An Induction Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03518086
• Collaborator: (none)
• Enrollment: 1,281
• Locations: 532
• Arms: 4
• Anticipated Duration (Months): 54.8
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Mirikizumab in participants with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to, loss of response, or intolerant to conventional or biologic therapy for UC.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Mirikizumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1281 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Induction Study of Mirikizumab in Conventional-Failed and Biologic-Failed Patients With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)
• Actual Study Start Date: Mar 15, 2018
• Actual Primary Completion Date: Jan 21, 2021
• Anticipated Study Completion Date: Oct 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Intravenous (IV) Every 4 Weeks (Q4W) Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	Drug: Placebo; Administered IV
Experimental: 300 Milligram (mg) Mirikizumab IV Q4W 300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	Drug: Mirikizumab; Administered IV; Other Names: LY3074828
Placebo Comparator: Placebo IV Q4W Maximum Extended Enrollment (ME2) Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	Drug: Placebo; Administered IV
Experimental: 300 mg Mirikizumab IV Q4W ME2 300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	Drug: Mirikizumab; Administered IV; Other Names: LY3074828

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clinical Remission at Week 12 [Week 12]

   Clinical remission at week 12 is defined as achieving a modified Mayo score (MMS) subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability), excluding consideration of 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The confidence interval of 99.875% was chosen to match the significance level.

Secondary Outcome Measures

1. Percentage of Participants With Clinical Response at Week 12 [Week 12]

   Clinical response at week 12 is defined as a decrease in the 9-point modified Mayo score (MMS) [rectal bleeding, stool frequency and the endoscopic findings] inclusive of >= 2 points and >=30% from baseline with either a decrease of rectal bleeding subscore of >=1 or rectal bleeding subscore of 0 or 1.The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration).The MMS ranges from 0 to 9 points,with higher scores representing more severe disease. The confidence interval of 99.875% was chosen to match the significance level.

2. Percentage of Participants With Endoscopic Remission at Week 12 [Week 12]

   Endoscopic remission at week 12 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) 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 Mayo endoscopic score ranges from 0 to 3 points, with higher scores representing more severe disease. The confidence interval of 99.875% was chosen to match the significance level.

3. Percentage of Participants With Symptomatic Remission at Week 12 [Week 12]

   Symptomatic remission at week 12 is defined as a Mayo subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline. 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 seen) to 3 (blood alone passed). The confidence interval of 99.875% was chosen to match the significance level.

4. Percentage of Participants With Symptomatic Response at Week 12 [Week 12]

   Symptomatic response at week 12 is defined as ≥30% decrease from baseline in the sum of stool frequency and rectal bleeding 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 seen) to 3 (blood alone passed). The sum of stool frequency and rectal bleeding subscores ranges from 0 to 6.

5. Percentage of Participants With Histologic Remission at Week 12 [Week 12]

   Histologic remission was assessed using the Geboes histologic scoring system developed for assessment of histologic disease activity in ulcerative colitis. Remission was defined as Geboes histological subscore of 0 for grades: 2b (lamina propria neutrophils), and 3 (neutrophils in epithelium), and 4 (crypt destruction), and 5 (erosion or ulceration).

6. Percentage of Participants With Endoscopic Response at Week 12 [Week 12]

   Endoscopic response at week 12 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore. The Mayo endoscopic subscore ranges from 0 to 3 points, with higher scores representing more severe disease.

7. Change From Baseline to Week 12 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS) [Baseline, Week 12]

   The Urgency NRS 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. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes: treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).

8. Change From Baseline to Week 12 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [Baseline, Week 12]

   The IBDQ is a 32-item participant-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. Least square (LS) Mean was calculated using analysis of covariance (ANCOVA) model for post-baseline measures: The ANCOVA model includes: treatment, baseline value, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).

9. Change From Baseline to Week 12 in Fecal Calprotectin [Baseline, Week 12]

   Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes: treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).

10. Pharmacokinetics (PK): Clearance of Mirikizumab [Predose on week 0, week 4, week 8 and post dose on week 0, 4 and 12]

    Clearance of mirikizumab was evaluated. Clearance is estimated based on concentration data collected in the time frame of 0-12 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of UC for at least 3 months prior to baseline.

• Confirmed diagnosis of moderately or severely active UC, as assessed by the modified Mayo score (MMS).

• Demonstrated an inadequate response to, a loss of response to, or an intolerance to conventional or to biologic therapy for UC.

• If female, must meet the contraception requirements.

Exclusion Criteria:

• Participants with a current diagnosis of Crohn's disease or inflammatory bowel disease-unclassified (indeterminate colitis).

• Participants with a previous colectomy.

• Participants with current evidence of toxic megacolon.

• Prior exposure to anti-IL12p40 antibodies (e.g. ustekinumab) or anti-IL-23p19 antibodies (e.g. risankizumab, brazikumab, guselkumab or tildrakizumab).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Digestive Health Specialists of the Southeast	Dothan	Alabama	United States	36305
2	Dcr-Pi, Pc	Litchfield Park	Arizona	United States	85340
3	Maricopa Integrated Health System	Phoenix	Arizona	United States	85008
4	Physicians Research Group	Tempe	Arizona	United States	85284
5	University of Arizona, CATS Research Center	Tucson	Arizona	United States	85724
6	Yuma Gastro LLC	Yuma	Arizona	United States	85364
7	Valley Gastroenterology Cnslts	Arcadia	California	United States	91006
8	Care Access Research	Berkeley	California	United States	94705
9	Citrus Valley Health Partners	Covina	California	United States	91722
10	Valley View Internal Medicine	Garden Grove	California	United States	92843
11	University of California - San Diego	La Jolla	California	United States	92093
12	Om Research, LLC	Lancaster	California	United States	93534
13	Catalina Research Institute, LLC	Montclair	California	United States	91763
14	California Medical Research Group	Northridge	California	United States	91324
15	Gastroenterology Associates	Pasadena	California	United States	91105
16	Clinical Applications Laboratories, Inc.	San Diego	California	United States	92103
17	UCSF Medical Center at Mission Bay	San Francisco	California	United States	94158
18	University of Colorado	Aurora	Colorado	United States	80045
19	Delta Waves Sleep Disorders and Research Center	Colorado Springs	Colorado	United States	80918
20	Gastro Florida	Clearwater	Florida	United States	33756
21	West Central Gastroenterology d/b/a Gastro Florida	Clearwater	Florida	United States	33761
22	Clinical Research of West Florida, Inc. (Clearwater)	Clearwater	Florida	United States	33765
23	Pioneer Clinical Research	Coral Springs	Florida	United States	33067
24	Doral Research Center	Doral	Florida	United States	33166
25	Direct Helpers Medical Center	Hialeah	Florida	United States	33012
26	Wellness Clinical Research	Hialeah	Florida	United States	33012
27	The Center for Gastrointestinal Disorders	Hollywood	Florida	United States	33021
28	Nature Coast Clinical Research, LLC	Inverness	Florida	United States	34452
29	SIH Research, LLC	Kissimmee	Florida	United States	34741
30	Center for Advanced Gastroenterology, PLLC	Maitland	Florida	United States	32751
31	Inpatient Research Clinic, LLC	Miami Lakes	Florida	United States	33014
32	Life Medical Center & Research, Inc	Miami Lakes	Florida	United States	33014
33	Columbus Clinical Services, LLC	Miami	Florida	United States	33125
34	Research Associates of South Florida, LLC	Miami	Florida	United States	33134
35	Coral Research Clinic Corp	Miami	Florida	United States	33186
36	Pharma Research International, Inc.	Naples	Florida	United States	34110
37	Center for Interventional Endoscopy	Orlando	Florida	United States	32804
38	Clintheory Healthcare	Orlando	Florida	United States	32819
39	IMIC, Inc.	Palmetto Bay	Florida	United States	33157
40	Gastroenterology Associates of Pensacola, PA	Pensacola	Florida	United States	32503
41	Florida Digestive Specialist	Saint Petersburg	Florida	United States	33709
42	Florida Medical Clinic LLC	Zephyrhills	Florida	United States	33542-7505
43	Digestive Healthcare of Georgia	Atlanta	Georgia	United States	30309
44	Gastrointestinal Diseases Research	Columbus	Georgia	United States	31904
45	Atlanta Gastroenterology Specialists, PC	Suwanee	Georgia	United States	30024
46	Grand Teton Research Group, PLLC	Idaho Falls	Idaho	United States	83404
47	NorthShore University HealthSystem	Evanston	Illinois	United States	60201
48	Lemah Creek Clinical Research	Oakbrook Terrace	Illinois	United States	60181
49	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
50	Iowa Digestive Disease Center	Clive	Iowa	United States	50325
51	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
52	WestGlen GI Consultants	Shawnee Mission	Kansas	United States	66217
53	Cotton-O'Neil Clinical Research Center, Digestive Health	Topeka	Kansas	United States	66606
54	Texas Digestive Disease Consultants	Baton Rouge	Louisiana	United States	70809
55	Clinical Trials of SWLA, LLC	Lake Charles	Louisiana	United States	70601
56	Delta Research Partners LLC	Monroe	Louisiana	United States	71201
57	Tulane Univ School of Med	New Orleans	Louisiana	United States	70112 2715
58	Nola Research Works, LLC	New Orleans	Louisiana	United States	70125
59	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
60	University of Massachusetts Medical Center	Worcester	Massachusetts	United States	01655
61	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan	United States	48047
62	Henry Ford Health System	Novi	Michigan	United States	48377
63	Gastroenterology Associates of Western Michigan, P.L.C.	Wyoming	Michigan	United States	49519
64	Huron Gastroenterology Associates	Ypsilanti	Michigan	United States	48197
65	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota	United States	55446
66	Washington University Medical School	Saint Louis	Missouri	United States	63110
67	Bozeman Health Deaconess Hospital	Bozeman	Montana	United States	59715
68	Capital Health Medical Center Hopewell	Pennington	New Jersey	United States	08534
69	Holy Name Medical Center	Teaneck	New Jersey	United States	07666
70	Northwell Health	Great Neck	New York	United States	11021
71	NYU Langone Long Island Clinical Research Associates	Lake Success	New York	United States	11042
72	Weill Cornell Medical College	New York	New York	United States	10021
73	Mount Sinai - PRIME	New York	New York	United States	10029
74	University of North Carolina	Chapel Hill	North Carolina	United States	27599
75	Carolina Digestive Diseases	Greenville	North Carolina	United States	27834
76	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157-1045
77	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
78	Trinity Health Center Medical Arts	Minot	North Dakota	United States	58701
79	META Medical Research Institute, LLC	Dayton	Ohio	United States	45432
80	Paramount Medical Research	Middleburg Heights	Ohio	United States	44130
81	Care Access Research - Youngstown	Poland	Ohio	United States	44514
82	Great Lakes Medical Research, LLC	Westlake	Ohio	United States	44145
83	Central Sooner Research	Norman	Oklahoma	United States	73071
84	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
85	Care Access Research LLC	Pottsville	Pennsylvania	United States	17901
86	Digestive Disease Associates, Ltd.	Wyomissing	Pennsylvania	United States	19610
87	Ocean State Clinical Research Partners	Lincoln	Rhode Island	United States	02865
88	Invocare Clinical Research Center	Mauldin	South Carolina	United States	29662
89	Invocare Clinical Research Center	West Columbia	South Carolina	United States	29169
90	Midwest Medical Care	Sioux Falls	South Dakota	United States	57108
91	Gastro One	Germantown	Tennessee	United States	38138
92	Galen Medical Group	Hixson	Tennessee	United States	37343
93	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
94	Doctors Hospital at Renaissance Research Institute	Edinburg	Texas	United States	78539
95	University of Texas Medical Branch at Galveston	Galveston	Texas	United States	77555
96	Digestive Health Associates of Texas	Garland	Texas	United States	75044
97	Houston Methodist Research Ins	Houston	Texas	United States	77030
98	Biopharma Informatic, Inc.	Houston	Texas	United States	77084
99	Gastroenterology Research of San Antonio	San Antonio	Texas	United States	78229
100	Southern Star Research Institute, LLC	San Antonio	Texas	United States	78229
101	BFHC Research	San Antonio	Texas	United States	78249
102	Texas Digestive Disease Consultants	Southlake	Texas	United States	76092
103	GI and Liver Research, LLC	Webster	Texas	United States	77598
104	Care Access Research LLC - Salt Lake City	Ogden	Utah	United States	84403
105	Care Access Research LLC - Salt Lake City	Salt Lake City	Utah	United States	84124
106	Emeritas Research Group	Leesburg	Virginia	United States	20176
107	Blue Ridge Medical Research	Lynchburg	Virginia	United States	24502
108	Gastroenterology Associates, PC	Manassas	Virginia	United States	20110
109	The Gastroenterology Group, P.C.	Reston	Virginia	United States	20191
110	Carilion Clinic	Roanoke	Virginia	United States	24016
111	University of Washington Medical Center	Seattle	Washington	United States	98195-6424
112	Digestive Health Specialists	Tacoma	Washington	United States	98405
113	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin	United States	53215
114	Allegiance Research Specialists, LLC	Milwaukee	Wisconsin	United States	53226
115	Centro de Investigaciones Metabólicas (CINME)	Caba	Buenos Aires	Argentina	C1027AAP
116	Mautalen Salud e Investigacion-Centro de Osteopatías Médicas	Ciudad Autonoma De Buenos Air	Buenos Aires	Argentina	C1128AAF
117	CER Instituto Medico	Quilmes	Buenos Aires	Argentina	B1878DVC
118	Instituto de Investigaciones Clinicas Quilmes	Quilmes	Buenos Aires	Argentina	B1878GEG
119	Fundación de Estudios Clínicos	Rosario	Santa Fe	Argentina	S2000DEJ
120	Sanatorio 9 de Julio SA	San Miguel de Tucuman	Tucuman	Argentina	4000
121	Centro Medico Privado de Reumatologia	SAN M. DE Tucuman	Tucumán	Argentina	T4000AXL
122	Hospital Privado Centro Medico de Cordoba SA	Cordoba		Argentina	X5016KEH
123	John Hunter Hospital	Newcastle	New South Wales	Australia	2305
124	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
125	Coastal Digestive Health	Maroochydore	Queensland	Australia	4558
126	Mater University Hospital	South Brisbane	Queensland	Australia	4101
127	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
128	Box Hill Hospital	Box Hill	Victoria	Australia	3128
129	The Northern Hospital	Epping	Victoria	Australia	3076
130	Melbourne Gastrointestinal Investigation Unit (MGIU)	Malvern	Victoria	Australia	3144
131	The Alfred Hospital	Melbourne	Victoria	Australia	3004
132	The Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
133	Medizinische Universität Innsbruck	Innsbruck		Austria	6020
134	Universitätsklinikum Salzburg	Salzburg		Austria	5020
135	Medical University of Vienna	Vienna		Austria	1090
136	Krankenhaus der Barmherzigen Schwestern	Wien		Austria	1060
137	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen	Belgium	9000
138	AZ Klina	Brasschaat		Belgium	2930
139	AZ Groeninge	Kortrijk		Belgium	8500
140	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven		Belgium	3000
141	Centre Hospitalier de Wallonie picarde - CHwapi A.S.B.L.	Tournai		Belgium	7500
142	Allen Whey Khye Lim Professional Corporation	Edmonton	Alberta	Canada	T5R 1W2
143	The Gordon and Leslie Diamond Health Care Centre	Vancouver	British Columbia	Canada	V5Z 1M9
144	GI Research Institute	Vancouver	British Columbia	Canada	V6Z 2K5
145	PerCuro Clinical Research Ltd.	Victoria	British Columbia	Canada	V8V 3M9
146	Victoria Hospital	London	Ontario	Canada	N6A 4G5
147	University of Western Ontario	London	Ontario	Canada	N6A 5G1
148	Centre de santé et de services sociaux Champlain-Charles-Le Moyne	Greenfield Park	Quebec	Canada	J4V 2H1
149	Hopital Maisonneure-Rosemount	Montreal	Quebec	Canada	H1T 2M4
150	Inflammatory Bowel Disease Centre Montreal General Hospital - MUHC	Montreal	Quebec	Canada	H3G 1A4
151	Anhui Provincial Hospital	Hefei City	Anhui	China	230000
152	The First Affiliated Hospital of Anhui Medical University	HefeiCity	Anhui	China	230022
153	Beijing Friendship Hospital	Beijing	Beijing	China	100050
154	Xiangya Hospital Central South University	Kaifu District	Changsha City	China	410008
155	The Affiliated 2nd Hosp. of Third Military Med. Univ. of PLA	Chongqing	Chongqing	China	400037
156	The First Hospital Affiliated to AMU (Southwest Hospital)	Chongqing	Chongqing	China	400038
157	Fujian Province Hospital	Fuzhou	Fujian	China	350001
158	The Sixth Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510655
159	The University of Hong Kong-Shenzhen Hospital	Shenzhen	Guangdong	China	518053
160	Hainan General Hospital	Haikou	Hainan	China	570311
161	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei	China	430022
162	The Affiliated Drum Tower Hospital of Nanjing University	Nanjing	Jiangsu	China	210008
163	Jiangsu Province Hospital of Chinese Medicine	Nanjing	Jiangsu	China	210029
164	Jiangsu Province Hospital	Nanjing	Jiangsu	China	210029
165	Zhongda Hospital Southeast University	Nanjing	Jiangsu	China	210029
166	Nanjing Medical University - Nanjing Jiangning Hospital	Nanjing	Jiangsu	China	211106
167	Jiangxi Pingxiang People's Hospital	Pingxiang	Jiangxi	China	337055
168	Jilin Central General Hospital	Jilin	Jilin	China	132011
169	The Second Hospital of Dalian Medical University	Dalian	Lianing	China	116000
170	Qilu Hospital of Shandong University	Jinan	Shandong	China	250014
171	Liaocheng People's hospital	Liaocheng	Shandong	China	252000
172	Ruijin Hospital Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200025
173	Renji Hospital Affliated to Shanghai Jiaotong University	Shanghai	Shanghai	China	200127
174	West China Hospital Sichuan University	Chengdu	Sichuan	China	610041
175	No.1 Hospital Affiliated to Xinjiang Medical University	Urumchi	Urumchi	China	830054
176	Kunming Medical College Affiliated First Hospital	Kunming	Yunnan	China	650032
177	The First People's Hospital of Yunnan Province	Kunming	Yunnan	China	650034
178	The Second Affiliated Hospital of Zhejiang University School of Med	Hangzhou	Zhejiang	China	310000
179	First Affiliated Hosp of College of Med, Zhejiang University	Hangzhou	Zhejiang	China	310003
180	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang	China	310016
181	The Second Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325027
182	Tongji Hospital of Tongji University	Wuhan		China	430030
183	University Hospital Center Osijek	Osijek		Croatia	31000
184	CHC Zagreb	Zagreb		Croatia	10000
185	Polyclinic Bonifarm	Zagreb		Croatia	10000
186	Fakultni nemocnice Kralovske Vinohrady	Praha 10	Hl. M. Praha	Czechia	100 34
187	Klinika ResTrial	Praha	Modrany	Czechia	14300
188	Vojenska nemocnice Brno	Brno		Czechia	636 00
189	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia	65691
190	Hepato-gastroenterologie HK, s.r.o.	Hradec Kralove		Czechia	50012
191	Gregar s.r.o.	Olomouc		Czechia	779 00
192	PreventaMed, s.r.o.	Olomouc		Czechia	779 00
193	A-Shine s.r.o.	Plzen		Czechia	31200
194	Mediendo s.r.o.	Praha 8 - Karlin		Czechia	18600
195	ISCARE Clinical Centre	Praha 9		Czechia	19000
196	Sydvestjysk Sygehus Esbjerg	Esbjerg		Denmark	6700
197	Herlev and Gentofte Hospital	Herlev		Denmark	2730
198	Zealand University Hospital Køge	Køge		Denmark	4600
199	Hopital de Hautepierre - Service d'Hépatogastroentérolgie	Strasbourg Cedex	Bas Rhin	France	67098
200	Hopital Saint-Louis	Paris	Cedex 10	France	75475
201	CHU Lille - Hôpital Claude Huriez	Lille cedex	Nord	France	59037
202	Hospices Civils de Lyon - Centre Hospitalier Lyon Sud -	Pierre Benite cedex	Rhone	France	69495
203	CHU Amiens Picardie-Site Sud - RDC Service Hépato gastro	Amiens Cedex	Somme	France	80480
204	CHU Tours - Hôpital Trousseau	Chambray les Tours		France	37170
205	Hopital Beaujon	Clichy		France	92110
206	Hopital Nord de Marseille	Marseille Cedex 20		France	13915
207	Hopital Saint Eloi	Montpellier		France	34295
208	Hopital L'Archet 2	Nice Cedex		France	06200
209	Centre Hospitalier de Pau	Pau CEDEX		France	64000
210	CHU Bordeaux - Hôpital Haut-Lévêque	Pessac Cedex		France	33604
211	CHU de Poitiers- Service d'Hépato-gastro-entérologie,	Poitiers Cedex		France	86021
212	Robert Debre Hospital	Reims		France	51092
213	CHU de Saint Etienne Hopital Nord	Saint Priest en Jarez		France	42270
214	CHRU Nancy Brabois - Hôpital d'Enfants	Vandoeuvre les Nancy		France	54500
215	Staedisches Klinikum Brandenburg	Brandenburg an der Havel	Brandenburg	Germany	14770
216	Medizinische Hochschule Hanover	Hannover	Niedersachsen	Germany	30625
217	Gastro Campus Research GbR	Muenster	Nordrhein Westfalen	Germany	48159
218	Studiengesellschaft BSF Unternehmergesellschaft haftungsbeschraenkt	Halle (Saale),	Sachsen Anhalt	Germany	06108
219	Martin-Luther-Universität Halle-Wittenberg	Halle (Saale)	Sachsen-Anhalt	Germany	06120
220	Charité Universitätsmedizin Berlin Campus Buch	Berlin		Germany	10117
221	Charité Universitätsmedizin Berlin Campus Buch	Berlin		Germany	12203
222	Krankenhaus Waldfriede e. V.	Berlin		Germany	14163
223	Hamburgisches Forschungsinstitut fuer Chronisch Entzuendliche Darmerkrankungen	Hamburg		Germany	20251
224	INLUGA im Haus der Gesundheit	Ludwigshafen		Germany	67067
225	Praxiszentrum Alte Maelzerei	Regensburg		Germany	93053
226	Internistische Praxisgemeinschaft	Weyhe		Germany	28844
227	DRC Gyogyszervizsgalo Rendelointezet Kft	Balatonfüred	EU	Hungary	8230
228	Obudai Egeszsegugyi Centrum Kft	Budapest		Hungary	1036
229	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest		Hungary	1062
230	Semmelweis Egyetem	Budapest		Hungary	1088
231	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
232	Endomedix Diagnosztikai Kozpont	Miskolc		Hungary	3525
233	Karolina Korhaz-Rendelointezet	Mosonmagyarovar		Hungary	9200
234	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont I. Belgyogyaszati Klinika	Szeged		Hungary	6720
235	Clinfan Szolgaltato Kft.	Szekszard		Hungary	7100
236	Javorszky Odon Hospital	Vac		Hungary	2600
237	Osmania Medical College & Hospital	Hyderabad	Andhra Pradesh	India	500012
238	Centre for Liver Research & Diagnostics, Deccan College of Medical Sciences, Owaisi Hospital & Research Centre	Hyderabad	Andhra Pradesh	India	500058
239	Yashoda Hospital	Secunderabad	Andhra Pradesh	India	500003
240	Institute of Digestive and Liver Diseases	Guwahati	Assam	India	781 006
241	Escorts Heart Institute and Research Centre Ltd	New Delhi	Delhi	India	110 025
242	Sir Ganga Ram Hospital	New Delhi	Delhi	India	110060
243	Apollo Research and Innovations, Apollo Hospitals International Ltd	Gandhinagar	Gujarat	India	382428
244	Shree Giriraj Hospital	Rajkot	Gujarat	India	360005
245	Nirmal Hospital Private Limited	Surat	Gujarat	India	395002
246	Bangalore Medical College and Research Institute	Bangalore	Karnataka	India	560 002
247	M S Ramaiah Medical College Hospital	Bangalore	Karnataka	India	560054
248	Lokmanya Hospital	Mumbai	Maharashtra	India	400022
249	Fortis Hospital	Mumbai	Maharashtra	India	400078
250	Poona Medical Foundation. Ruby Hall Clinic	Pune	Maharashtra	India	411 001
251	K E M Hospital and Research Centre	Pune	Maharashtra	India	411011
252	Datta Meghe Institute of Medical Sciences (DU), Acharya Vinoba Bhave Rural Hospital	Wardha	Maharashtra	India	442004
253	Midas Multispecilaity Hopsital Pvt Ltd	Ramdaspeth	Nagpur	India	440010
254	Dayanand Medical College	Ludhiana	Punjab	India	141001
255	S.R. Kalla Hospital	Jaipur	Rajasthan	India	302001
256	King George Medical University	Lucknow	Uttar Pradesh	India	226003
257	Fortis Hospital	Noida	Uttar Pradesh	India	201301
258	SSKM Post Graduate Hospital	Kolkata	West Bengal	India	700020
259	Nil Ratan Sircar Medical College	Kolkata	West Bengal	India	700073
260	Asian Institute of Gastroenterology	Hyderabad		India	500082
261	Gandhi Hospital	Telangana		India	500003
262	Beaumont Hospital	Dublin		Ireland	DUBLIN 9
263	Shaare Zedek Medical Center	Bait Vagan	Jerusalem	Israel	91031
264	Soroka Medical Center - Pediatric Outpatient Clinic	Beer-Sheva		Israel	8410101
265	Meir Medical Center	Kfar Saba		Israel	4428164
266	Galilee Medical Center Department of Internal Medicine A	Nahariya		Israel	2210001
267	Chaim Sheba Medical Center	Ramat Gan		Israel	5262100
268	Kaplan Medical Center	Rehovot		Israel	7610001
269	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
270	Assaf Harofeh Medical Center	Zerifin		Israel	70300
271	Presidio di Rho	Rho	Milano	Italy	20017
272	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
273	Ospedale Sandro Pertini	Roma	RM	Italy	00157
274	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Torre	Roma	Italy	00133
275	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)	Brescia		Italy	25123
276	Azienda ospedaliero-universitaria Mater Domini	Catanzaro		Italy	88100
277	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50134
278	Azienda Ospedaliero Universitaria San Martino	Genova		Italy	16132
279	Gastroenterology and Endoscopy Unit IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation	Milano		Italy	20122
280	Azienda Ospedaliera Universitaria Policlinico de Modena	Modena		Italy	41124
281	Azienda Ospedaliera Universitaria Pisana	Pisa		Italy	56124
282	Policlinico Univ. Agostino Gemelli	Roma		Italy	00168
283	Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona Medicina Interna	Salerno		Italy	84131
284	I.R.C.C.S Policlinico San Donato	San Donato Milanese (MI)		Italy	20097
285	Ospedale Mauriziano Umberto I	Torino		Italy	10128
286	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia Gastroenterologia	Udine		Italy	33100
287	Aichi Medical University Hospital	Nagakute-shi	Aichi-ken	Japan	480-1195
288	Fujita Health University Hospital	Toyoake-shi	Aichi-ken	Japan	470-1192
289	NHO Hirosaki National Hospital	Hirosaki-shi	Aomori-Ken	Japan	036 8545
290	Toho University School of Medicine, Sakura Hospital	Sakura	Chiba	Japan	285-8741
291	Kitakyushu Municipal Medical Center	Kitakyusyu-shi	Fukoka	Japan	802-0077
292	Fukuoka University Chikushi Hospital	Chikushino-shi	Fukuoka-Ken	Japan	818 8502
293	Yukinoseibokai St. Mary's Hospital	Kurume-shi	Fukuoka-Ken	Japan	830 8543
294	Hidaka Coloproctology Clinic	Kurume-shi	Fukuoka-Ken	Japan	839 0809
295	Gunma University Hosptial	Maebashi	Gunma	Japan	371-8511
296	Takasaki General Medical Center	Takasaki	Gunma	Japan	370-0829
297	NHO Mito Medical Center	Ibaraki-machi	HigaShiibaraki-Gun	Japan	311 3193
298	Hiroshima University Hospital	Hiroshima-shi	Hiroshima-ken	Japan	734-8551
299	Asahikawa City Hospital	Asahikawa	Hokkaido	Japan	070-8610
300	Tokushukai Sapporo Tokushukai Hospital	Sapporo-shi	Hokkaido	Japan	004 0041
301	Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital	Sapporo-shi	Hokkaido	Japan	060 0033
302	Tokushukai Sapporo Higashi Tokushukai Hospital	Sapporo-shi	Hokkaido	Japan	065 0033
303	Aoyama Clinic GI Endoscopy & IBD Center	Kobe-shi	Hyogo-Ken	Japan	650 0015
304	Takamatsu Red Cross Hospital	Takamatsu	Kagawa	Japan	760-0017
305	Kagawa Prefectural Central Hospital	Takamatsu	Kagawa	Japan	760-8557
306	Sameshima Hospital	Kagoshima-shi	Kagoshima	Japan	892-0846
307	Kitasato University Hospital	Sagamihara-shi	Kanagawa-ken	Japan	252-0375
308	Sankikai Yokohama Shin midori General Hospital	Yokohama-shi	Kanagawa-Ken	Japan	226 0025
309	Gokeikai Ofuna Chuo Hospital	Kamakura-shi	Kanagawa	Japan	247-0056
310	Kawasaki Municipal Kawasaki Hospital	Kawasaki	Kanagawa	Japan	210-0013
311	Showa University Northern Yokohama Hospital	Yokohama	Kanagawa	Japan	224-8503
312	Yokohama City University Medical Center	Yokohama	Kanagawa	Japan	232-0024
313	Kumamoto University Hospital	Kumamoto-shi	Kumamoto	Japan	860-0012
314	NHO Kyoto Medical Center	Kyoto-shi	Kyoto	Japan	612 8555
315	Mie University Hospital	Tsu	Mie	Japan	514-8507
316	Takagi Clinic	Sendai-shi	Miyagi-Ken	Japan	981 3213
317	Nagaoka Chuo General Hospital	Nagaoka-shi	Niigata	Japan	940-8653
318	Ishida Clinic of IBD and Gastroenterology	Oita-shi	Oita-Ken	Japan	870 0823
319	Shinseikai Sai Gastroenterology, proctology	Fujiidera-shi	Osaka Fu	Japan	583 0027
320	Kinshukai Infusion Clinic	Osaka-City	Osaka-fu	Japan	530-0011
321	NHO Osaka National Hospital	Osaka-shi	Osaka	Japan	540 0006
322	Osaka University Hospital	Suita-shi	Osaka	Japan	565 0871
323	Saga-Ken Medical Center Koseikan	Saga-Shi	Saga-Ken	Japan	840-8571
324	Kumagaya General Hospital	Kumagaya-shi	Saitama-Ken	Japan	360-8567
325	Tokitokai Tokito Clinic	Saitama-shi	Saitama-Ken	Japan	336 0963
326	Matsuaikai Matsuda Hospital	Hamamatsu-shi	Shizuoka-Ken	Japan	4328061
327	Jichi Medical University Hospital	Shimotsuke-shi	Tochigi-Ken	Japan	329-0498
328	Mitsui Memorial Hospital	Chiyoda-ku	Tokyo-To	Japan	101-8643
329	Center Hospital of the National Center for Global Health and Medicine	Shinjuku-ku	Tokyo-To	Japan	162 8655
330	Juntendo University Hospital	Bunkyo-ku	Tokyo	Japan	113-8431
331	Tokyo Medical And Dental University Medical Hospital	Bunkyō	Tokyo	Japan	113-8519
332	Showa University Koto Toyosu Hospital	Koto-ku	Tokyo	Japan	135 8577
333	Kitasato University Kitasato Institute Hospital	Minato-Ku	Tokyo	Japan	108 8642
334	Kyorin University Hospital	Mitaka	Tokyo	Japan	181-8611
335	JHCO Tokyo Yamate Medical Center	Shinjuku-ku	Tokyo	Japan	169-0073
336	Toyama Prefectural Central Hospital	Toyama-Shi	Toyama	Japan	930-8550
337	Fukuoka University Hospital	Fukuoka		Japan	814-0180
338	Okayama University Hospital	Okayama		Japan	700-8558
339	The Catholic University of Daejeon St. Mary's Hospital	Jung-gu	Daejeon	Korea, Republic of	34943
340	Severance Hospital	Wonju-si	Gangwon-do	Korea, Republic of	26426
341	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do	Korea, Republic of	15355
342	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16247
343	Ajou University Hospital	Suwon	Gyeonggi-do	Korea, Republic of	16499
344	Hanyang University Guri Hospital	Guri-si	Gyeonggido	Korea, Republic of	11923
345	Kyung Hee University Hospital	Seoul	Korea	Korea, Republic of	02447
346	Asan Medical Center	Seoul	Korea	Korea, Republic of	05505
347	Dong-A University Hospital	Busan	Pusan-Kwangyǒkshi	Korea, Republic of	49201
348	Kangbuk Samsung Hospital	Seoul	Seoul-teukbyeolsi [Seoul]	Korea, Republic of	03181
349	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]	Korea, Republic of	06351
350	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
351	Kyungpook National University Medical Center Chilgok Hospital	Daegu		Korea, Republic of	41404
352	Yeungnam Univeristy Medical Center	Daegu		Korea, Republic of	42415
353	Seoul National University Hospital	Seoul		Korea, Republic of	03080
354	Ewha Womans University Mokdong Hospital	Seoul		Korea, Republic of	07985
355	Digestive Diseases Center "Gastro"	Riga		Latvia	1079
356	Pauls Stradins Kliniska Universitates Slimnica	Riga		Latvia	LV-1002
357	Riga Eastern Clinical University Hospital	Riga		Latvia	LV-1038
358	Hospital of Lithuanian University of Health Sciences Kaunas	Kaunas		Lithuania	50161
359	Republic Hospital of Klaipeda	Klaipeda		Lithuania	92231
360	Klaipeda Seamen's Hospital	Klaipeda		Lithuania	92288
361	Respublikine Panevezio Ligonine	Panevezys		Lithuania	LT-35144
362	Vilnius University Hospital Santariskiu Clinics	Vilnius		Lithuania	LT-08661
363	Hospital Sultanah Bahiyah	Alor Star	Kedah	Malaysia	05460
364	Pusat Penyelidikan Klinikal (CRC), Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan	Malaysia	15586
365	Universiti Sains Malaysia	Kubang Kerian	Kelantan	Malaysia	16150
366	University Malaya Medical Centre	Lembah Pantai	Kuala Lumpur	Malaysia	59100
367	Hospital Pulau Pinang	Georgetown	Penang	Malaysia	10450
368	Hospital Ampang	Ampang	Selangor	Malaysia	68000
369	Pusat Perubatan University Kebangsaan Malaysia	Cheras, Kuala Lumpur		Malaysia	56000
370	Clinicos Asociados BOCM, S.C.	Mexico	DF	Mexico	03300
371	Centro de Investigación Clínica Acelerada	Mexico City	Distrito Federal	Mexico	07020
372	Clinical Research Institute S C	Tlalnepantla	Edo De Mex	Mexico	54055
373	Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.	Zapopan	Jalisco	Mexico	45030
374	Christus Muguerza Sur S.A. de C.V.	Monterrey	Nuevo León	Mexico	64908
375	Centro Para el Desarrollo de la Medicina y de Asistencia Med	Culiacan	Sinaloa	Mexico	80230
376	Clinical Medical Research S.C.	Orizaba	Veracruz	Mexico	94300
377	Scientia Investigacion Clinica S.C.	Chihuahua		Mexico	31203
378	Sociedad de Metabolismo y Corazon S.C.	Veracruz		Mexico	91900
379	St Elisabeth Ziekenhuis	Tilburg	Noord Brabant	Netherlands	5022 GC
380	Academisch Medisch Centrum	Amsterdam	Noord-Holland	Netherlands	1105 AZ
381	Amphia Ziekenhuis	Breda		Netherlands	4818 CK
382	Albert Schweitzer Ziekenhuis	Dordrecht		Netherlands	3318 AT
383	Bernhoven Ziekenhuis	Uden		Netherlands	5406 PT
384	UMC Utrecht, Dept. of Internal Medicine, MDL	Utrecht		Netherlands	3584 CX
385	Szpital Uniwersytecki Nr 2 w Bydgoszczy, Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej	Bydgoszcz	Kujawsko-pomorskie	Poland	85-168
386	Promedica S.C	Bedzin		Poland	42-500
387	Centrum Medyczne Pratia Bydgoszcz	Bydgoszcz		Poland	85-796
388	NZOZ ALL-MEDICUS, Zaklad Gastroenterologii	Katowice		Poland	40-660
389	Indywidualna Specjalistyczna Praktyka Lekarska	Knurow		Poland	44-190
390	Topolowa Medicenter	Krakow		Poland	31-506
391	GASTROMED Zakład Opieki Zdrowotnej	Lublin		Poland	20-582
392	Samodzielny Publiczny Szpital Kliniczny nr 4	Lublin		Poland	20-954
393	Medicenter Nowy Targ	Nowy Targ		Poland	34-400
394	Wojewodzki Specjalistyczny Szpital w Olsztynie	Olsztyn		Poland	10-561
395	Endoskopia sp z o. o	Sopot		Poland	81-756
396	KO-MED Centra Kliniczne Staszow	Staszow		Poland	28-200
397	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin		Poland	71-434
398	Niepubliczny Zaklad Opieki Zdrowotnej SONOMED	Szczecin		Poland	71-685
399	Gastromed Kopoń Zmudziński I Wspólnicy Spółka Jawna Specjalistyczne Centrum Gastrologii I Endoskopii	Torun		Poland	87-100
400	Nzoz Formed	Wadowice		Poland	34-100
401	Warsaw IBD Point Profesor Kierkus	Warszawa		Poland	00-728
402	Centrum Zdrowia Matki, Dziecka i Młodzieży (CZMDM) Przychodnie	Warszawa		Poland	00635
403	Centrum Medyczne NeuroProtect	Warszawa		Poland	01-697
404	Centralny Szpital Kliniczny MSWiA	Warszawa		Poland	02-507
405	Vivamed	Warszawa		Poland	03-580
406	PlanetMed Sp.z o.o.	Wroclaw		Poland	52-210
407	LexMedica Osrodek Badan Klinicznych	Wroclaw		Poland	53 114
408	ETG Zamosc	Zamosc		Poland	22-400
409	CCBR Clinical Research	Bucharest	București	Romania	030463
410	MedLife Grivita	Bucuresti		Romania	010719
411	Spitalul Clinic Colentina	Bucuresti		Romania	020125
412	Institutul Clinic Fundeni	Bucuresti		Romania	022328
413	Institutul Clinic Fundeni	Bucuresti		Romania	022328
414	Hifu Terramed Conformal SRL	Bucuresti		Romania	031864
415	Centrul Medical Unirea SRL	Bucuresti		Romania	040055
416	Spital Pelican Oradea	Oradea		Romania	410469
417	Multidisciplinary Medical Clinic "Anthurium"	Barnaul		Russian Federation	656043
418	Medical and Sanitary Division of Severstal	Cherepovets		Russian Federation	162600
419	LLC MA New Hospital	Ekaterinburg		Russian Federation	620109
420	Irkutsk State Medical Academy of Continuing Education	Irkutsk		Russian Federation	664049
421	LLC Alliance Biomedical - Ural Group	Izhevsk		Russian Federation	426061
422	Clinical Trials Center of Medical Institute	Kaliningrad		Russian Federation	236035
423	State Autonomous Institution of Healthcare "Republican Clinical Hospital of the Ministry of Healthcare of Republic Tatarstan"	Kazan		Russian Federation	420064
424	SIH Kemerovo Regional Clinical Hosptial	Kemerovo		Russian Federation	650066
425	SBHI Regional Clinical Hospital #2 MoH of Krasnodar region	Krasnodar		Russian Federation	350000
426	Medical rehabilitation center	Moscow		Russian Federation	125367
427	Moscow Budgetary State Healthcare Institution City Clinical Hospital 24	Moscow		Russian Federation	127015
428	Nizhegorodskiy Regional Clinical Hospital N.A.Semashko	Nizhniy Novgorod		Russian Federation	603126
429	Private Healthcare Institution Clinical Hospital Russian Railways - Medicine of Nizhniy Novgorod	Nizhniy Novgorod		Russian Federation	603140
430	LLC "Medicine Center SibNovoMed"	Novosibirsk		Russian Federation	630005
431	LLC Novosibirsk GastroCenter	Novosibirsk		Russian Federation	630007
432	Clinical Diagnostic Center Ultramed	Omsk		Russian Federation	644024
433	Karelia Republican Hospital V.A. Baranova	Petrozavodsk		Russian Federation	185019
434	Rostov State Medical University	Rostov-on-Don		Russian Federation	344022
435	Saint Petersburg State Medical University n.a. Pavlov I.P.	Saint Petersburg		Russian Federation	197022
436	Pokrovskaya Municipal Hospital	Saint-Petersburg		Russian Federation	195067
437	Non-state Healthcare Institution "Roadway Clinical Hospital of OJSC Russian Railways"	Saint-Petersburg		Russian Federation	195271
438	LLC Gastroenterology Centre Expert	Saint-Petersburg		Russian Federation	197110
439	SBIH City Clinical Hospital #31	Saint-Petersburg		Russian Federation	197110
440	Medical Institute REAVIZ	Samara		Russian Federation	443001
441	City Mariinskaya Hospital	St. Petersburg		Russian Federation	191104
442	Saint-Petersburg City Hospital of Saint Elizabeth	St. Petersburg		Russian Federation	195257
443	LLC Scientific Research Centre EKO-Bezopasnost	St. Petersburg		Russian Federation	196143
444	OOO "OrKli"	St. Petersburg		Russian Federation	199147
445	Stavropol State Medical Academy	Stavropol		Russian Federation	355018
446	SBI of Healthcare of Leningrad region "Clinical Interregional Hospital of Tosno"	Tosno		Russian Federation	187000
447	Yaroslavl Municipal HI Clinical Hospital #8	Yaroslavl		Russian Federation	150030
448	King Fahad Specialist Hospital-Dammam	Dammam		Saudi Arabia	15215
449	King Faisal Specialist Hospital & Research Center	Riyadh		Saudi Arabia	12713
450	Clinical Center Bezanijska Kosa	Belgrade	NAP	Serbia	11080
451	Clinical Center Zvezdara	Belgrade		Serbia	11000
452	Clinical Center Kragujevac Gastroenterohepatology Clinic	Kragujevac		Serbia	34000
453	Clinical Hospital Center Kragujevac	Kragujevac		Serbia	34000
454	General Hospital Dr Radivoj Simonovic	Sombor		Serbia	25000
455	General Hospital Sremska Mitrovica	Sremska Mitrovica		Serbia	22000
456	General Hospital Uzice	Uzice		Serbia	31000
457	Clinical Center Zemun	Zemun		Serbia	11080
458	General Hospital "Djordje Joanovic"	Zrenjanin		Serbia	23000
459	Fakultna nemocnica s poliklinikou Roosevelta Banska Bystrica	Banska Bystrica		Slovakia	975 17
460	Alian, s.r.o.	Bardejov		Slovakia	08501
461	Univerzitna nemocnica Bratislava-Nemocnica Stare Mesteo	Bratislava		Slovakia	813 69
462	Univerzitna nemocnica Bratislava	Bratislava		Slovakia	82007
463	KM Management spol. s r.o. Gastroenterologicke a hepatologicke centrum	Nitra		Slovakia	94901
464	Gastro I s.r.o., Gastroenterologická ambulancia	Prešov		Slovakia	08001
465	Endomed, s.r.o.- Gastroenterologicka ambulancia	Vranov N. Toplou		Slovakia	09301
466	Hospital Universitario Virgen Del Rocio	Sevilla	Andalucía	Spain	41013
467	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain	33011
468	Hospital Universitari Son Espases	Palma de Mallorca	Baleares Islands	Spain	07120
469	Hospital Universitario Marques De Valdecilla	Santander	Cantabria	Spain	39008
470	Hospital De Fuenlabrada	Fuenlabrada	Madrid	Spain	28942
471	Complejo Hospitalario De Navarra	Pamplona	Navarra	Spain	31008
472	Hospital de Sagunto	Port De Sagunto	Valencia	Spain	46520
473	Instituto de Ciencias Médicas	Alicante		Spain	03004
474	Hospital San Pedro de Alcantara	Caceres		Spain	10003
475	Hospital Universitario Reina Sofia Comite Etico	Cordoba		Spain	14004
476	Hospital Universitari de Girona	Girona		Spain	17007
477	Hospital General Juan Ramón Jiménez	Huelva		Spain	21005
478	Complexo Hospitalario Universitario A Coruña, CHUAC	La Coruña		Spain	15006
479	Hospital De Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria		Spain	35010
480	Hospital Universitario La Paz	Madrid		Spain	28046
481	Hospital Rio Hortega	Valladolid		Spain	47012
482	Inselspital Bern	Bern		Switzerland	3010
483	Praxis Balsiger, Seibold & Partner und Crohn-Colitis-Zentrum	Bern		Switzerland	3012
484	Kantonsspital St.Gallen	St.Gallen		Switzerland	9007
485	Universitätsspital Zürich USZ Zürich	Zürich		Switzerland	8091
486	Changhua Christian Hospital	Changhua		Taiwan	500
487	China Medical University Hospital	Taichung City		Taiwan	40447
488	Health management center	Taipei		Taiwan	10002
489	Gazi University Faculty of Medicine	Besevler	Ankara	Turkey	65600
490	Hacettepe University Faculty of Medicine	Sihhiye	Ankara	Turkey	6100
491	Antalya Training and Research Hospital	Muratpasa	Antayla	Turkey	7100
492	Istanbul University Cerrahpasa Medical Faculty	Istanbul	Faith	Turkey	34096
493	Acibadem Universitesi - Acibadem Kozyatagi Hastanesi	Kadıkoy	Istanbul	Turkey	34734
494	Kocaeli University Medical Faculty Hospital	Izmit	Kocaeli	Turkey	41380
495	Mersin University Medical Faculty	Yenişehir	Mersin	Turkey	33110
496	Gaziantep University Medical Faculty	Gaziantep		Turkey	27310
497	Acibadem Fulya Hospital	Istanbuk		Turkey	34349
498	Ege University Medicine of Faculty	Izmir		Turkey	35100
499	Dokuz Eylul University Hospital	Izmir		Turkey	35340
500	Ivano-Frankivsk Regional Clinical Hospital	Ivano-Frankivsk	Ivano-Frankivsk Region	Ukraine	76008
501	Medical Center of Limited Liability Company Medical Center Clinic of Family Medicine	Dnipro		Ukraine	49038
502	Kharkiv City Student Hospital	Kharkiv		Ukraine	61002
503	CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2	Kharkiv		Ukraine	61037
504	GI L.T. Malaya TI Namsu	Kharkiv		Ukraine	61039
505	CI Kherson CCH	Kherson		Ukraine	73000
506	Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus	Kropyvnytskyi		Ukraine	25006
507	Kyiv Municipal Clinical Hospital #1	Kyiv		Ukraine	02091
508	Medical Centre CONSILIUM MEDICAL	Kyiv		Ukraine	04050
509	Communal institution of the Kyiv Regional Council "Kyiv Regional Clinical Oncology Dispensary"	Kyiv		Ukraine	04078
510	Communal institution of the Kyiv Regional Council "Kyiv Regional Clinical Oncology Dispensary"	Kyiv		Ukraine	04107
511	Communal Non-Commercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital	Liviv		Ukraine	79010
512	Lviv Clinical Hospital at Railway Transport of Division Healthcare Center PJSC Ukrainian Railway Sta	Lviv		Ukraine	79007
513	Communal City Clinical Hospital of Ambulance	Lviv		Ukraine	79015
514	Communal Enterprise "Odesa Regional Clinical Hospital"	Odesa		Ukraine	65000
515	Communal Institution "Poltava Reg.Cl.H. n.a.M.V.Sklifosovskogo"	Poltava		Ukraine	36011
516	A. Novak Transcarpathian Regional Clinical Hospital	Uzhgorod		Ukraine	88000
517	Vinnytsia RCH of Veterans of War Dept of Therapy#1 Vinnytsia M.I.Pyrogov NMU	Vinnytsia		Ukraine	21005
518	MCIC MC LLC Health Clinic	Vinnytsia		Ukraine	21009
519	CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM	Vinnytsia		Ukraine	21029
520	Private Small Enterprise, Medical Center Pulse	Vinnytsia		Ukraine	21029
521	M.I. Pyrogov Regional Clinical Hospital	Vinnytsya		Ukraine	21018
522	Diaservis Ltd	Zaporizhzhia		Ukraine	69035
523	Communal Institution of Kyiv Regional Council Kyiv Regional Hospital #2	Zaporizhzhia		Ukraine	69104
524	Queens Hospital	Romford	Essex	United Kingdom	RM7 0AG
525	Royal Hampshire County Hospital	Winchester	Hants	United Kingdom	SO22 5DG
526	Fairfield General Hospital	Bury	Lancashire	United Kingdom	BL9 7TD
527	St Thomas' Hospital	Great Maze Pond	London	United Kingdom	SE1 9RT
528	Ninewells Hospital	Dundee	Scotland	United Kingdom	DD1 9SY
529	Whipps Cross University Hospital	London	Surrey	United Kingdom	E11 1NR
530	St James's University Hospital	Leeds	Vinnytsia	United Kingdom	LS9 7TF
531	Morriston Hospital	Swansea	Wales	United Kingdom	SA6 6NL
532	Queen Elizabeth University Hospital	Glasgow		United Kingdom	G51 4TF

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol: AMAN 05 Protocol (a)_Redacted - Sep 12, 2019
• Study Protocol: AMAN 05 ME2 Protocol Addenda (5)_Redacted - Mar 19, 2018
• Statistical Analysis Plan - Jan 14, 2021

More Information

Additional Information:

• An Induction Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03518086
• Other Study ID Numbers: 16591; I6T-MC-AMAN; 2017-003229-14
• First Posted: May 8, 2018
• Last Update Posted: Feb 28, 2022
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: Interleukin-23 (IL-23) antibody; IL-23p19
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Mirikizumab

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 3:1 ratio to 300 milligram (mg) mirikizumab intravenously (IV) every 4 weeks (Q4W) or placebo IV Q4W. Results for maximum extended enrollment (ME2) participants will be posted after the study completion.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W	Placebo IV Q4W ME2 Cohort	300 mg Mirikizumab IV Q4W ME2 Cohort
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Period Title: Overall Study
STARTED	322	959	0	0
Received at Least One Dose of Study Drug	321	958	0	0
COMPLETED	285	920	0	0
NOT COMPLETED	37	39	0	0

Baseline Characteristics

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W	Total
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	Total of all reporting groups
Overall Participants	322	959	1281
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (13.78)	42.8 (13.83)	42.4 (13.83)
Sex: Female, Male (Count of Participants)
Female	140 43.5%	367 38.3%	507 39.6%
Male	182 56.5%	592 61.7%	774 60.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 2.8%	22 2.3%	31 2.4%
Not Hispanic or Latino	27 8.4%	92 9.6%	119 9.3%
Unknown or Not Reported	286 88.8%	845 88.1%	1131 88.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.6%	10 1%	12 0.9%
Asian	68 21.1%	224 23.4%	292 22.8%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.1%	1 0.1%
Black or African American	2 0.6%	10 1%	12 0.9%
White	247 76.7%	704 73.4%	951 74.2%
More than one race	2 0.6%	1 0.1%	3 0.2%
Unknown or Not Reported	1 0.3%	9 0.9%	10 0.8%
Region of Enrollment (Count of Participants)
Argentina	3 0.9%	8 0.8%	11 0.9%
Australia	4 1.2%	10 1%	14 1.1%
Austria	2 0.6%	6 0.6%	8 0.6%
Belgium	3 0.9%	6 0.6%	9 0.7%
Canada	11 3.4%	23 2.4%	34 2.7%
China	2 0.6%	16 1.7%	18 1.4%
Croatia	1 0.3%	1 0.1%	2 0.2%
Czechia	20 6.2%	35 3.6%	55 4.3%
Denmark	0 0%	7 0.7%	7 0.5%
France	15 4.7%	49 5.1%	64 5%
Germany	6 1.9%	33 3.4%	39 3%
Hungary	7 2.2%	16 1.7%	23 1.8%
India	21 6.5%	62 6.5%	83 6.5%
Ireland	0 0%	1 0.1%	1 0.1%
Israel	3 0.9%	14 1.5%	17 1.3%
Italy	12 3.7%	25 2.6%	37 2.9%
Japan	35 10.9%	102 10.6%	137 10.7%
Latvia	6 1.9%	24 2.5%	30 2.3%
Lithuania	6 1.9%	16 1.7%	22 1.7%
Malaysia	0 0%	6 0.6%	6 0.5%
Mexico	2 0.6%	10 1%	12 0.9%
Netherlands	2 0.6%	9 0.9%	11 0.9%
Poland	32 9.9%	104 10.8%	136 10.6%
Romania	2 0.6%	13 1.4%	15 1.2%
Russia	28 8.7%	79 8.2%	107 8.4%
Serbia	8 2.5%	13 1.4%	21 1.6%
Slovakia	3 0.9%	21 2.2%	24 1.9%
South Korea	5 1.6%	23 2.4%	28 2.2%
Spain	7 2.2%	15 1.6%	22 1.7%
Switzerland	2 0.6%	9 0.9%	11 0.9%
Taiwan	0 0%	3 0.3%	3 0.2%
Turkey	5 1.6%	6 0.6%	11 0.9%
Ukraine	26 8.1%	68 7.1%	94 7.3%
United Kingdom	7 2.2%	11 1.1%	18 1.4%
United States	36 11.2%	115 12%	151 11.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clinical Remission at Week 12
Description	Clinical remission at week 12 is defined as achieving a modified Mayo score (MMS) subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability), excluding consideration of 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The confidence interval of 99.875% was chosen to match the significance level.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (99.88% Confidence Interval) [percentage of participants]	13.3 4.1%	24.2 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.00006
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 99.875%; 3.2 to 19.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Clinical Response at Week 12
Description	Clinical response at week 12 is defined as a decrease in the 9-point modified Mayo score (MMS) [rectal bleeding, stool frequency and the endoscopic findings] inclusive of >= 2 points and >=30% from baseline with either a decrease of rectal bleeding subscore of >=1 or rectal bleeding subscore of 0 or 1.The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration).The MMS ranges from 0 to 9 points,with higher scores representing more severe disease. The confidence interval of 99.875% was chosen to match the significance level.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (99.88% Confidence Interval) [percentage of participants]	42.2 13.1%	63.5 6.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	21.4
	Confidence Interval	(2-Sided) 99.875%; 10.8 to 32.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Endoscopic Remission at Week 12
Description	Endoscopic remission at week 12 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) 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 Mayo endoscopic score ranges from 0 to 3 points, with higher scores representing more severe disease. The confidence interval of 99.875% was chosen to match the significance level.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (99.88% Confidence Interval) [percentage of participants]	21.1 6.6%	36.3 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.4
	Confidence Interval	(2-Sided) 99.875%; 6.3 to 24.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Symptomatic Remission at Week 12
Description	Symptomatic remission at week 12 is defined as a Mayo subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline. 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 seen) to 3 (blood alone passed). The confidence interval of 99.875% was chosen to match the significance level.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (99.88% Confidence Interval) [percentage of participants]	27.9 8.7%	45.5 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.5
	Confidence Interval	(2-Sided) 99.875%; 11.4 to 23.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With Symptomatic Response at Week 12
Description	Symptomatic response at week 12 is defined as ≥30% decrease from baseline in the sum of stool frequency and rectal bleeding 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 seen) to 3 (blood alone passed). The sum of stool frequency and rectal bleeding subscores ranges from 0 to 6.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (95% Confidence Interval) [percentage of participants]	52.4 16.3%	72.0 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	20.2
	Confidence Interval	(2-Sided) 95%; 13.8 to 26.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Histologic Remission at Week 12
Description	Histologic remission was assessed using the Geboes histologic scoring system developed for assessment of histologic disease activity in ulcerative colitis. Remission was defined as Geboes histological subscore of 0 for grades: 2b (lamina propria neutrophils), and 3 (neutrophils in epithelium), and 4 (crypt destruction), and 5 (erosion or ulceration).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (95% Confidence Interval) [percentage of participants]	15.6 4.8%	29.3 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	13.7
	Confidence Interval	(2-Sided) 95%; 8.6 to 18.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Endoscopic Response at Week 12
Description	Endoscopic response at week 12 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore. The Mayo endoscopic subscore ranges from 0 to 3 points, with higher scores representing more severe disease.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Number (95% Confidence Interval) [percentage of participants]	36.1 11.2%	55.4 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	19.5
	Confidence Interval	(2-Sided) 95%; 13.2 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline to Week 12 in Bowel Urgency Based on the Urgency Numeric Rating Scale (NRS)
Description	The Urgency NRS 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. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes: treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline urgency NRS measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Least Squares Mean (Standard Error) [score on a scale]	-1.63 (0.141)	-2.59 (0.083)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 99.875%; -1.47 to -0.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.159
	Estimation Comments	The confidence interval of 99.875 % was chosen to match the significance level.

9. Secondary Outcome

Title	Change From Baseline to Week 12 in Health Related Quality of Life: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
Description	The IBDQ is a 32-item participant-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. Least square (LS) Mean was calculated using analysis of covariance (ANCOVA) model for post-baseline measures: The ANCOVA model includes: treatment, baseline value, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline IBDQ measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	294	868
Least Squares Mean (Standard Error) [score on a scale]	25.21 (1.798)	38.42 (1.108)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	13.21
	Confidence Interval	(2-Sided) 95%; 9.28 to 17.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.005
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline to Week 12 in Fecal Calprotectin
Description	Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes: treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4-6] or [7-9]), and region (North America/Europe/Other).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intention-to-treat population (mITT): All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline fecal calprotectin measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Arm/Group Title	Placebo IV Q4W	300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	206	665
Least Squares Mean (Standard Error) [milligram per kilogram (mg/kg)]	-939.69 (196.557)	-1875.29 (116.138)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, 300 mg Mirikizumab IV Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-935.60
	Confidence Interval	(2-Sided) 95%; -1363.64 to -507.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 218.090
	Estimation Comments

11. Secondary Outcome

Title	Pharmacokinetics (PK): Clearance of Mirikizumab
Description	Clearance of mirikizumab was evaluated. Clearance is estimated based on concentration data collected in the time frame of 0-12 weeks.
Time Frame	Predose on week 0, week 4, week 8 and post dose on week 0, 4 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	300 mg Mirikizumab IV Q4W
Arm/Group Description	300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
Measure Participants	952
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour (L/h)]	0.0224 (38)

Adverse Events

Time Frame	Up To 12 Weeks
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	Placebo IV Q4W		300 mg Mirikizumab IV Q4W
Arm/Group Description	Placebo given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.		300 mg mirikizumab given as an IV infusion Q4W on Weeks 0, 4, 8 for 12 weeks.
All Cause Mortality
	Placebo IV Q4W		300 mg Mirikizumab IV Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/321 (0%)		0/958 (0%)
Serious Adverse Events
	Placebo IV Q4W		300 mg Mirikizumab IV Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/321 (5.3%)		27/958 (2.8%)
Blood and lymphatic system disorders
Anaemia	1/321 (0.3%)	1	1/958 (0.1%)	1
Cardiac disorders
Acute myocardial infarction	1/321 (0.3%)	1	0/958 (0%)	0
Ear and labyrinth disorders
Vertigo	0/321 (0%)	0	1/958 (0.1%)	1
Gastrointestinal disorders
Colitis ulcerative	10/321 (3.1%)	10	8/958 (0.8%)	8
Lower gastrointestinal haemorrhage	0/321 (0%)	0	1/958 (0.1%)	1
Infections and infestations
Acute sinusitis	1/321 (0.3%)	1	0/958 (0%)	0
Cytomegalovirus colitis	0/321 (0%)	0	1/958 (0.1%)	1
Gastroenteritis viral	0/321 (0%)	0	1/958 (0.1%)	1
Intestinal sepsis	0/321 (0%)	0	1/958 (0.1%)	1
Klebsiella infection	0/321 (0%)	0	1/958 (0.1%)	1
Pneumonia	0/321 (0%)	0	2/958 (0.2%)	2
Sinusitis	1/321 (0.3%)	1	0/958 (0%)	0
Viral infection	0/321 (0%)	0	1/958 (0.1%)	1
Injury, poisoning and procedural complications
Spinal compression fracture	0/321 (0%)	0	1/958 (0.1%)	1
Spinal fracture	0/321 (0%)	0	1/958 (0.1%)	1
Metabolism and nutrition disorders
Diabetes mellitus	0/321 (0%)	0	1/958 (0.1%)	1
Malnutrition	1/321 (0.3%)	1	0/958 (0%)	0
Type 2 diabetes mellitus	0/321 (0%)	0	1/958 (0.1%)	1
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis	0/321 (0%)	0	1/958 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/321 (0%)	0	1/958 (0.1%)	1
Uterine leiomyoma	0/321 (0%)	0	1/958 (0.1%)	1
Renal and urinary disorders
Renal colic	1/321 (0.3%)	1	0/958 (0%)	0
Reproductive system and breast disorders
Ovarian enlargement	0/321 (0%)	0	1/958 (0.1%)	1
Penile vein thrombosis	1/321 (0.3%)	1	0/958 (0%)	0
Vascular disorders
Arteriosclerosis	0/321 (0%)	0	1/958 (0.1%)	1
Deep vein thrombosis	1/321 (0.3%)	1	1/958 (0.1%)	1
Hypertension	0/321 (0%)	0	1/958 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Placebo IV Q4W		300 mg Mirikizumab IV Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/321 (5.6%)		31/958 (3.2%)
Blood and lymphatic system disorders
Anaemia	18/321 (5.6%)	18	31/958 (3.2%)	32

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.