BI 695501 Versus Humira in Patients With Active Crohn's Disease: a Trial Comparing Efficacy, Endoscopic Improvement, Safety, and Immunogenicity

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02871635
• Collaborator: (none)
• Enrollment: 147
• Locations: 92
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

The primary objective of this trial is to compare the clinical efficacy of BI 695501 with EU-approved Humira® in patients with active Crohn's disease (CD).

Secondary Objectives:

The secondary objectives of this trial are to compare the efficacy and safety of BI 695501 with EU-approved Humira® across the induction and maintenance phases.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Drug: BI 695501; Drug: HUMIRA	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 147 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: BI 695501 Versus Humira® in Patients With Active Crohn's Disease: a Randomized, Double-blind, Multicenter, Parallel Group, Exploratory Trial Comparing Efficacy, Endoscopic Improvement, Safety, and Immunogenicity
• Actual Study Start Date: Sep 28, 2016
• Actual Primary Completion Date: Apr 30, 2019
• Actual Study Completion Date: May 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 695501	Drug: BI 695501
Active Comparator: HUMIRA + BI 695501	Drug: BI 695501; Drug: HUMIRA

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With a Clinical Response (CDAI Decrease of ≥70 Compared With Baseline) at Week 4 [Week 4]

   The Crohn's Disease Activity Index (CDAI) is a validated instrument to measure disease severity in Crohn's Disease (CD). The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. The CDAI decrease at Week 4 was assessed as the decrease relative to baseline measurement, patients with a decrease ≥70 were responders. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to non-responder imputation (NRI) and last observation carried forward (LOCF).

Secondary Outcome Measures

1. Percentage of Patients With a Clinical Response (CDAI Decrease of ≥70 Compared With Baseline) at Week 24 [Week 24]

   The CDAI is a validated instrument to measure disease severity in CD. The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. The CDAI decrease at Week 24 was assessed as the decrease relative to baseline measurement, patients with a decrease ≥70 were responders. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to NRI and LOCF.

2. Percentage of Patients in Clinical Remission (CDAI <150) at Week 24 [at Week 24]

   The CDAI is a validated instrument to measure disease severity in CD. The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. Patients with CDAI <150 at Week 24 were considered as clinical remission cases. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to NRI and LOCF.

3. Percentage of Patients With Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESIs) [From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.]

   Analysis of AEs focused on treatment-emergent AEs (TEAEs). For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46. TEAEs and SAEs (including investigator-assessed trial medication-related TEAEs) and AESIs are reported. The following were considered an AESI: hepatic injury, anaphylactic reactions, serious infection and hypersensitivity reactions.

4. Percentage of Patients With Infections [From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.]

   The percentage of patients with TEAEs for infections are reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.

5. Percentage of Patients With Serious Infections [From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.]

   The percentage of patients with TEAEs for serious infections are reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.

6. Percentage of Patients Who Experienced Hypersensitivity Reactions [From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.]

   The percentage of patients with TEAEs for hypersensitivity reactions is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.

7. Percentage of Patients Who Experienced Drug Induced Liver Injury (DILI) [From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.]

   The percentage of patients with TEAEs for DILIs is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.

8. Percentage of Patients With Injection Site Reactions [From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.]

   The percentage of patients with TEAEs for injection site reactions is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Males and females aged >=18 and =<80 years at Screening who have a diagnosis of moderate to severely active Crohn's Disease (CD), confirmed by endoscopy or radiologic evaluation, for more than 4 months with evidence of mucosal ulceration. Patients must have all of the following:

• Crohn's Disease Activity Index (CDAI) score of >=220 and =<450

• A diagnosis of Crohn's Disease (CD) confirmed by ileocolonoscopy during Screening

• Presence of mucosal ulcers in at least one segment of the ileum or colon and a SES-CD score ≥7 (for patients with isolated ileal disease SES-CD score ≥4), as assessed by ileocolonoscopy and confirmed by central independent reviewer(s) before randomization

• Anti-tumor necrosis factor (TNF) patients or patients previously treated with infliximab who had initially responded and who meet one of the following criteria:

• Responded and developed secondary resistance due confirmed anti-infliximab anti-drug antibody formation, which caused infliximab depletion

• Responded and became intolerant

• Further inclusion criteria apply

Exclusion criteria:

• Patients with ulcerative colitis or indeterminate colitis

• Patients with symptomatic known obstructive strictures

• Surgical bowel resection performed within 6 months prior to Screening or planned resection at any time while enrolled in the trial

• Patients with an ostomy or ileoanal pouch

• Patients with short bowel syndrome

• Patients who have previously used infliximab and have never clinically responded

• Patients who have previously received treatment with adalimumab, or who have participated in an adalimumab or adalimumab biosimilar clinical trial

• Further exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Borland-Groover Clinic	Jacksonville	Florida	United States	32256
2	Hope Clinical Research	Kissimmee	Florida	United States	34741
3	Center for Advanced GI	Maitland	Florida	United States	32751
4	Advance Medical Research Center	Miami	Florida	United States	33155
5	Advanced Research Institute, Inc	New Port Richey	Florida	United States	34653
6	Doctors Clinical Research	East Point	Georgia	United States	30344
7	Southwest Gastroenterology	Oak Lawn	Illinois	United States	60453
8	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7702
9	MGG Group Co. Inc. / Chevy Chase Clinical Research,	Chevy Chase	Maryland	United States	20815
10	Gastro Center of Maryland	Columbia	Maryland	United States	21045
11	Healthcare Research Network	Hazelwood	Missouri	United States	63042
12	Asheville Gastroenterology Associates, PA	Asheville	North Carolina	United States	28801
13	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio	United States	44060
14	Gastroenterology Associates, PA	Greenville	South Carolina	United States	29615
15	Houston Endoscopy and Research Center	Houston	Texas	United States	77079
16	Biopharma Informatic, Inc, dba Research Consultants	Katy	Texas	United States	77450
17	Sagact, Pllc	San Antonio	Texas	United States	78229
18	Baylor Scott and White Healthcare	Temple	Texas	United States	76508
19	Victoria Gastroenterology	Victoria	Texas	United States	77904
20	Gomel Regional Clinical	Gomel		Belarus	246012
21	City Clinical Hospital # 10	Minsk		Belarus	220096
22	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk		Belarus	210603
23	University Clinical Centre Sarajevo	Sarajevo		Bosnia and Herzegovina	71000
24	Clinical Hospital Osijek	Osijek		Croatia	31000
25	Polyclinic Bonifarm	Zagreb		Croatia	10000
26	Vojenska nemocnice Brno	Brno		Czechia	63600
27	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove		Czechia	50012
28	CTCenter Mave, s.r.o., Cllinical Trials Center, Olomouc	Olomouc		Czechia	779 00
29	Gregar s.r.o.	Olomouc		Czechia	779 00
30	PreventaMed, s.r.o.	Olomouc		Czechia	77900
31	University Hospital Ostrava	Ostrava-Poruba		Czechia	708 52
32	Vitkovice Hospital	Ostrava-Vitkovice		Czechia	703 84
33	Medicon, a.s.	Prague		Czechia	140 00
34	University Hospital Na Bulovce	Praha 8		Czechia	27711
35	Axon Clinical, s.r.o.	Praha		Czechia	15000
36	General Hospital Pribram	Pribram		Czechia	261 01
37	Masaryk Hospital, Internal Department	Usti nad Labem		Czechia	401 13
38	Crohn Colitis Centrum Rhein Main	Frankfurt		Germany	60594
39	General Hospital of Athens Evangelismos	Athens		Greece	10676
40	University General Hospital of Heraklion	Heraklion, Crete		Greece	71110
41	General Hospital of Rhodes	Rhodes		Greece	85100
42	Haemek Medical Center	Afula		Israel	18101
43	Wolfson Medical Center	Holon		Israel	58100
44	Hadassah Medical Center, Ein-Karem	Jerusalem		Israel	9112001
45	Meir Medical Center	Kfar-Saba		Israel	4428164
46	The Chaim Sheba Medical Center Tel Hashomer	Ramat Gan		Israel	52621
47	Kaplan Medical Center	Rehovot		Israel	76100
48	KLIMED Marek Klimkiewicz	Bialystok		Poland	15-765
49	NZOZ Centrum Medyczne KERmed	Bydgoszcz		Poland	85231
50	Medical Center Pleiades	Cracow		Poland	30-363
51	Polimedica Centrum Badan	Kielce		Poland	25634
52	Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla	Knurow		Poland	44190
53	SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia	Lodz		Poland	90-302
54	Clinic Medical Center; Nowa Sol	Nowa Sol		Poland	67-100
55	Ai Medical Center, private practice, Poznan	Poznan		Poland	61-113
56	Gabinet Lekarski Bartosz Korczowski	Rzeszow		Poland	35302
57	Specialized Medical Practice. Dr med. Marek Horynski	Sopot		Poland	81756
58	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin		Poland	71270
59	Multidisciplinary Medical Clinic "Anthurium"	Barnaul		Russian Federation	656043
60	GUZ Reg. Clinical Hospital, Kemerovo	Kemerovo		Russian Federation	650066
61	Clinical Hospital No. 24, Moscow	Moscow		Russian Federation	127015
62	Murmansk Regional Clinical Hospital named after Bayandin	Murmansk		Russian Federation	183047
63	Reg.Clin.Hosp.n.a.Semashko	Nizhniy Novgorod		Russian Federation	603126
64	State Novosibirsk Regional Clinical Hospital	Novosibirsk		Russian Federation	630091
65	FSBSI "Scientific and Research Institute of Physiology and Basic Medicine"	Novosibirsk		Russian Federation	630117
66	BHI of Omsk region - Clinical Oncology Dispensary	Omsk		Russian Federation	644013
67	SBIH City Clinical Hospital #31	Saint Petersburg		Russian Federation	194291
68	LLC IClinic	Saint Petersburg		Russian Federation	197110
69	Private Educational Institution of Higher Education "Medical University "REAVIZ"	Samara		Russian Federation	443001
70	NonState Healthcare Institution Central Clinical Hospital, Samara station JSC "Russian Railways"	Samara		Russian Federation	443041
71	Baltic Med,LLC Clinic BaltMed Ozerki	St. Petersburg		Russian Federation	194356
72	EKO-Bezopasnost, St. Petersburg	St. Petersburg		Russian Federation	196143
73	Clinical Medical Center Zvezdara, Belgrade	Belgrade		Serbia	11000
74	Military Medical Academy	Belgrade		Serbia	11000
75	Clinical Center Bezanijska kosa, Belgrade	Belgrade		Serbia	11080
76	Clinical Center Zemun	Belgrade		Serbia	11080
77	Clinical Center Kragujevac	Kragujevac		Serbia	34000
78	Gazi University Medical Faculty	Ankara		Turkey	06500
79	Gaziantep University Medical Faculty Sahinbey Educational Research Hospital	Gaziantep		Turkey	27310
80	Kartal Lutfi Kirdar Research and Training Hospital	Istanbul		Turkey	34890
81	Kocaeli University Research and Training Hospital	Kocaeli		Turkey	41380
82	CI Cherkasy RH of Cherkasy Reg.Council	Cherkasy		Ukraine	18009
83	CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2	Kharkiv		Ukraine	61037
84	Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC	Kiev		Ukraine	02091
85	Private Enterprise Private Manufacturing Company "Acinus"	Kirovohrad		Ukraine	25006
86	Medical Center Medical Clinic Kyiv	Kyiv		Ukraine	01601
87	Clin Hosp.8 P.L.Shupyk NMA of PGE	Kyiv		Ukraine	04201
88	Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3	Vinnytsia		Ukraine	21005
89	M.I. Pyrogov VRCH, Vinnytsia	Vinnytsia		Ukraine	21018
90	Clin.Hosp#1,Zaporizhzhia	Zaporizhzhia		Ukraine	69104
91	Royal Bournemouth and Christchurch Hospital	Bournemouth		United Kingdom	BH7 7DW
92	Walsall Manor Hospital	Walsall		United Kingdom	WS2 9PS

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Dec 12, 2017
• Statistical Analysis Plan - May 22, 2019

More Information

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02871635
• Other Study ID Numbers: 1297.4; 2016-000612-14
• First Posted: Aug 18, 2016
• Last Update Posted: Jun 4, 2020
• Last Verified: May 1, 2020

• Additional relevant MeSH terms: Crohn Disease; Adalimumab

Study Results

Participant Flow

Recruitment Details	This was an exploratory, randomized, 56-week, double-blind, parallel arm, multiple dose, active comparator trial of BI 695501 and EU-approved Humira, with a 48-week treatment period and a 10-week follow-up period (starting after last dose of trial medication at Week 46) in patients with moderately to severely active Crohn's Disease (CD)
Pre-assignment Detail	The trial consisted of a screening period of up to a maximum of 28 days, a 48-week treatment period consisting of an induction period from baseline to Week 4 and a maintenance period from Week 5 to Week 48, and a 10-week safety follow-up period (starting after last dose of trial medication at Week 46).

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Period Title: Overall Study
STARTED	72	75
COMPLETED	54	56
NOT COMPLETED	18	19

Baseline Characteristics

Arm/Group Title	BI 695501	Humira EU	Total
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.	Total of all reporting groups
Overall Participants	72	75	147
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (13.44)	33.2 (11.52)	35.3 (12.63)
Sex: Female, Male (Count of Participants)
Female	33 45.8%	31 41.3%	64 43.5%
Male	39 54.2%	44 58.7%	83 56.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.4%	0 0%	1 0.7%
Not Hispanic or Latino	69 95.8%	67 89.3%	136 92.5%
Unknown or Not Reported	2 2.8%	8 10.7%	10 6.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.4%	0 0%	1 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.4%	1 1.3%	2 1.4%
White	69 95.8%	74 98.7%	143 97.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.4%	0 0%	1 0.7%
Crohn's Disease Activity Index score at baseline (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	307.3 (76.69)	303.6 (64.39)	305.4 (70.46)

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With a Clinical Response (CDAI Decrease of ≥70 Compared With Baseline) at Week 4
Description	The Crohn's Disease Activity Index (CDAI) is a validated instrument to measure disease severity in Crohn's Disease (CD). The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. The CDAI decrease at Week 4 was assessed as the decrease relative to baseline measurement, patients with a decrease ≥70 were responders. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to non-responder imputation (NRI) and last observation carried forward (LOCF).
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) contained all randomized patients who received at least 1 dose of trial medication, and had all efficacy measures relevant for the CDAI, measured at baseline and at least once postbaseline.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	68	72
Number [Percentage of participants]	88.0 122.2%	93.1 124.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, Humira EU
	Comments	Was analyzed using a log-linked binomial model, described as: response to treatment at Week 4 = treatment+prior infliximab exposure+screening Simple Endoscopic Score for Crohn's Disease (SES-CD)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.945
	Confidence Interval	(2-Sided) 90%; 0.870 to 1.028
	Parameter Dispersion	Type: Value:
	Estimation Comments	BI 695501 as numerator Humira EU as denominator

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 695501, Humira EU
	Comments	Was to be analyzed using a log-linked binomial model, described as: response to treatment at Week 4 = treatment+prior infliximab exposure+screening Simple Endoscopic Score for Crohn's Disease (SES-CD)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.945
	Confidence Interval	(2-Sided) 95%; 0.856 to 1.044
	Parameter Dispersion	Type: Value:
	Estimation Comments	BI 695501 as numerator Humira EU as denominator

2. Secondary Outcome

Title	Percentage of Patients With a Clinical Response (CDAI Decrease of ≥70 Compared With Baseline) at Week 24
Description	The CDAI is a validated instrument to measure disease severity in CD. The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. The CDAI decrease at Week 24 was assessed as the decrease relative to baseline measurement, patients with a decrease ≥70 were responders. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to NRI and LOCF.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The FAS contained all randomized patients who received at least 1 dose of trial medication, and had all efficacy measures relevant for the CDAI, measured at baseline and at least once postbaseline.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	68	72
Number [Percentage of participants]	87.4 121.4%	87.4 116.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, Humira EU
	Comments	Was to be analyzed using a log-linked binomial model, described as: response to treatment at Week 24 = treatment+prior infliximab exposure+screening Simple Endoscopic Score for Crohn's Disease (SES-CD)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.000
	Confidence Interval	(2-Sided) 90%; 0.871 to 1.148
	Parameter Dispersion	Type: Value:
	Estimation Comments	BI 695501 as numerator Humira EU as denominator

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 695501, Humira EU
	Comments	Was to be analyzed using a log-linked binomial model, described as: response to treatment at Week 24 = treatment+prior infliximab exposure+screening Simple Endoscopic Score for Crohn's Disease (SES-CD)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.000
	Confidence Interval	(2-Sided) 95%; 0.848 to 1.178
	Parameter Dispersion	Type: Value:
	Estimation Comments	BI 695501 as numerator Humira EU as denominator

3. Secondary Outcome

Title	Percentage of Patients in Clinical Remission (CDAI <150) at Week 24
Description	The CDAI is a validated instrument to measure disease severity in CD. The CDAI score is a sum of the 8 factors (number of liquid stools, abdominal pain, general well-being, extra-intestinal complications, antidiarrheal drugs, abdominal mass, hematocrit and body weight) after adjustment with a weighting factor. Higher CDAI scores indicating more active disease. Patients with CDAI <150 at Week 24 were considered as clinical remission cases. Percentage=least squares means per treatment group back transformed using inverse logit function. Missing data were imputed according to NRI and LOCF.
Time Frame	at Week 24

Outcome Measure Data

Analysis Population Description

The FAS contained all randomized patients who received at least 1 dose of trial medication, and had all efficacy measures relevant for the CDAI, measured at baseline and at least once postbaseline.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	68	72
Number [Percentage of participants]	68.6 95.3%	76.2 101.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 695501, Humira EU
	Comments	Was to be analyzed using a log-linked binomial model, described as: response to treatment at Week 24 = treatment+prior infliximab exposure+screening Simple Endoscopic Score for Crohn's Disease (SES-CD)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.900
	Confidence Interval	(2-Sided) 90%; 0.751 to 1.078
	Parameter Dispersion	Type: Value:
	Estimation Comments	BI 695501 as numerator Humira EU as denominator

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 695501, Humira EU
	Comments	Was to be analyzed using a log-linked binomial model, described as: response to treatment at Week 24 = treatment+prior infliximab exposure+screening Simple Endoscopic Score for Crohn's Disease (SES-CD)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.9000
	Confidence Interval	(2-Sided) 95%; 0.725 to 1.116
	Parameter Dispersion	Type: Value:
	Estimation Comments	BI 695501 as numerator Humira EU as denominator

4. Secondary Outcome

Title	Percentage of Patients With Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESIs)
Description	Analysis of AEs focused on treatment-emergent AEs (TEAEs). For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46. TEAEs and SAEs (including investigator-assessed trial medication-related TEAEs) and AESIs are reported. The following were considered an AESI: hepatic injury, anaphylactic reactions, serious infection and hypersensitivity reactions.
Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (SAF) contained all randomized patients who received at least 1 dose (full or partial) of trial medication.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	72	75
TEAE -Period 1	62.5 86.8%	56.0 74.7%
serious TEAE - Period 1	8.3 11.5%	10.7 14.3%
AESI TEAE - Period 1	2.8 3.9%	2.7 3.6%
TEAE - Period 2	43.1 59.9%	45.3 60.4%
serious TEAE - Period 2	2.8 3.9%	12.0 16%
AESI TEAE - Period 2	2.8 3.9%	2.7 3.6%

5. Secondary Outcome

Title	Percentage of Patients With Infections
Description	The percentage of patients with TEAEs for infections are reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.
Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Outcome Measure Data

Analysis Population Description

The SAF contained all randomized patients who received at least 1 dose (full or partial) of trial medication.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	72	75
Period 1	23.6 32.8%	22.7 30.3%
Period 2	19.4 26.9%	22.7 30.3%

6. Secondary Outcome

Title	Percentage of Patients With Serious Infections
Description	The percentage of patients with TEAEs for serious infections are reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.
Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Outcome Measure Data

Analysis Population Description

The SAF contained all randomized patients who received at least 1 dose (full or partial) of trial medication.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	72	75
Period 1	2.8 3.9%	2.7 3.6%
Period 2	1.4 1.9%	4.0 5.3%

7. Secondary Outcome

Title	Percentage of Patients Who Experienced Hypersensitivity Reactions
Description	The percentage of patients with TEAEs for hypersensitivity reactions is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.
Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Outcome Measure Data

Analysis Population Description

The SAF contained all randomized patients who received at least 1 dose (full or partial) of trial medication.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	72	75
Period 1	5.6 7.8%	2.7 3.6%
Period 2	2.8 3.9%	6.7 8.9%

8. Secondary Outcome

Title	Percentage of Patients Who Experienced Drug Induced Liver Injury (DILI)
Description	The percentage of patients with TEAEs for DILIs is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.
Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Outcome Measure Data

Analysis Population Description

The SAF contained all randomized patients who received at least 1 dose (full or partial) of trial medication.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	72	75
Period 1	0.0 0%	0.0 0%
Period 2	0.0 0%	0.0 0%

9. Secondary Outcome

Title	Percentage of Patients With Injection Site Reactions
Description	The percentage of patients with TEAEs for injection site reactions is reported. For the period 1 'Baseline - Week 24', TEAEs were defined as AEs that started or worsened on or after first dose of trial medication and prior to date of the Week 24 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients who discontinued treatment before Week 24. For the period 2 'Week 24 - Week 46', TEAEs were defined as AEs that started or worsened on Week 24 visit and prior to or on Week 56 visit or within 10 weeks (70 days, inclusive) after last dose of trial medication for patients discontinuing treatment prior to Week 46.
Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.

Outcome Measure Data

Analysis Population Description

The SAF contained all randomized patients who received at least 1 dose (full or partial) of trial medication.

Arm/Group Title	BI 695501	Humira EU
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (Crohn's Disease Activity Index (CDAI) decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.	Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
Measure Participants	72	75
Period 1	0.0 0%	6.7 8.9%
Period 2	1.4 1.9%	1.3 1.7%

Adverse Events

Time Frame	From first administration of trial medication until 10 weeks after last administration, up to a maximum of 56 weeks.
Adverse Event Reporting Description	The Safety Analysis Set (SAF) contained all randomized patients who received at least 1 dose (full or partial) of trial medication.
Arm/Group Title	BI 695501 (Baseline - Week 24 + 10 Weeks [70 Days])		Humira (Baseline - Week 24 + 10 Weeks [70 Days])		BI 695501 (Week 24 - Week 46 + 10 Weeks [70 Days])		Humira (Week 24 - Week 46 + 10 Weeks [70 Days])
Arm/Group Description	Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (CDAI decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.		Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.		Patients randomized to BI 695501 received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders (CDAI decrease of ≥70 compared to baseline), patients continued to receive BI 695501 every 2 weeks until the end of the treatment (EoT) period (Week 46). Patients were administered with a loading dose of 160 milligram (mg) BI 695501 on Day 1, followed by 80 mg BI 695501 2 weeks later (Day 15), and thereafter 40 mg BI 695501 every 2 weeks until Week 46. Trial medication was administered by subcutaneous (SC) injection.		Patients randomized to EU-approved Humira received treatment every 2 weeks until Week 4 when they were assessed for clinical response. If classified as responders, patients continued to receive EU-approved Humira until Week 22 and then switched to receive BI 695501 every 2 weeks from Week 24 until the EoT period (Week 46). Patients were administered with a loading dose of 160 mg EU-approved Humira on Day 1, followed by 80 mg EU-approved Humira 2 weeks later (Day 15), and 40 mg EU-approved Humira every 2 weeks until Week 22. Patients were then switched to receive 40 mg BI 695501 every 2 weeks from Week 24 until Week 46. Trial medication was administered by SC injection.
All Cause Mortality
	BI 695501 (Baseline - Week 24 + 10 Weeks [70 Days])		Humira (Baseline - Week 24 + 10 Weeks [70 Days])		BI 695501 (Week 24 - Week 46 + 10 Weeks [70 Days])		Humira (Week 24 - Week 46 + 10 Weeks [70 Days])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/72 (0%)		0/75 (0%)		0/72 (0%)		0/75 (0%)
Serious Adverse Events
	BI 695501 (Baseline - Week 24 + 10 Weeks [70 Days])		Humira (Baseline - Week 24 + 10 Weeks [70 Days])		BI 695501 (Week 24 - Week 46 + 10 Weeks [70 Days])		Humira (Week 24 - Week 46 + 10 Weeks [70 Days])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/72 (8.3%)		8/75 (10.7%)		2/72 (2.8%)		9/75 (12%)
Gastrointestinal disorders
Crohn's disease	2/72 (2.8%)		5/75 (6.7%)		1/72 (1.4%)		1/75 (1.3%)
Anal fistula	1/72 (1.4%)		1/75 (1.3%)		0/72 (0%)		0/75 (0%)
Large intestinal haemorrhage	0/72 (0%)		1/75 (1.3%)		0/72 (0%)		0/75 (0%)
Small intestinal obstruction	0/72 (0%)		1/75 (1.3%)		0/72 (0%)		0/75 (0%)
Dyspepsia	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Pancreatitis chronic	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
General disorders
Non-cardiac chest pain	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Infections and infestations
Acute sinusitis	1/72 (1.4%)		0/75 (0%)		0/72 (0%)		0/75 (0%)
Anal abscess	0/72 (0%)		1/75 (1.3%)		0/72 (0%)		0/75 (0%)
Postoperative wound infection	0/72 (0%)		1/75 (1.3%)		0/72 (0%)		0/75 (0%)
Pulmonary tuberculosis	1/72 (1.4%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Psoas abscess	0/72 (0%)		0/75 (0%)		1/72 (1.4%)		0/75 (0%)
Rotavirus infection	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Upper respiratory tract infection	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Injury, poisoning and procedural complications
Joint injury	1/72 (1.4%)		0/75 (0%)		0/72 (0%)		0/75 (0%)
Musculoskeletal and connective tissue disorders
Joint swelling	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Musculoskeletal pain	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Nervous system disorders
Multiple sclerosis	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Pregnancy, puerperium and perinatal conditions
Ruptured ectopic pregnancy	0/72 (0%)		1/75 (1.3%)		0/72 (0%)		0/75 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Palmoplantar pustulosis	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Pruritus	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Pyoderma gangrenosum	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Rash erythematous	0/72 (0%)		0/75 (0%)		0/72 (0%)		1/75 (1.3%)
Other (Not Including Serious) Adverse Events
	BI 695501 (Baseline - Week 24 + 10 Weeks [70 Days])		Humira (Baseline - Week 24 + 10 Weeks [70 Days])		BI 695501 (Week 24 - Week 46 + 10 Weeks [70 Days])		Humira (Week 24 - Week 46 + 10 Weeks [70 Days])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/72 (31.9%)		16/75 (21.3%)		13/72 (18.1%)		12/75 (16%)
Gastrointestinal disorders
Crohn's disease	4/72 (5.6%)		3/75 (4%)		0/72 (0%)		2/75 (2.7%)
Abdominal pain	3/72 (4.2%)		2/75 (2.7%)		1/72 (1.4%)		5/75 (6.7%)
Infections and infestations
Respiratory tract infection	5/72 (6.9%)		3/75 (4%)		0/72 (0%)		3/75 (4%)
Upper respiratory tract infection	3/72 (4.2%)		5/75 (6.7%)		2/72 (2.8%)		1/75 (1.3%)
Nasopharyngitis	2/72 (2.8%)		2/75 (2.7%)		5/72 (6.9%)		3/75 (4%)
Investigations
Weight increased	4/72 (5.6%)		1/75 (1.3%)		3/72 (4.2%)		0/75 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/72 (8.3%)		0/75 (0%)		2/72 (2.8%)		0/75 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.