An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02497469
• Collaborator: (none)
• Enrollment: 771
• Locations: 330
• Arms: 2
• Actual Duration (Months): 42.7
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) treatment compared to adalimumab subcutaneous (SC) treatment over a 52-week treatment period.

Condition or Disease	Intervention/Treatment	Phase
Colitis, Ulcerative	Drug: Vedolizumab; Drug: Adalimumab placebo; Drug: Adalimumab; Drug: Vedolizumab placebo	Phase 3

Detailed Description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have ulcerative colitis. This study will look at the stool frequency, rectal bleeding and findings on endoscopy of people who take vedolizumab compared to those who take adalimumab.

The study will enroll approximately 658 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Vedolizumab 300 mg IV

• Adalimumab 160 mg on Day 1 followed by 80 mg on Week 2 then 40 mg every 2 weeks SC

All participants will receive 1 intravenous infusion on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. All participants will also receive 4 SC injections on Day 1 or 2 SC injections each on Days 1 and 2, followed by 2 SC injections in 1 day on Week 2 and then 1 SC injection every 2 weeks for up to Week 50. All participants will be asked to record the symptoms of ulcerative colitis in a daily diary.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 79 weeks. Participants will make approximately 11 visits to the clinic, and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 771 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
• Actual Study Start Date: Jun 29, 2015
• Actual Primary Completion Date: Sep 26, 2018
• Actual Study Completion Date: Jan 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vedolizumab IV 300 mg Vedolizumab 300 milligram (mg), infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.	Drug: Vedolizumab; Vedolizumab infusion; Drug: Adalimumab placebo; Adalimumab placebo-matching injection
Active Comparator: Adalimumab SC 160/80/40 mg Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Drug: Adalimumab; Adalimumab injection; Drug: Vedolizumab placebo; Vedolizumab placebo-matching infusion

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Clinical Remission [Week 52]

   Clinical remission was defined as a complete Mayo score of ≤2 points and no individual subscore >1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).

Secondary Outcome Measures

1. Percentage of Participants Who Achieved Mucosal Healing [Week 52]

   Mucosal healing was defined as a Mayo score endoscopic subscore of <= 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).

2. Percentage of Participants Who Used Oral Corticosteroids at Baseline Who Discontinued Corticosteroids and Were in Clinical Remission [Week 52]

   Corticosteroid-free remission was defined as participants using oral corticosteroids at Baseline (Week 0) who had discontinued oral corticosteroids and were in clinical remission at Week 52. Clinical remission was defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Has a diagnosis of ulcerative colitis established at least 3 months prior to screening by clinical and endoscopic evidence and corroborated by a histopathology report.

2. Has moderately to severely active ulcerative colitis as determined by a Mayo score of 6 to 12 with an endoscopic subscore greater than or equal to >=2 within 14 days prior to the randomization.

3. Has evidence of ulcerative colitis proximal to the rectum (>=15 centimeter [cm] of involved colon).

4. With extensive colitis (up to the hepatic flexure) or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during the Screening Period).

5. The participant:

6. Has had previous treatment with tumor necrosis factor- alpha (TNF-alpha) antagonists without documented clinical response to treatment (example, due to lack of response [primary nonresponders], loss of response, or intolerance [secondary nonresponders]), or

7. Has previously used a TNF-alpha antagonists (except adalimumab), and discontinued its use due to reasons other than safety, or

8. Is naïve to TNF-alpha antagonist therapy but is failing current treatment (example, corticosteroids, 5-aminosalicylate [5-ASA], or immunomodulators).

Exclusion Criteria:

1. Clinical evidence of abdominal abscess or toxic megacolon at Screening.

2. Has had an extensive colonic resection, subtotal or total colectomy.

3. Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.

4. Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.

5. Has received any of the following for the treatment of underlying disease within 30 days of randomization:

6. Non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide) other than those specifically listed in Section Permitted Medications For Treatment of UC.

7. An approved non-biologic therapy in an investigational protocol.

8. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half lives prior to the screening (whichever is longer).

9. Has previously received natalizumab, efalizumab, adalimumab, AMG-181, anti-mucosal addressin cell adhesion molecule-1 antibodies, or rituximab.

10. Has previously received vedolizumab.

11. Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia.

12. Evidence of an active infection during Screening.

13. Evidence of, or treatment for, Clostridium difficile (C. difficile) or other intestinal pathogen within 28 days prior to the 1st dose of study drug.

14. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection (* HBV immune participants, ie, being hepatitis B surface antigen [HBsAg], may participate).

15. Has active or latent TB, regardless of treatment history.

16. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the 1st dose of study drug.

17. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IMC - Diagnostic and Medical Clinic	Mobile	Alabama	United States	36604
2	Arizona Arthritis & Rheumatology Research, PLLC	Phoenix	Arizona	United States	85037
3	Arkansas Primary Care Clinic, PA	Little Rock	Arkansas	United States	72204
4	WCCT Global (PH 1 Unit)	Costa Mesa	California	United States	92626
5	California Medical Research Associates Inc.	Northridge	California	United States	91324
6	Sutter Institute for Medical Research	Sacramento	California	United States	95816
7	Rocky Mountain Gastroenterology	Lakewood	Colorado	United States	80214-5434
8	Medical Research Center of Connecticut, LLC	Hamden	Connecticut	United States	06518
9	Innovative Medical Research of South Florida, Inc.	Aventura	Florida	United States	33180
10	Advanced Clinical Research of Miami	Doral	Florida	United States	33172
11	Wellness Clinical Research	Hialeah Gardens	Florida	United States	33016
12	Nature Coast Clinical Research, LLC	Inverness	Florida	United States	34452
13	Florida Center for Gastroenterology	Largo	Florida	United States	33773-1615
14	South Florida Research Phase I-IV	Miami Springs	Florida	United States	33166
15	Gastro Health	Miami	Florida	United States	33143
16	Medical Professional Clinical Research	Miami	Florida	United States	33165
17	Tellus Clinical Research, Inc.	Miami	Florida	United States	33173
18	Gastroenterology Group of Naples	Naples	Florida	United States	34102
19	Internal Medicine Specialists	Orlando	Florida	United States	32806
20	BRCR Medical Center, Inc.	Plantation	Florida	United States	33322
21	Clinical Research Center of Florida	Pompano Beach	Florida	United States	33060
22	Shafran Gastroenterology Center	Winter Park	Florida	United States	32789
23	Emory University Hospital	Atlanta	Georgia	United States	30322
24	Gastroenterology Associates of Central Georgia	Macon	Georgia	United States	31201
25	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
26	Rush University Medical Center	Chicago	Illinois	United States	60612
27	Carle Foundation Hospital	Urbana	Illinois	United States	61801
28	Gastroenterology of Southern Associates	New Albany	Indiana	United States	47150
29	Iowa Digestive Disease Center	Clive	Iowa	United States	50325
30	Cotton-O'Neil Clinical Research Center, Digestive Health	Topeka	Kansas	United States	66606
31	University of Louisville	Louisville	Kentucky	United States	40202
32	Research Concierge, LLC	Owensboro	Kentucky	United States	42303
33	Gastroenterology Associates, LLC	Baton Rouge	Louisiana	United States	70809
34	Lafayette General Medical Center	Lafayette	Louisiana	United States	70503
35	Clinical Trials Management, LLC	Metairie	Louisiana	United States	70006
36	Louisiana Research Center, LLC	Shreveport	Louisiana	United States	71103
37	Digestive Disease Associates	Catonsville	Maryland	United States	21228
38	Chevy Chase Clinical Research	Chevy Chase	Maryland	United States	20815
39	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan	United States	48047
40	Center for Digestive Health and Nutritional Excellence	Troy	Michigan	United States	48098
41	Gastroenterology Associates of Western Michigan, P.L.C.	Wyoming	Michigan	United States	49519
42	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
43	Digestive Health Center PA	Ocean Springs	Mississippi	United States	39564
44	Ehrhardt Clinical Research, LLC	Belton	Missouri	United States	64012
45	Truman Medical Centers, Inc.	Kansas City	Missouri	United States	64108
46	Alegent Creighton Clinic Gastroenterology	Omaha	Nebraska	United States	68124
47	AGA Clinical Research Associates, LLC	Egg Harbor Township	New Jersey	United States	08234
48	Long Island Clinical Research Associates	Great Neck	New York	United States	11021
49	Mount Sinai - PRIME	Lake Success	New York	United States	10029
50	Digestive Disease Care	New Hyde Park	New York	United States	11040
51	Premier Medical Group of the Hudson Valley, PC	Poughkeepsie	New York	United States	12601
52	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7080
53	Consultants for Clinical Research Inc.	Cincinnati	Ohio	United States	45219
54	Ohio State University Clinical Trials Management Office	Columbus	Ohio	United States	43210
55	Dayton Gastroenterology, Inc	Dayton	Ohio	United States	45415
56	Gastro-Enterology Research of Lima	Lima	Ohio	United States	45806
57	Options Health Research	Tulsa	Oklahoma	United States	74104
58	The Oregon Clinic-West Hills Gastroenterology	Portland	Oregon	United States	97225
59	Main Line Gastroenterology Associates	Malvern	Pennsylvania	United States	19355
60	Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
61	Invocare Clinical Research Center	West Columbia	South Carolina	United States	29169
62	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212-1375
63	Texas Digestive Disease Consultants - Dallas	Dallas	Texas	United States	75231
64	Baylor University Hospital	Dallas	Texas	United States	75246
65	MedResearch, Inc	El Paso	Texas	United States	79935
66	Gastroenterology Consultants of South Texas, PA	Harlingen	Texas	United States	78550
67	Gulf Coast Research Group LLC	Houston	Texas	United States	77098
68	Texas Digestive Disease Consultants - Irving	Irving	Texas	United States	75039
69	Advanced Clinical Research Associates	Plano	Texas	United States	75093
70	Gastroenterology Research of San Antonio, LLC	San Antonio	Texas	United States	78229
71	Texas Digestive Disease Consultants - Southlake	Southlake	Texas	United States	76092
72	Digestive Health Specialists of Tyler	Tyler	Texas	United States	75701
73	Gastroenterology Associates of Tidewater	Chesapeake	Virginia	United States	23320
74	Virginia Mason Seattle Main Clinic	Seattle	Washington	United States	98101
75	Wenatchee Valley Hospital & Clinics	Wenatchee	Washington	United States	98801
76	University of Wisconsin	Madison	Wisconsin	United States	53705
77	Allegiance Research Specialists, LLC	Milwaukee	Wisconsin	United States	53226
78	Instituto de Investigaciones Clinicas-Mar del Plata	Mar del Plata	Buenos Aires	Argentina	B7600FZ
79	Instituto Medico CER	Quilmes	Buenos Aires	Argentina	B1878DVB
80	Expertia S.A- Mautalen Salud e Investigacion	Ciudad Autonoma Buenos Aires		Argentina	C1128AAE
81	Centro de Investigaciones Clinicas Instituto del Corazon	Cordoba		Argentina	X5000EVQ
82	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
83	Mater Adult Hospital	South Brisbane	Queensland	Australia	4101
84	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
85	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
86	Tennyson Centre Day Hospital	Bedford Park	South Australia	Australia	5042
87	Ballarat Base Hospital	Ballarat	Victoria	Australia	3350
88	Monash Medical Centre Moorabbin	Clayton	Victoria	Australia	3168
89	St Frances Xavier Cabrini Hospital	Malvern	Victoria	Australia	3144
90	Universitair Ziekenhuis Gent	Gent		Belgium	9000
91	University Clinical Centre of the Republic of Srpska	Banja Luka		Bosnia and Herzegovina	78000
92	University Clinical Hospital Mostar	Mostar		Bosnia and Herzegovina	88000
93	University Clinic Centre Sarajevo	Sarajevo		Bosnia and Herzegovina	71000
94	MHAT - Pazardzhik AD	Pazardzhik		Bulgaria	4400
95	MHAT 'Avis Medica' OOD	Pleven		Bulgaria	5800
96	UMHAT 'Dr. Georgi Stranski', EAD	Pleven		Bulgaria	5800
97	MHAT "Hadzhi Dimitar", OOD	Sliven		Bulgaria	8800
98	"City Clinic UMHAC" EOOD	Sofia		Bulgaria	1407
99	Medical Center "Excelsior", OOD	Sofia		Bulgaria	1407
100	UMHAT "Sv. Ivan Rilski", EAD	Sofia		Bulgaria	1431
101	UMHAT 'Tsaritsa Yoanna - ISUL', EAD	Sofia		Bulgaria	1527
102	Fourth MHAT - Sofia EAD	Sofia		Bulgaria	1606
103	Military Medical Academy - MHAT - Sofia	Sofia		Bulgaria	1606
104	UMHAT 'Sveta Anna' AD	Sofia		Bulgaria	1750
105	Medical Center "Nov Rehabilitatsionen Tsentar", EOOD	Stara Zagora		Bulgaria	6000
106	MHAT 'Sv. Marina', EAD	Varna		Bulgaria	9020
107	University of Alberta	Edmonton	Alberta	Canada	T6G 2X8
108	McMaster University Health Sciences Center	Hamilton	Ontario	Canada	L8N3Z5
109	Hotel Dieu Hospital	Kingston	Ontario	Canada	K7L 5G2
110	LHSC - University Hospital	London	Ontario	Canada	N6A 5A5
111	LHSC - Victoria Hospital	London	Ontario	Canada	N6A 5W9
112	Toronto Digestive Disease Associates, Inc.	Vaughan	Ontario	Canada	L4L 4Y7
113	Royal University Hospital	Saskatoon	Saskatchewan	Canada	S7N 0W8
114	Fundacion Oftalmologica de Santander - FOSCAL	Floridablanca		Colombia	681004
115	Instituto de Coloproctologia ICO S.A.S.	Medellin		Colombia	050025
116	Clinical Hospital Centre Osijek	Osijek		Croatia	31000
117	General Hospital Pula	Pula		Croatia	52100
118	Polyclinic Medico	Rijeka		Croatia	51000
119	Clinical Hospital Center "Sestre Milosrdnice"	Zagreb		Croatia	10000
120	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
121	Clinical Hospital Dubrava	Zagreb		Croatia	10000
122	Clinical Hospital Merkur	Zagreb		Croatia	10000
123	CCBR - Brno - CZ	Brno		Czechia	60200
124	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia	65691
125	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove		Czechia	500 12
126	CCBR Czech, a.s	Pardubice		Czechia	530 02
127	A-Shine	Plzen		Czechia	31200
128	CCBR - Prague - CZ	Praha 3		Czechia	13000
129	Thomayerova nemocnice	Praha 4 - Krc		Czechia	140 59
130	Klinicke centrum ISCARE Lighthouse	Praha 7		Czechia	17004
131	Axon Clinical, s.r.o.	Praha 8		Czechia	182 00
132	Nordsjallands Hospital, Frederikssund	Frederikssund		Denmark	3600
133	Hvidovre_Hospital	Hvidovre		Denmark	2650
134	Koge Sygehus	Koge		Denmark	4600
135	Odense Universitetshospital	Odense C		Denmark	5000
136	West Tallinn Central Hospital	Tallinn		Estonia	10617
137	North Estonia Medical Centre Foundation	Tallinn		Estonia	13419
138	Tartu University Hospital	Tartu		Estonia	50406
139	CHU Nice - Hopital de l'Archet 2	Nice Cedex 3	Alpes Maritimes	France	06200
140	Hopital Nord - CHU Marseille	Marseille cedex 20	Bouches-du-Rhone	France	13915
141	Hopital Saint Joseph	Marseille	Bouches-du-Rhone	France	13008
142	Groupe Hospitalier Sud - Hopital Haut-Leveque	Pessac	Gironde	France	33604
143	CHU de Toulouse - Hopital Rangueil	Toulouse Cedex 09	Haute Garonne	France	31059
144	Hopital Beaujon	Clichy cedex	Hauts De Seine	France	92110
145	CHU Saint Etienne - Hopital Nord	Saint Etienne	Loire	France	42055
146	Hopital de Brabois Adultes	Vandoeuvre les Nancy	Meurthe Et Moselle	France	54511
147	Hopital Claude Huriez - CHU Lille	Lille cedex	Nord	France	59037
148	CHU Amiens - Hopital Sud	Amiens Cedex	Somme	France	80054
149	Centre Hospitalier Departemental Les Oudairies	La Roche S/ Yon Cedex 9	Vendee	France	85925
150	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg	Germany	69120
151	Universitaetsklinikum Tuebingen	Tuebingen	Baden Wuerttemberg	Germany	72076
152	Klinikum der Johann Wolfgang Goethe-Universitaet	Frankfurt	Hessen	Germany	60590
153	Universitaetsklinikum Koeln	Koeln	Nordrhein Westfalen	Germany	50937
154	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz	Rheinland Pfalz	Germany	55131
155	Universitaetsklinikum Magdeburg A.oe.R	Magdeburg	Sachsen Anhalt	Germany	39120
156	EUGASTRO GmbH	Leipzig	Sachsen	Germany	04103
157	Universitaetsklinikum Schleswig-Holstein - Campus Kiel	Kiel	Schleswig Holstein	Germany	24105
158	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Lubeck	Schleswig Holstein	Germany	23538
159	Charite - Campus Virchow-Klinikum	Berlin		Germany	13353
160	Krankenhaus Waldfriede e. V.	Berlin		Germany	141 63
161	Asklepios Klinik Hamburg	Hamburg		Germany	22559
162	The University of Hong Kong	Hong Kong		Hong Kong
163	Tuen Mun Hospital	Medicine & Geriatrics		Hong Kong	00000
164	The Chinese University of Hong Kong	Shatin		Hong Kong	00000
165	Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza	Bekescsaba		Hungary	5600
166	Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont	Budapest		Hungary	1076
167	Semmelweis Egyetem	Budapest		Hungary	1083
168	Semmelweis Egyetem	Budapest		Hungary	1088
169	Pannonia Maganorvosi Centrum	Budapest		Hungary	1136
170	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
171	Markhot Ferenc Oktatokorhaz es Rendelointezet	Eger		Hungary	3300
172	Pecsi Tudomanyegyetem	Pecs		Hungary	7624
173	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary	6720
174	Tolna Megyei Balassa Janos Korhaz	Szekszard		Hungary	7100
175	HaEmek Medical Center	Afula		Israel	18101
176	Barzilai Medical Center	Ashkelon		Israel	78278
177	Hillel Yaffe Medical	Hadera		Israel	3810101
178	Wolfson Medical Center	Holon		Israel	58100
179	Shaare Zedek Medical Center	Jerusalem		Israel	91031
180	Clalit Health Services-Lev Talpiyot	Jerusalem		Israel	9362410
181	Meir Medical Center	Kfar- Saba		Israel	4428164
182	Galilee Medical Center	Nahariya		Israel	22100
183	Chaim Sheba Medical Center	Ramat Gan		Israel	5265601
184	Kaplan Medical Center	Rechovot		Israel	7610001
185	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
186	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia	Italy	71013
187	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
188	I.R.C.C.S Policlinico San Donato	San Donato Milanese	Milano	Italy	20097
189	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
190	Azienda Ospedaliera Ospedale Cannizzaro	Catania		Italy	95100
191	Azienda Ospedaliero Universitaria San Martino	Genova		Italy	16132
192	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina		Italy	98125
193	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano		Italy	20157
194	A.O.U. Policlinico di Modena	Modena		Italy	41124
195	Azienda Ospedaliera Universitaria "Federico II"	Napoli		Italy	80131
196	Seconda Universita degli Studi di Napoli	Napoli		Italy	80131
197	Azienda Ospedaliera di Padova	Padova		Italy	35128
198	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo		Italy	90127
199	Azienda Ospedaliera Vincenzo Cervello	Palermo		Italy	90146
200	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56124
201	Azienda Ospedaliera San Camillo Forlanini	Roma		Italy	00152
202	Hanyang Univerisy Guri Hospital	Guri-si	Gyeonggi-do	Korea, Republic of	11923
203	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
204	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16247
205	Kyungpook National University Hospital	Daegu	Gyeongsangbuk-do	Korea, Republic of	700-721
206	Pusan National University Hospital	Busan		Korea, Republic of	49241
207	Yeungnam University Hospital	Daegu		Korea, Republic of	42415
208	Kyung Hee University Hospital	Seoul		Korea, Republic of	02447
209	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
210	Seoul National University Hospital	Seoul		Korea, Republic of	03080
211	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
212	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	03722
213	Asan Medical Center	Seoul		Korea, Republic of	05505
214	Samsung Medical Center	Seoul		Korea, Republic of	06351
215	The Catholic University of Korea, Seoul St. Marys Hospital	Seoul		Korea, Republic of	06591
216	Digestive Diseases Center "Gastro"	Riga		Latvia	LV-1006
217	Pauls Stradins Clinical University Hospital SLLC	Riga		Latvia	LV1002
218	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas		Lithuania	50009
219	Klaipeda Republican Hospital, Public Institution	Klaipeda		Lithuania	92231
220	Klaipeda University Hospital, Public Institution	Klaipeda		Lithuania	92288
221	Vilnius University Hospital Santariskiu Clinic, Public Institution	Vilnius		Lithuania	LT-08661
222	Morales Vargas Centro de Investigacion, S.C.	Leon	Guanajuato	Mexico	37000
223	Centro de Investigacion Farmacologica del Bajio, S.C.	Leon	Guanajuato	Mexico	37520
224	Christus Muguerza Sur S.A. de C.V.	Monterrey	Nuevo Leon	Mexico	64908
225	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango		Mexico	34000
226	Sociedad de Metabolismo y Corazon S.C	Veracruz		Mexico	91910
227	Onze Lieve Vrouwe Gasthuis, Locatie Oost	Amsterdam		Netherlands	1091 AC
228	Academisch Medisch Centrum	Amsterdam		Netherlands	1105 AZ
229	Universitair Medisch Centrum Groningen (UMCG)	Groningen		Netherlands	9713 GZ
230	Maastricht University Medical Center	Maastricht		Netherlands	6202 AZ
231	Erasmus Medisch Centrum	Rotterdam		Netherlands	3015 CE
232	SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego	Bialystok		Poland	15-275
233	NZOZ Vitamed	Bydgoszcz		Poland	85-079
234	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
235	SP CSK im. prof. K. Gibinskiego SUM	Katowice		Poland	40-752
236	Gabinet Endoskopii Przewodu Pokarmowego	Krakow		Poland	31-009
237	SPZOZ Uniwersytecki Szpital Klin. nr 1 im.N.Barlickiego UM	Lodz		Poland	90-153
238	Santa Familia Centrum Badan, Profilaktyki i Leczenia	Lodz		Poland	90-302
239	GASTROMED Sp. z o.o.	Lublin		Poland	20-582
240	SOLUMED Centrum Medyczne	Poznan		Poland	60-529
241	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin		Poland	71-434
242	Centrum Zdrowia Matki, Dziecka i Mlodziezy	Warszawa		Poland	00-632
243	Centralny Szpital Kliniczny MSW w Warszawie	Warszawa		Poland	02-507
244	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Warszawa		Poland	02-781
245	Nzoz Vivamed	Warszawa		Poland	03-580
246	LexMedica Osrodek Badan Klinicznych	Wroclaw		Poland	53-114
247	Ars-Medica S.C Rybak Maria, Rybak Zbigniew	Wroclaw		Poland	53-333
248	EuroMediCare Szpital Specjalistyczny z Przychodni we Wroclawiu	Wroclaw		Poland	54-144
249	Hospital de Braga	Braga		Portugal	4710-243
250	Centro Hospitalar e Universitario de Coimbra E.P.E	Coimbra		Portugal	3000-075
251	Centro Hospitalar Cova da Beira	Covilha		Portugal	6200-502
252	Hospital da Senhora da Oliveira Guimaraes	Guimaraes		Portugal	4835-044
253	Centro Hospitalar do Alto Minho - Unidade Local de Saude do Alto Minho, EPE	Viana do Castelo		Portugal	4904-858
254	Centro Hospitalar Vila Nova de Gaia/Espinho, E.P.E	Vila Nova de Gaia		Portugal	4434-502
255	Spitalul Clinic Colentina	Bucuresti		Romania	020125
256	Institutul Clinic Fundeni	Bucuresti		Romania	022328
257	S.C Centrul de Gastroenterologie Dr. Goldis S.R.L	Timisoara		Romania	300002
258	SBEI HPE "Kazan State Medical University" of the MoH of the RF	Kazan		Russian Federation	420012
259	TSBIH "Territorial Clinical Hospital"	Krasnoyarsk		Russian Federation	660022
260	Research Institute of Gastroenterology	Moscow		Russian Federation	111123
261	FSBIH "Central Clinical Hospital of Russian Academy of Sciences"	Moscow		Russian Federation	119333
262	FSBI State Scientific Centre of Coloproctology" of the MoH of RF	Moscow		Russian Federation	123154
263	SBIH of Nizhniy Novgorod region " Nizhniy Novgorod Regional Clinical Hospital n.a. N.A. Semashko"	Nizhny Novgorod		Russian Federation	603126
264	SBEIHPE Novosibirsk State Medical University	Novosibirsk		Russian Federation	630091
265	FSBI "Scientific Research Institute of Physyology and Basic Medicine" under the SB of RAMS	Novosibirsk		Russian Federation	630117
266	BHI of Omsk region Clinical Oncology Dispensary	Omsk		Russian Federation	644013
267	SBEI of HPE "Omsk SMA" SBEI HPE "Omsk State Medical University" of the MoH of the RF	Omsk		Russian Federation	644099
268	SBEI HPE "Rostov State Medical University" of the MoH of the RF	Rostov-on-Don		Russian Federation	344022
269	FSMEI HPE Military Medical Academy n.a. S.M.Kirov"of Ministry of Defense of Russia	Saint-Petersburg		Russian Federation	194044
270	SPb SBIH "City Hospital # 26"	Saint-Petersburg		Russian Federation	196247
271	SPb SBIH "City Hospital # 9"	Saint-Petersburg		Russian Federation	197110
272	Private Educational Institution of Higher Education "Medical University "REAVIZ"	Samara		Russian Federation	443115
273	SIH "Regional Clinical Hospital "	Saratov		Russian Federation	410053
274	SPb SBIH "City Hospital # 40 of Kurortnyi region"	Sestroretsk		Russian Federation	197706
275	RSBIH "Smolensk Regional Clinical Hospital"	Smolensk		Russian Federation	214019
276	SPb SBIH "City Hospital of Saint Martyr Elizaveta"	St. Petersburg		Russian Federation	195257
277	SBIH of Yaroslavl region " Regional Clinical Hospital "	Yaroslavl		Russian Federation	150062
278	Clinical Center of Serbia	Belgrade		Serbia	11000
279	Clinical Center Zvezdara	Belgrade		Serbia	11000
280	Clinical Center Bezanijska kosa	Belgrade		Serbia	11080
281	Clinical Center Zemun	Belgrade		Serbia	11080
282	Clinical Center Kragujevac	Kragujevac		Serbia	34000
283	Clinical Center Nis	Nis		Serbia	18000
284	Clinical Center of Vojvodina	Novi Sad		Serbia	21000
285	IBDcentrum s.r.o.	Bratislava		Slovakia	81108
286	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Bratislava		Slovakia	82606
287	Gastroped s.r.o.	Kosice		Slovakia	04001
288	KM Management spol. s r.o.	Nitra		Slovakia	949 01
289	Gastro I, s.r.o.	Presov		Slovakia	080 01
290	Frantisek Horvath- GEA	Sahy		Slovakia	936 01
291	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
292	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
293	Hospital General Universitario de Alicante	Alicante		Spain	03010
294	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
295	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
296	Chung Shan Medical University Hospital	Taichung		Taiwan	402
297	National Taiwan University Hospital	Taipei		Taiwan	100
298	Mackay Memorial Hospital	Taipei		Taiwan	10449
299	Ankara University Medical Faculty	Ankara		Turkey	06100
300	Acibadem Fulya Hospital	Istanbul		Turkey	34349
301	Haydarpasa Numune Training and Research Hospital	Istanbul		Turkey	34668
302	Marmara University Pendik Research and Training Hospital	Istanbul		Turkey	34899
303	Kocaeli Derince Training and Research Hospital	Kocaeli		Turkey	41380
304	Mersin University Medical Faculty	Mersin		Turkey	33343
305	RCI Chernivtsi RCH Dep of Surgery Bukovinian SMU	Chernivtsi		Ukraine	58002
306	SI Institute of Gastroenterology of NAMSU Dept of Stomach & Duodenum Diseases, D&ThN SI DMA of MoHU	Dnipropetrovsk		Ukraine	49074
307	Regional CH Dep of Gastroenterology SHEI Ivano-Frankivsk NMU	Ivano-Frankivsk		Ukraine	76008
308	CI of PH Kharkiv CCH #2	Kharkiv		Ukraine	61037
309	CI A.and O. Tropiny City Clinical Hospital	Kherson		Ukraine	73000
310	Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus	Kirovohrad		Ukraine	25006
311	CI of Kyiv RC Kyiv Regional Clinical Hospital	Kyiv		Ukraine	01023
312	MI of Healthcare Kyiv RCH P.L. Shupyk NMA of PGE	Kyiv		Ukraine	01023
313	Kyiv CCH #12 Dept of Therapy O.O.Bogomolets NMU	Kyiv		Ukraine	01103
314	Kyiv CCH #8 Dept of Gastroenterology P.L. Shupyk NMA of PGE	Kyiv		Ukraine	04201
315	CI of TRC Ternopil University Hospital	Lviv		Ukraine	46002
316	Communal City Clinical Hospital of Ambulance, Dept of Therapy #1 D.Halytskyi Lviv NMU	Lviv		Ukraine	79059
317	CI Odesa Regional Clinical Hospital	Odesa		Ukraine	65025
318	SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU	Uzhgorod		Ukraine	88009
319	Private Small Enterprise Medical Center Pulse	Vinnytsia		Ukraine	21001
320	Vinnytsya RCH for Patriotic War Invalides Therapeutic Dept # 1 Vinnytsia M.I.Pyrogov NMU	Vinnytsia		Ukraine	21005
321	MCIC MC LLC Health Clinic	Vinnytsia		Ukraine	21029
322	SRI of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU	Vinnytsia		Ukraine	21029
323	CI City Clinical Hospital #6 Dept of Gastroenterology	Zaporizhzhia		Ukraine	69035
324	SI Branch CH of Zaporizhzhia Station-2 of SE Prydniprovska Railway Dept of Surgery Zaporizhzhia SMU	Zaporizhzhia		Ukraine	69104
325	Derriford Hospital	Plymouth	Devon	United Kingdom	PL6 5FP
326	Salford Royal	Salford	Greater Manchester	United Kingdom	M6 8HD
327	Norfolk and Norwich University Hospital	Norwich	Norfolk	United Kingdom	NR47UY
328	Glasgow Royal Infirmary	Glasgow	Strathclyde	United Kingdom	G4 0SF
329	University Hospital Coventry	Coventry	West Midlands	United Kingdom	CV2 2DX
330	Royal Wolverhampton hospital	Wolverhampton	West Midlands	United Kingdom	WV10 0QP

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Feb 26, 2014
• Statistical Analysis Plan - Oct 18, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02497469
• Other Study ID Numbers: MLN0002-3026; U1111-1168-6713; 2015-000939-33; NL54690.056.15
• First Posted: Jul 14, 2015
• Last Update Posted: Jan 28, 2020
• Last Verified: Jan 1, 2020

• 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 Takeda: Drug Therapy
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Adalimumab; Vedolizumab

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 205 investigative sites worldwide from 29 June 2015 up to 18 January 2019.
Pre-assignment Detail	Participants with a diagnosis of moderately to severely active ulcerative colitis (UC) were enrolled in a 1:1 ratio to receive vedolizumab or adalimumab and matching placebo.

Arm/Group Title	Adalimumab SC, 160/80/40 mg	Vedolizumab IV 300 mg
Arm/Group Description	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Vedolizumab 300 mg, infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
Period Title: Overall Study
STARTED	386	385
Safety Analysis Set	386	383
COMPLETED	217	270
NOT COMPLETED	169	115

Baseline Characteristics

Arm/Group Title	Adalimumab SC, 160/80/40 mg	Vedolizumab IV 300 mg	Total
Arm/Group Description	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Vedolizumab 300 mg, infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.	Total of all reporting groups
Overall Participants	386	385	771
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.5 (13.44)	40.8 (13.74)	40.7 (13.59)
Sex: Female, Male (Count of Participants)
Female	170 44%	151 39.2%	321 41.6%
Male	216 56%	234 60.8%	450 58.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 1.6%	8 2.1%	14 1.8%
Not Hispanic or Latino	39 10.1%	23 6%	62 8%
Unknown or Not Reported	341 88.3%	354 91.9%	695 90.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	11 2.8%	4 1%	15 1.9%
Asian	30 7.8%	32 8.3%	62 8%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.1%
Black or African American	3 0.8%	2 0.5%	5 0.6%
White	341 88.3%	345 89.6%	686 89%
More than one race	0 0%	2 0.5%	2 0.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Australia	3 0.8%	5 1.3%	8 1%
Hong Kong	1 0.3%	4 1%	5 0.6%
Korea, Republic Of	19 4.9%	16 4.2%	35 4.5%
Taiwan, Province Of China	4 1%	1 0.3%	5 0.6%
Czech Republic	13 3.4%	8 2.1%	21 2.7%
Hungary	16 4.1%	16 4.2%	32 4.2%
Poland	78 20.2%	85 22.1%	163 21.1%
Serbia	11 2.8%	18 4.7%	29 3.8%
Slovakia	5 1.3%	8 2.1%	13 1.7%
Bosnia	2 0.5%	1 0.3%	3 0.4%
Bulgaria	10 2.6%	6 1.6%	16 2.1%
Croatia	11 2.8%	5 1.3%	16 2.1%
Israel	9 2.3%	13 3.4%	22 2.9%
Romania	6 1.6%	6 1.6%	12 1.6%
Russia	41 10.6%	44 11.4%	85 11%
Turkey	9 2.3%	5 1.3%	14 1.8%
Ukraine	26 6.7%	39 10.1%	65 8.4%
Canada	18 4.7%	20 5.2%	38 4.9%
United States	42 10.9%	29 7.5%	71 9.2%
Argentina	1 0.3%	3 0.8%	4 0.5%
Colombia	2 0.5%	2 0.5%	4 0.5%
Mexico	9 2.3%	3 0.8%	12 1.6%
France	4 1%	6 1.6%	10 1.3%
Germany	3 0.8%	6 1.6%	9 1.2%
Italy	9 2.3%	11 2.9%	20 2.6%
Latvia	6 1.6%	7 1.8%	13 1.7%
Lithuania	7 1.8%	7 1.8%	14 1.8%
Portugal	9 2.3%	4 1%	13 1.7%
United Kingdom	2 0.5%	3 0.8%	5 0.6%
Denmark	8 2.1%	3 0.8%	11 1.4%
Belgium	0 0%	1 0.3%	1 0.1%
Netherlands	1 0.3%	0 0%	1 0.1%
Spain	1 0.3%	0 0%	1 0.1%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	170.5 (9.65)	172.0 (9.90)	171.3 (9.79)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.43 (18.374)	72.67 (16.952)	73.05 (17.673)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.17 (5.646)	24.46 (4.786)	24.82 (5.244)
Smoking Classification (Count of Participants)
Has Never Smoked	259 67.1%	280 72.7%	539 69.9%
Is a Current Smoker	23 6%	19 4.9%	42 5.4%
Is an Ex-smoker	104 26.9%	84 21.8%	188 24.4%
Missing	0 0%	2 0.5%	2 0.3%
Female Reproductive Status (Count of Participants)
Postmenopausal	29 7.5%	32 8.3%	61 7.9%
Surgically Sterile	18 4.7%	17 4.4%	35 4.5%
Female of Childbearing Potential	123 31.9%	102 26.5%	225 29.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission
Description	Clinical remission was defined as a complete Mayo score of ≤2 points and no individual subscore >1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Adalimumab SC, 160/80/40 mg	Vedolizumab IV 300 mg
Arm/Group Description	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Vedolizumab 300 mg, infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
Measure Participants	386	383
Number (95% Confidence Interval) [percentage of participants]	22.5 5.8%	31.3 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab SC, 160/80/40 mg, Vedolizumab IV 300 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0061
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	8.8
	Confidence Interval	(2-Sided) 95%; 2.5 to 15.0
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		P-value of the adjusted difference was based on the Cochran-Mantel-Haenszel method, stratified by concomitant use of oral corticosteroids (Yes/No) and prior use of TNF-alpha antagonist (Yes/No) or the Fisher's exact method if the numerator was <=5.

2. Secondary Outcome

Title	Percentage of Participants Who Achieved Mucosal Healing
Description	Mucosal healing was defined as a Mayo score endoscopic subscore of <= 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Adalimumab SC, 160/80/40 mg	Vedolizumab IV 300 mg
Arm/Group Description	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Vedolizumab 300 mg, infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
Measure Participants	386	383
Number (95% Confidence Interval) [percentage of participants]	27.7 7.2%	39.7 10.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab SC, 160/80/40 mg, Vedolizumab IV 300 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95%; 5.3 to 18.5
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		P-value of the adjusted difference was based on the Cochran-Mantel-Haenszel method, stratified by concomitant use of oral corticosteroids (Yes/No) and prior use of TNF-alpha antagonist (Yes/No) or the Fisher's exact method if the numerator was <=5.

3. Secondary Outcome

Title	Percentage of Participants Who Used Oral Corticosteroids at Baseline Who Discontinued Corticosteroids and Were in Clinical Remission
Description	Corticosteroid-free remission was defined as participants using oral corticosteroids at Baseline (Week 0) who had discontinued oral corticosteroids and were in clinical remission at Week 52. Clinical remission was defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Particiopants from, FAS, included all randomized participants who received at least 1 dose of study drug who used who used oral corticosteroids at Baseline.

Arm/Group Title	Adalimumab SC, 160/80/40 mg	Vedolizumab IV 300 mg
Arm/Group Description	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Vedolizumab 300 mg, infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
Measure Participants	119	111
Number (95% Confidence Interval) [percentage of participants]	21.8 5.6%	12.6 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adalimumab SC, 160/80/40 mg, Vedolizumab IV 300 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0641
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-9.3
	Confidence Interval	(2-Sided) 95%; -18.9 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		P-value of the adjusted difference was based on the Cochran-Mantel-Haenszel method, stratified by prior use of TNF-alpha antagonist (Yes/No) or the Fisher's exact method if the numerator was <=5.

Adverse Events

Time Frame	From first dose of study drug and up to 126 days after the last dose (Up to 68 weeks)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. The safety analysis set included all participants who received at least 1 dose of study drug. Participants were analyzed according to the treatment they actually received.
Arm/Group Title	Adalimumab SC, 160/80/40 mg		Vedolizumab IV 300 mg
Arm/Group Description	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.		Vedolizumab 300 mg, infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
All Cause Mortality
	Adalimumab SC, 160/80/40 mg		Vedolizumab IV 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/386 (0%)		1/383 (0.3%)
Serious Adverse Events
	Adalimumab SC, 160/80/40 mg		Vedolizumab IV 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/386 (13.7%)		42/383 (11%)
Blood and lymphatic system disorders
Anaemia	4/386 (1%)		1/383 (0.3%)
Cardiac disorders
Angina pectoris	0/386 (0%)		1/383 (0.3%)
Myocardial ischaemia	1/386 (0.3%)		0/383 (0%)
Pericarditis	0/386 (0%)		1/383 (0.3%)
Eye disorders
Blindness	0/386 (0%)		1/383 (0.3%)
Gastrointestinal disorders
Large intestine polyp	1/386 (0.3%)		0/383 (0%)
Colitis ulcerative	25/386 (6.5%)		19/383 (5%)
Colitis	1/386 (0.3%)		0/383 (0%)
Inflammatory bowel disease	1/386 (0.3%)		0/383 (0%)
Diarrhoea	0/386 (0%)		2/383 (0.5%)
Small intestinal obstruction	0/386 (0%)		1/383 (0.3%)
Abdominal pain	1/386 (0.3%)		3/383 (0.8%)
Ileus	0/386 (0%)		1/383 (0.3%)
Inguinal hernia	1/386 (0.3%)		1/383 (0.3%)
Peritoneal haemorrhage	1/386 (0.3%)		0/383 (0%)
Proctitis	0/386 (0%)		1/383 (0.3%)
Umbilical hernia	1/386 (0.3%)		0/383 (0%)
Incarcerated umbilical hernia	1/386 (0.3%)		0/383 (0%)
General disorders
Therapeutic response decreased	1/386 (0.3%)		0/383 (0%)
Immune system disorders
Drug hypersensitivity	1/386 (0.3%)		0/383 (0%)
Infections and infestations
Appendicitis	1/386 (0.3%)		1/383 (0.3%)
Anal abscess	1/386 (0.3%)		0/383 (0%)
Clostridium difficile colitis	0/386 (0%)		1/383 (0.3%)
Clostridium difficile infection	0/386 (0%)		1/383 (0.3%)
Cytomegalovirus infection	1/386 (0.3%)		3/383 (0.8%)
Liver abscess	1/386 (0.3%)		0/383 (0%)
Varicella	1/386 (0.3%)		0/383 (0%)
Wound infection	1/386 (0.3%)		0/383 (0%)
Pneumonia	2/386 (0.5%)		0/383 (0%)
Gastroenteritis viral	0/386 (0%)		1/383 (0.3%)
Injury, poisoning and procedural complications
Traumatic haemothorax	1/386 (0.3%)		0/383 (0%)
Ankle fracture	1/386 (0.3%)		0/383 (0%)
Stab wound	1/386 (0.3%)		0/383 (0%)
Post procedural complication	0/386 (0%)		1/383 (0.3%)
Thoracic vertebral fracture	0/386 (0%)		1/383 (0.3%)
Gamma-glutamyltransferase increased	1/386 (0.3%)		1/383 (0.3%)
Investigations
Alanine aminotransferase increased	0/386 (0%)		1/383 (0.3%)
Aspartate aminotransferase increased	0/386 (0%)		1/383 (0.3%)
Blood alkaline phosphatase increased	1/386 (0.3%)		0/383 (0%)
Metabolism and nutrition disorders
Hyponatraemia	1/386 (0.3%)		0/383 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/386 (0%)		2/383 (0.5%)
Muscular weakness	1/386 (0.3%)		0/383 (0%)
Pain in extremity	1/386 (0.3%)		0/383 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/386 (0%)		1/383 (0.3%)
Nervous system disorders
Brain stem haemorrhage	1/386 (0.3%)		0/383 (0%)
Cerebrovascular accident	1/386 (0.3%)		0/383 (0%)
Dysgraphia	0/386 (0%)		1/383 (0.3%)
Seizure	0/386 (0%)		1/383 (0.3%)
Nerve root compression	0/386 (0%)		2/383 (0.5%)
Psychiatric disorders
Major depression	0/386 (0%)		1/383 (0.3%)
Renal and urinary disorders
Acute kidney injury	1/386 (0.3%)		0/383 (0%)
Ureterolithiasis	0/386 (0%)		1/383 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/386 (0.3%)		0/383 (0%)
Pneumothorax spontaneous	0/386 (0%)		1/383 (0.3%)
Skin and subcutaneous tissue disorders
Dermatitis	0/386 (0%)		1/383 (0.3%)
Psoriasis	1/386 (0.3%)		0/383 (0%)
Vascular disorders
Hypovolaemic shock	1/386 (0.3%)		0/383 (0%)
Thrombophlebitis superficial	1/386 (0.3%)		1/383 (0.3%)
Other (Not Including Serious) Adverse Events
	Adalimumab SC, 160/80/40 mg		Vedolizumab IV 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	114/386 (29.5%)		103/383 (26.9%)
Blood and lymphatic system disorders
Anaemia	23/386 (6%)		19/383 (5%)
Gastrointestinal disorders
Colitis ulcerative	42/386 (10.9%)		26/383 (6.8%)
Infections and infestations
Nasopharyngitis	30/386 (7.8%)		27/383 (7%)
Upper respiratory tract infection	17/386 (4.4%)		20/383 (5.2%)
Nervous system disorders
Headache	21/386 (5.4%)		27/383 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.