shi
Country [43] 0 0
Japan
State/province [43] 0 0
Sakura
Country [44] 0 0
Japan
State/province [44] 0 0
Shinjuku-ku
Country [45] 0 0
Japan
State/province [45] 0 0
Takasaki
Country [46] 0 0
Japan
State/province [46] 0 0
Toyama
Country [47] 0 0
Japan
State/province [47] 0 0
Toyota-shi
Country [48] 0 0
Japan
State/province [48] 0 0
Tsu-shi
Country [49] 0 0
Japan
State/province [49] 0 0
Yokohama
Country [50] 0 0
Lithuania
State/province [50] 0 0
Kaunas
Country [51] 0 0
Lithuania
State/province [51] 0 0
Vilnius
Country [52] 0 0
Moldova, Republic of
State/province [52] 0 0
Chisinau
Country [53] 0 0
Netherlands
State/province [53] 0 0
Amsterdam
Country [54] 0 0
Poland
State/province [54] 0 0
Bydgoszcz
Country [55] 0 0
Poland
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Elblag
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Poland
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Katowice
Country [57] 0 0
Poland
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Krakow
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Poland
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Lublin
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Poland
State/province [59] 0 0
Rzeszow
Country [60] 0 0
Poland
State/province [60] 0 0
Sopot
Country [61] 0 0
Poland
State/province [61] 0 0
Warszawa
Country [62] 0 0
Poland
State/province [62] 0 0
Wroclaw
Country [63] 0 0
Romania
State/province [63] 0 0
Bucharest
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Oxford
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Winchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main purpose of this study is to test the hypothesis that treatment with mirikizumab is
superior to placebo in providing clinical benefit to participants with moderate to severe
ulcerative colitis (UC). This study will also investigate how the body processes the drug.
Trial website
https://clinicaltrials.gov/show/NCT02589665
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications