GARDENIA: A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02136069
• Collaborator: (none)
• Enrollment: 397
• Locations: 119
• Arms: 2
• Actual Duration (Months): 66
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then once every 8 weeks [Q8W]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Etrolizumab; Drug: Infliximab; Other: Placebo (IV); Other: Placebo (Injection)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 397 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study to Evaluate the Efficacy and Safety of Etrolizumab Compared With Infliximab in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors
• Actual Study Start Date: Dec 24, 2014
• Actual Primary Completion Date: Jun 23, 2020
• Actual Study Completion Date: Jun 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etrolizumab + Placebo (IV) Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Drug: Etrolizumab; 105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.; Other Names: PRO145223 RO5490261 RG7413 ; Other: Placebo (IV); Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.
Active Comparator: Infliximab + Placebo (Injection) Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.	Drug: Infliximab; 5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.; Other: Placebo (Injection); Administered by SC injection Q4W until Week 52

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS) [Week 10, Week 54]

   Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Clinical Remission is MCS ≤2 with individual subscores ≤1.

Secondary Outcome Measures

1. Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1 [Week 10]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.

2. Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS [Week 54]

   Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.

3. Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS [Week 10 and Week 54]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.

4. Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS [Week 10 and Week 54]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

5. Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS [Baseline to Week 10]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.

6. Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS [Baseline to Week 54]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.

7. Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS [Baseline to Week 10, Week 54]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.

8. Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS [Week 54]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Endoscopic Remission is Endoscopy subscore = 0.

9. Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS [Week 10]

   MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

10. Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS [Week 10, Week 54]

    MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

11. Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [Week 54]

    MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.

12. Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) [Baseline until the end of study (up to 66 weeks)]

    All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.

13. Number of Participants With Adverse Events Leading to Study Drug Discontinuation [Baseline until the end of study (up to 66 weeks)]

14. Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 [Baseline until the end of study (up to 66 weeks)]

    All AEs were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.

15. Number of Participants With Serious Infection-Related Adverse Events [Baseline until the end of study (up to 66 weeks)]

16. Number of Participants With Malignancies [Baseline until the end of study (up to 66 weeks)]

17. Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 [Baseline until the end of study (up to 66 weeks)]

    All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.

18. Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 [Baseline until the end of study (up to 66 weeks)]

    All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.

19. Pharmacokinetics: Etrolizumab Serum Concentration [Weeks 2, 10, 12, 30, and 54]

20. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 [Weeks 10, 30, and 54]

    The IBDQ is used to assess participant's health-related quality of life (QOL). The 32-item questionnaire contains four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale with a higher score indicating better health-related QOL. IBDQ score is a total score summed up from across all 32 questions on the questionnaire. The score can range from 32-224 and the higher score indicates a better quality of life.

21. Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab [Weeks 0, 4, 10, 12, 30, and 54]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)

• Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)

• An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment

• Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period

• Use of highly effective contraception during and at least 24 weeks after the last dose of study drug

Exclusion Criteria:

• A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps

• Prior or planned surgery for UC

• Past or present ileostomy or colostomy

• Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, efalizumab, and tofactinib)

• History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients

• Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LKH - Universitätsklinikum der PMU Salzburg	Salzburg		Austria	5020
2	GZA Ziekenhuizen - Campus Sint-Vincentius	Antwerpen		Belgium	2018
3	Imeldaziekenhuis	Bonheiden		Belgium	2820
4	CHU St Pierre (St Pierre)	Brussels		Belgium	1000
5	Universitair Ziekenhuis Brussel; Neurology	Bruxelles		Belgium	1090
6	Cliniques Universitaires Saint-Luc; Pharmacy	Bruxelles		Belgium	1200
7	UZ Gent	Gent		Belgium	9000
8	AZ Sint Elisabeth Herentals	Herentals		Belgium	2200
9	University of Calgary; Heritage Medical Research Clinic	Calgary	Alberta	Canada	T2N 4Z6
10	Zeidler Ledcor Centre - University of Alberta; Division of Gasroenterology	Edmonton	Alberta	Canada	T6G 2X8
11	Guelph GI & Surgery Clinic	Guelph	Ontario	Canada	N1H 3R3
12	Centre de santé et de services sociaux Champlain-Charles-Le Moyne	Greenfield Park	Quebec	Canada	J4V 2H1
13	Hôpital Maisonneuve - Rosemont	Montreal	Quebec	Canada	H1T 2M4
14	Royal University Hospital	Saskatoon	Saskatchewan	Canada	S7N 0W8
15	Vojenska nemocnice Brno	Brno		Czechia	636 00
16	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
17	Oblastni nemocnice Kladno, a.s., nemocnice Stredoces. kraje; Endoskopicke centrum	Kladno		Czechia	272 59
18	Mestska Nemocnice Ostrava	Ostrava		Czechia	728 80
19	Pardubicka krajska nemocnice, a.s.	Pardubice		Czechia	532 03
20	ISCARE a.s.	Praha 7		Czechia	170 04
21	Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z., Ocni oddeleni	Usti Nad Labem		Czechia	401 13
22	Krajska nemocnice T. Bati, a.s.	Zlin		Czechia	76001
23	CHU de Caen - Hopital Cote de Nacre	Caen		France	14033
24	CHU Tours - Hôpital Trousseau	Chambray les Tours		France	37170
25	CHU Clermont Ferrand - Hôtel Dieu	Clermont-Ferrand		France	63000
26	Hôpital Beaujon	Clichy cedex		France	92110
27	CHU Hopital Saint Eloi	Montpellier		France	34295
28	CHU Nice - Hopital de l'Archet 2	Nice		France	06202
29	Centre Hospitalier Lyon Sud; Service de Gastro-Enterologie	Pierre-Benite		France	69495
30	Hôpital de Brabois Adultes	Vandoeuvre-les-nancy		France	54511
31	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin		Germany	12200
32	DRK Kliniken Berlin Westend	Berlin		Germany	14050
33	Krankenhaus Waldfriede e. V.	Berlin		Germany	14163
34	Universitätsklinikum Freiburg; Innere Medizin I; Hämatologie, Onkologie und Stammzelltransplantation	Freiburg		Germany	79106
35	Gastroenterologie Eppendorfer Baum	Hamburg		Germany	20249
36	Universitaetsklinikum Schleswig-Holstein, Campus Kiel	Kiel		Germany	24116
37	Universitätsklinikum Koeln	Koeln		Germany	50937
38	Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza	Bekescsaba		Hungary	5600
39	Semmelweis Egyetem	Budapest		Hungary	1083
40	Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz es Szakrendelo	Budapest		Hungary	1125
41	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest		Hungary	H-1077
42	Vasutegeszsegugyi Nonprofit KiemeltenKozhasznu Kft	Debrecen		Hungary	4025
43	Markhot Ferenc Oktato Korhaz es Rendelointezet	Eger		Hungary	3300
44	Petz Aladar Megyei Oktato Korhaz	Gyor		Hungary	9024
45	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz; II. Belgyogyaszat	Miskolc		Hungary	3526
46	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary	6720
47	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár		Hungary	8000
48	Rabin Medical Center-Beilinson Campus	Petach Tikva		Israel	4941492
49	Chaim Sheba Medical Center; Pediatrics B North and Pediatric Endocrinology Unit	Tel Hashomer		Israel	52621
50	Azienda Ospedaliero Universitaria di Parma	Parma	Emilia-Romagna	Italy	43100
51	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma	Lazio	Italy	00133
52	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio	Italy	00152
53	Asst Fatebenefratelli Sacco (Fatebenefratelli)	Milano	Lombardia	Italy	20121
54	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano	Lombardia	Italy	20162
55	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano	Lombardia	Italy
56	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia	Italy	20089
57	I.R.C.C.S Policlinico San Donato	San Donato Milanese (MI)	Lombardia	Italy	20097
58	IRCCS Ospedale Casa Sollievo della Soffenza; Stru Comp di Gastroenterologia ed Endoscopia digest	San Giovanni Rotondo	Lombardia	Italy	71013
59	Ospedale Mauriziano Umberto I	Torino	Piemonte	Italy	10128
60	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana	Italy	50141
61	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana	Italy	56100
62	Azienda Ospedaliera Di Padova	Padova	Veneto	Italy	35128
63	Dong-A University Hospital	Busan		Korea, Republic of	49201
64	Pusan National University Hospital	Busan		Korea, Republic of	49241
65	Kyungpook National University Chilgok Hospital	Daegu		Korea, Republic of	41404
66	Keimyung University Dongsan Medical Center	Daegu		Korea, Republic of	41931
67	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
68	Yeungnam Univ. Hospital	Daegu		Korea, Republic of	705-717
69	Korea University Ansan Hospital	Gyeonggi-do		Korea, Republic of	15355
70	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
71	CHA Bundang Medical Centre; CHA university	Seongnam		Korea, Republic of	13520
72	Kyung Hee University Hospital	Seoul		Korea, Republic of	02447
73	Seoul National University Hospital	Seoul		Korea, Republic of	03080
74	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
75	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	03722
76	Asan Medical Center	Seoul		Korea, Republic of	05505
77	Samsung Medical Center	Seoul		Korea, Republic of	06351
78	Ajou University Hospital	Suwon City		Korea, Republic of	443-721
79	The Catholic University of Korea St. Vincent's Hospital	Suwon-si,		Korea, Republic of	442-723
80	Yonsei University Wonju Severance Christian Hospital	Wonju-Si		Korea, Republic of	220-701
81	Amsterdam UMC Location VUMC	Amsterdam		Netherlands	1081 HV
82	Amsterdam UMC Location AMC	Amsterdam		Netherlands	1105 AZ
83	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
84	Radboudumc	NL -nijmegen		Netherlands	6525 GA
85	Akershus universitetssykehus HF	Lørenskog		Norway	1478
86	Hospital de Braga	Braga		Portugal	4710-243
87	Hospital da Senhora da Oliveira Guimarães	Guimarães		Portugal	4835-044
88	Institutul Clinic Fundeni Bucuresti	Bucharest		Romania	022328
89	Spitalul Clinic Colentina	Bucharest		Romania	772202
90	S.C MedLife S.A	Bucuresti		Romania	010719
91	Centrul Medical Unirea SRL	Bucuresti		Romania	040055
92	Spitalul Clinic Judetean Mures	Targu Mures		Romania	540103
93	Centrul de Gastroenterologie Dr. Goldis	Timisoara		Romania	300002
94	Singapore General Hospital	Singapore		Singapore	169608
95	Netcare Universitas Private Hospital	Bloemfontein		South Africa	9301
96	Dr MJ Prins Practice	Cape Town		South Africa	7500
97	Dr Corne Kruger Inc.	Cape Town		South Africa	7550
98	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona	Spain	08208
99	Complejo Hospitalario Universitario de Ferrol	Ferrol	LA Coruña	Spain	15405
100	Fundacion Hospital de Alcorcon; Servicio de Digestivo	Alcorcon	Madrid	Spain	28922
101	Centro Médico Teknon	Barcelona		Spain
102	Hospital Universitario de la Princesa	Madrid		Spain	28006
103	Hospital Universitario La Paz	Madrid		Spain	280146
104	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
105	Danderyds Sjukhus AB	Stockholm		Sweden	18288
106	Inselspital-Universitaetsspital Bern	Bern		Switzerland	3010
107	Universitätsspital Zürich	Zürich		Switzerland	8091
108	The Royal Bournemouth Hospital	Bournemouth		United Kingdom	BH7 7DW
109	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
110	University Hospital Coventry	Coventry		United Kingdom	CV2 2DX
111	Royal Devon and Exeter Hospital (Wonford)	Exeter		United Kingdom	EX2 5DW
112	St James University Hospital	Leeds		United Kingdom	LS9 7TF
113	The Royal London Hospital	London		United Kingdom	E1 1FR
114	St Thomas Hospital	London		United Kingdom	SE1 7EH
115	King's College London	London		United Kingdom	SE5 9NU
116	Fairfield General Hospital	Manchester		United Kingdom	M8 5RB
117	Royal Victoria Infirmary	Newcastle upon Tyne		United Kingdom	NE1 4LP
118	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom	NG7 2UH
119	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Oct 22, 2018
• Statistical Analysis Plan - May 4, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02136069
• Other Study ID Numbers: GA29103; 2013-004282-14
• First Posted: May 12, 2014
• Last Update Posted: Dec 3, 2021
• Last Verified: Dec 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
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Infliximab; Etrolizumab

Study Results

Participant Flow

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Period Title: Overall Study
STARTED	199	198
COMPLETED	165	170
NOT COMPLETED	34	28

Baseline Characteristics

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)	Total
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.	Total of all reporting groups
Overall Participants	199	198	397
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (15.2)	39.5 (13.4)	39.8 (14.3)
Sex: Female, Male (Count of Participants)
Female	81 40.7%	66 33.3%	147 37%
Male	118 59.3%	132 66.7%	250 63%
Race/Ethnicity, Customized (Count of Participants)
Asian	39 19.6%	30 15.2%	69 17.4%
Black or African American	1 0.5%	0 0%	1 0.3%
White	150 75.4%	158 79.8%	308 77.6%
Other	9 4.5%	10 5.1%	19 4.8%
Mayo Clinic Score (MCS) ≤9 or ≥10 at Baseline (Count of Participants)
MCS ≤9	139 69.8%	147 74.2%	286 72%
MCS ≥10	60 30.2%	50 25.3%	110 27.7%
Baseline Treatment: None, Corticosteroids (CS) or Immunosuppressants (IS) Alone, or Both CS and IS (Count of Participants)
Corticosteroids (CS) Alone	59 29.6%	56 28.3%	115 29%
Immunosuppressants (IS) Alone	40 20.1%	36 18.2%	76 19.1%
Both CS and IS	25 12.6%	30 15.2%	55 13.9%
None	75 37.7%	76 38.4%	151 38%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Both Clinical Response at Week 10 and Clinical Remission at Week 54, as Determined by the Mayo Clinic Score (MCS)
Description	Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time Frame	Week 10, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	18.6 9.3%	19.7 9.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8114
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	-0.9
	Confidence Interval	() 95%; -8.70 to 6.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission at Week 10, Defined as MCS ≤2 With Individual Subscores ≤1
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease.
Time Frame	Week 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	20.6 10.4%	32.8 16.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	with margin -12.5%
Statistical Test of Hypothesis	p-Value	0.1293
	Comments	p-values are not multiplicity adjusted
	Method	Cochran-Mantel-Haenszel
	Comments	A Farrington-Manning non-inferiority test was used to determine the nominal p-value.
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	-12.0
	Confidence Interval	(2-Sided) 95%; -20.50 to -3.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission at Week 54, as Determined by the MCS
Description	Mayo Clinic Score (MCS) is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time Frame	Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	20.1 10.1%	23.7 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4056
	Comments	p-values are not multiplicity adjusted
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -11.53 to 4.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time Frame	Week 10 and Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	10.6 5.3%	13.1 6.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4591
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -8.88 to 4.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission at Week 54 Among Those With a Clinical Response at Week 10, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Time Frame	Week 10 and Week 54

Outcome Measure Data

Analysis Population Description

Participants that achieved a Clinical Response at Week 10

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	98	117
Number [percentage of participants]	37.8 19%	33.3 16.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4196
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95%; -7.54 to 18.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Time Frame	Baseline to Week 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	36.7 18.4%	49.5 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0118
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Response Rates
	Estimated Value	-12.4
	Confidence Interval	(2-Sided) 95%; -21.84 to -2.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 54, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Time Frame	Baseline to Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	27.1 13.6%	32.3 16.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2845
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Response Rates
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -13.76 to 4.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Improvement in endoscopic appearance of the mucosa is Endoscopy subscore ≤1.
Time Frame	Baseline to Week 10, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	18.1 9.1%	24.7 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1234
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Response Rates
	Estimated Value	-6.3
	Confidence Interval	(2-Sided) 95%; -14.30 to 1.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Endoscopic Remission at Week 54, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Endoscopic Remission is Endoscopy subscore = 0.
Time Frame	Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	17.6 8.8%	22.7 11.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2168
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	-5.0
	Confidence Interval	(2-Sided) 95%; -12.84 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Response at Week 10, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Time Frame	Week 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	49.2 24.7%	59.1 29.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0564
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Response Rates
	Estimated Value	-9.5
	Confidence Interval	(2-Sided) 95%; -19.06 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Response is MCS with ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.
Time Frame	Week 10, Week 54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [percentage of participants]	23.1 11.6%	29.3 14.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1729
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Response Rates
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -14.51 to 2.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Participants That Achieve Clinical Remission Corticosteroid-Free at Week 54 (Off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS
Description	MCS is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy, and physician's global assessment. Higher scores indicate more severe disease. Clinical Remission is MCS ≤2 with individual subscores ≤1.
Time Frame	Week 54

Outcome Measure Data

Analysis Population Description

Participants that were receiving corticosteroids at baseline

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	84	86
Number [percentage of participants]	15.5 7.8%	17.4 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8941
	Comments	p-value has not been adjusted for multiplicity
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference in Remission Rates
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -12.01 to 10.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants With Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
Description	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Grade 1	42 21.1%	48 24.2%
Grade 2	72 36.2%	74 37.4%
Grade 3	35 17.6%	23 11.6%
Grade 4	5 2.5%	5 2.5%
Grade 5	0 0%	1 0.5%

14. Secondary Outcome

Title	Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [participants]	29 14.6%	25 12.6%

15. Secondary Outcome

Title	Number of Participants With Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0
Description	All AEs were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Grade 1	28 14.1%	27 13.6%
Grade 2	31 15.6%	29 14.6%
Grade 3	8 4%	4 2%
Grade 4	2 1%	1 0.5%
Grade 5	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With Serious Infection-Related Adverse Events
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [participants]	11 5.5%	3 1.5%

17. Secondary Outcome

Title	Number of Participants With Malignancies
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Number [participants]	3 1.5%	1 0.5%

18. Secondary Outcome

Title	Number of Participants With Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0
Description	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Grade 1	7 3.5%	5 2.5%
Grade 2	0 0%	2 1%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0
Description	All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time Frame	Baseline until the end of study (up to 66 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	199	198
Grade 1	0 0%	2 1%
Grade 2	0 0%	7 3.5%
Grade 3	0 0%	1 0.5%
Grade 4	0 0%	2 1%
Grade 5	0 0%	0 0%

20. Secondary Outcome

Title	Pharmacokinetics: Etrolizumab Serum Concentration
Time Frame	Weeks 2, 10, 12, 30, and 54

Outcome Measure Data

Analysis Population Description

A subset of etrolizumab-treated participants who received at least one dose of study drug and had at least one quantifiable concentration measured post baseline.

Arm/Group Title	Etrolizumab + Placebo (IV)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
Measure Participants	153
Week 2	7.64 (2.75)
Week 10	12.0 (4.63)
Week 12	6.92 (3.18)
Week 32	13.9 (5.96)
Week 54	13.2 (5.68)

21. Secondary Outcome

Title	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54
Description	The IBDQ is used to assess participant's health-related quality of life (QOL). The 32-item questionnaire contains four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). The items are scored on a 7-point Likert scale with a higher score indicating better health-related QOL. IBDQ score is a total score summed up from across all 32 questions on the questionnaire. The score can range from 32-224 and the higher score indicates a better quality of life.
Time Frame	Weeks 10, 30, and 54

Outcome Measure Data

Analysis Population Description

Participants that completed the IBDQ Questionnaire at baseline and at the respective Time Points

Arm/Group Title	Etrolizumab + Placebo (IV)	Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.	Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
Measure Participants	165	156
Week 10	43.2 (36.6)	45.1 (39.4)
Week 30	53.5 (40.8)	59.6 (34.4)
Week 54	58.2 (32.9)	63.2 (38.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments	Week 10
Statistical Test of Hypothesis	p-Value	0.4106
	Comments	p-value has not been adjusted for multiplicity
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -10.6 to 4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments	Week 30
Statistical Test of Hypothesis	p-Value	0.1434
	Comments	p-value has not been adjusted for multiplicity
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-5.7
	Confidence Interval	(2-Sided) 95%; -13.3 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etrolizumab + Placebo (IV), Infliximab + Placebo (Injection)
	Comments
	Type of Statistical Test	Superiority
	Comments	Week 54
Statistical Test of Hypothesis	p-Value	0.1103
	Comments	p-value has not been adjusted for multiplicity
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -13.6 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
Time Frame	Weeks 0, 4, 10, 12, 30, and 54

Outcome Measure Data

Analysis Population Description

A subset of etrolizumab-treated participants with at least one baseline or post-baseline ATA result from at least one sample.

Arm/Group Title	Etrolizumab + Placebo (IV)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
Measure Participants	196
Number [participants]	69 34.7%

Adverse Events

Time Frame	Baseline until the end of study (up to 66 weeks)
Arm/Group Title	Etrolizumab + Placebo (IV)		Infliximab + Placebo (Injection)
Arm/Group Description	Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.		Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.
All Cause Mortality
	Etrolizumab + Placebo (IV)		Infliximab + Placebo (Injection)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/199 (0%)		1/198 (0.5%)
Serious Adverse Events
	Etrolizumab + Placebo (IV)		Infliximab + Placebo (Injection)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/199 (16.1%)		20/198 (10.1%)
Blood and lymphatic system disorders
Anaemia	1/199 (0.5%)	1	0/198 (0%)	0
Eye disorders
Retinal vein occlusion	0/199 (0%)	0	1/198 (0.5%)	1
Gastrointestinal disorders
Abdominal pain	2/199 (1%)	2	0/198 (0%)	0
Colitis ulcerative	12/199 (6%)	12	11/198 (5.6%)	11
Incarcerated umbilical hernia	0/199 (0%)	0	1/198 (0.5%)	1
Pancreatitis acute	0/199 (0%)	0	1/198 (0.5%)	1
Small intestinal obstruction	0/199 (0%)	0	1/198 (0.5%)	1
Immune system disorders
Anaphylactic reaction	0/199 (0%)	0	1/198 (0.5%)	1
Drug hypersensitivity	0/199 (0%)	0	1/198 (0.5%)	1
Hypersensitivity	0/199 (0%)	0	1/198 (0.5%)	1
Infections and infestations
Anal abscess	3/199 (1.5%)	3	0/198 (0%)	0
Appendicitis	2/199 (1%)	2	0/198 (0%)	0
Bacteraemia	1/199 (0.5%)	1	0/198 (0%)	0
Cytomegalovirus colitis	1/199 (0.5%)	1	1/198 (0.5%)	1
Lower respiratory tract infection	0/199 (0%)	0	1/198 (0.5%)	1
Meningitis listeria	0/199 (0%)	0	1/198 (0.5%)	1
Orchitis	1/199 (0.5%)	1	0/198 (0%)	0
Pneumonia	1/199 (0.5%)	1	0/198 (0%)	0
Pyelonephritis	1/199 (0.5%)	1	0/198 (0%)	0
Sepsis	1/199 (0.5%)	1	0/198 (0%)	0
Stitch abscess	1/199 (0.5%)	1	0/198 (0%)	0
Viral upper respiratory tract infection	1/199 (0.5%)	1	0/198 (0%)	0
Injury, poisoning and procedural complications
Incisional hernia	1/199 (0.5%)	2	0/198 (0%)	0
Procedural intestinal perforation	1/199 (0.5%)	1	0/198 (0%)	0
Tendon rupture	1/199 (0.5%)	1	0/198 (0%)	0
Thoracic vertebral fracture	1/199 (0.5%)	1	0/198 (0%)	0
Investigations
Haemoglobin decreased	1/199 (0.5%)	1	0/198 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/199 (0.5%)	1	0/198 (0%)	0
Hodgkin's disease	1/199 (0.5%)	1	0/198 (0%)	0
Neuroendocrine tumour	0/199 (0%)	0	1/198 (0.5%)	1
Nervous system disorders
Central nervous system vasculitis	1/199 (0.5%)	1	0/198 (0%)	0
Renal and urinary disorders
Haematuria	1/199 (0.5%)	1	0/198 (0%)	0
Renal colic	2/199 (1%)	2	0/198 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/199 (0%)	0	1/198 (0.5%)	1
Skin and subcutaneous tissue disorders
Erythema	0/199 (0%)	0	1/198 (0.5%)	1
Pyoderma gangrenosum	1/199 (0.5%)	1	0/198 (0%)	0
Other (Not Including Serious) Adverse Events
	Etrolizumab + Placebo (IV)		Infliximab + Placebo (Injection)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/199 (47.2%)		80/198 (40.4%)
Gastrointestinal disorders
Abdominal pain	10/199 (5%)	11	5/198 (2.5%)	6
Colitis ulcerative	45/199 (22.6%)	47	33/198 (16.7%)	36
Diarrhoea	11/199 (5.5%)	12	4/198 (2%)	4
Nausea	10/199 (5%)	10	4/198 (2%)	4
Infections and infestations
Nasopharyngitis	22/199 (11.1%)	30	23/198 (11.6%)	30
Musculoskeletal and connective tissue disorders
Arthralgia	21/199 (10.6%)	24	15/198 (7.6%)	16
Nervous system disorders
Headache	22/199 (11.1%)	30	19/198 (9.6%)	28

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.