Study to Evaluate Efficacy and Safety of Two Drug Regimens in Subjects With Moderate to Severe Crohn's Disease

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02065570
• Collaborator: (none)
• Enrollment: 514
• Locations: 143
• Arms: 4
• Actual Duration (Months): 69
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate higher versus standard adalimumab dosing regimens for induction and maintenance therapy in subjects with moderately to severely active Crohn's Disease and evidence of mucosal ulceration.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Drug: Adalimumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 514 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind Study to Evaluate Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease and Evidence of Mucosal Ulceration
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jan 30, 2020
• Actual Study Completion Date: Jan 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Induction: Standard Induction Dose Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.	Drug: Adalimumab; Other Names: Humira ; Drug: Placebo
Experimental: Induction: Higher Induction Dose Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.	Drug: Adalimumab; Other Names: Humira
Experimental: Maintenance: Clinically Adjusted (CA) Regimen Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.	Drug: Adalimumab; Other Names: Humira
Experimental: Maintenance: Therapeutic Drug Monitoring (TDM) Regimen At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM will be determined by protocol-established dose adjustment criteria. Doses will be determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 will receive 40 mg ew.	Drug: Adalimumab; Other Names: Humira

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Clinical Remission at Week 4 [Week 4]

   Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.

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

   Endoscopic response was scored using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score > 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline) at Week 12.

3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).]

   Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. Serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. TEAEs: any event that began or worsened in severity after the first dose of study drug in the induction or maintenance study. Events with unknown severity were counted as severe. Events with unknown relationship to study drug were counted as drug-related.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12 [Week 4 and Week 12]

   CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.

2. Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12 [Week 12]

   Clinical response was scored using CDAI, which assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline. Endoscopic response was scored using the SES-CD, which evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score >50% from Baseline (or for Baseline SES-CD of 4, at least a 2-point reduction from Baseline) at Week 12.

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

   Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.

4. Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline [Week 12]

   Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.

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

   Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.

6. Change From Baseline in Fecal Calprotectin Level at Week 4 [Baseline, Week 4]

7. Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4 [Week 4]

8. Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4 [Week 4]

   Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.

9. Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g and Endoscopic Remission at Week 12 [Week 12]

   Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.

10. Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12 [Week 12]

    The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease.

11. Percentage of Participants With Clinical Response at Week 4 [Week 4]

    Clinical response was scored using CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from baseline.

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

    Clinical response was scored using CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline.

13. Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4 [Week 4]

    The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8.

14. Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12 [Week 12]

    The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8.

15. Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12 [Week 12]

    The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Crohn's disease (CD) for at least 90 days, confirmed by endoscopy during the Screening Period.

• Active CD with a Crohn's Disease Activity Index (CDAI) despite treatment with oral corticosteroids and/or immunosuppressants.

• Mucosal ulceration on endoscopy.

Exclusion Criteria:

• Subject with ulcerative colitis or indeterminate colitis.

• Subject who has had surgical bowel resections in the past 6 months or is planning resection.

• Subjects with an ostomy or ileoanal pouch.

• Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.

• Subject who has short bowel syndrome.

• Chronic recurring infections or active Tuberculosis (TB).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Gastroenterology Associates O.C /ID# 137282	Birmingham	Alabama	United States	35209
2	Digestive Health Specialists of the Southeast /ID# 122483	Dothan	Alabama	United States	36305
3	Moore UC San Diego Cancer Center /ID# 119053	La Jolla	California	United States	92093
4	Axis Clinical Trials /ID# 130390	Los Angeles	California	United States	90036
5	Rocky Mountain Gastroenterology /ID# 119038	Wheat Ridge	Colorado	United States	80033
6	Medical Research Ctr CT /ID# 119037	Hamden	Connecticut	United States	06518
7	Gastroenterology Group Naples /ID# 122493	Naples	Florida	United States	34102
8	Internal Med Specialists /ID# 137737	Orlando	Florida	United States	32806
9	Shafran Gastroenterology Ctr /ID# 119057	Winter Park	Florida	United States	32789
10	Winship Cancer Institute of Emory University /ID# 136851	Atlanta	Georgia	United States	30322
11	Atlanta Gastro Assoc /ID# 119065	Atlanta	Georgia	United States	30342
12	Gastroenterology Associates of Central Georgia, LLC /ID# 119056	Macon	Georgia	United States	31201
13	Northwestern University Feinberg School of Medicine /ID# 119043	Chicago	Illinois	United States	60611-2927
14	University of Chicago DCAM /ID# 119077	Chicago	Illinois	United States	60637-1443
15	Carle Foundation Hospital Digestive Health Research Center /ID# 136008	Urbana	Illinois	United States	61801
16	Louisana Research Center, LLC /ID# 136749	Shreveport	Louisiana	United States	71105-6800
17	Investigative Clinical Research /ID# 119033	Annapolis	Maryland	United States	21228
18	MGG Group Co, Inc.Chevy Chase Clinical Research /ID# 119042	Chevy Chase	Maryland	United States	20815
19	Commonwealth Clinical Studies /ID# 136850	Brockton	Massachusetts	United States	02302
20	University of Michigan Health Systems /ID# 119076	Ann Arbor	Michigan	United States	48109
21	Minnesota Gastroenterology, P. A. /ID# 137280	Plymouth	Minnesota	United States	55446
22	Mayo Clinic /ID# 122489	Rochester	Minnesota	United States	55905-0001
23	Kansas City Research Institute /ID# 119034	Kansas City	Missouri	United States	64131
24	Ctr for Digest and Liver Dis /ID# 119040	Mexico	Missouri	United States	65265
25	Albany Medical College /ID# 140200	Albany	New York	United States	12208
26	NYU Langone Long Island Clinical Research Associates /ID# 119035	Great Neck	New York	United States	11021
27	The Mount Sinai Hospital /ID# 127116	New York	New York	United States	10029
28	Charlotte Gastroenterology and Hepatology, PLLC /ID# 119041	Charlotte	North Carolina	United States	28207
29	Wake Research Associates, LLC /ID# 119029	Raleigh	North Carolina	United States	27612
30	Consultants for Clinical Res /ID# 119052	Cincinnati	Ohio	United States	45219
31	Gastro United of Tulsa /ID# 122485	Tulsa	Oklahoma	United States	74135
32	The Oregon Clinic, Gastroenterology - West /ID# 135272	Portland	Oregon	United States	97225
33	West Bay Clinical Research /ID# 138330	Warwick	Rhode Island	United States	02886
34	Medical University of South Carolina /ID# 138122	Charleston	South Carolina	United States	29425
35	Erlanger Institute for Clinical Research /ID# 129008	Chattanooga	Tennessee	United States	37403
36	Gastro One /ID# 119068	Germantown	Tennessee	United States	38138
37	Nashville Med Res Inst /ID# 119050	Nashville	Tennessee	United States	37205
38	Vanderbilt Univ Med Ctr /ID# 125501	Nashville	Tennessee	United States	37232-0011
39	Texas Digestive Disease Consultants - Dallas /ID# 138121	Dallas	Texas	United States	75231
40	Baylor College of Medicine /ID# 137277	Houston	Texas	United States	77030-3411
41	Austin Institute for Clinical Research /ID# 125500	Pflugerville	Texas	United States	78660
42	Texas Digestive Disease Consultants - Southlake /ID# 137283	Southlake	Texas	United States	76092
43	Advanced Research Institute /ID# 119048	Ogden	Utah	United States	84403
44	University of Utah /ID# 119062	Salt Lake City	Utah	United States	84112-5500
45	Gastro Assoc of Tidewater /ID# 135897	Chesapeake	Virginia	United States	23320
46	New River Valley Research Inst /ID# 127807	Christiansburg	Virginia	United States	24073
47	Wisconsin Center for Advanced Research, a division of GI Associates, LLC /ID# 119036	Milwaukee	Wisconsin	United States	53215
48	Froedtert Memorial Lutheran Hospital /ID# 119081	Milwaukee	Wisconsin	United States	53226-3522
49	KH der Elisabethinen Linz GmbH /ID# 126280	Linz	Oberoesterreich	Austria	4010
50	Medizinische Universitat Wien /ID# 126279	Vienna	Wien	Austria	1090
51	Medizinische Universitat Innsbruck,Universitatsklinik fur Innere Medizin 1 /ID# 126249	Innsbruck		Austria	6020
52	LKH Salzburg and Paracelsus /ID# 126248	Salzburg		Austria	5020
53	Krankenhaus der Barmherzigen Bruder /ID# 126270	St Veit An Der Glan		Austria	9300
54	AZ Maria Middelares /ID# 126194	Ghent		Belgium	9000
55	AZ Sint-Lucas /ID# 126242	Ghent		Belgium	9000
56	UZ Leuven /ID# 126240	Leuven		Belgium	3000
57	CHU de Liege /ID# 126241	Liege		Belgium	4000
58	AZ-Delta /ID# 126195	Roeselare		Belgium	8800
59	University of Calgary Cumming School of Medicine Adult Cystic Fibrosis Clinic /ID# 119017	Calgary	Alberta	Canada	T2N 4Z6
60	University of Alberta /ID# 119022	Edmonton	Alberta	Canada	T6G 2X8
61	Winnipeg Regional Health Authority /ID# 119015	Winnipeg	Manitoba	Canada	R3A 1R9
62	Qe Ii Hsc /Id# 127115	Halifax	Nova Scotia	Canada	B3H 1V7
63	London Health Sciences Centre - University Hospital /ID# 119026	London	Ontario	Canada	N6A 5A5
64	Medicor Research Inc /ID# 119024	Sudbury	Ontario	Canada	P3E 5M4
65	Toronto Digestive Disease Asso /ID# 119019	Vaughan	Ontario	Canada	L4L 4Y7
66	Montreal General Hospital - McGill University Health Center /ID# 119025	Montreal	Quebec	Canada	H3G 1A4
67	Fakultni Nemocnice Olomouc /ID# 126264	Olomouc	Olomoucky Kraj	Czechia	779 00
68	Nemocnice Ceske Budejovice a.s. /ID# 126266	Ceske Budejovice		Czechia	370 01
69	Hepato-Gastroenterologie HK s.r.o. /ID# 126269	Hradec Kralove		Czechia	500 12
70	ISCARE a.s. /ID# 137977	Praha 9		Czechia	190 00
71	Krajska zdravotni a.s. Masarykova nemocnice v Usti nad Labem o.z. /ID# 138331	Usti Nad Labem		Czechia	401 13
72	Herlev Hospital /ID# 127741	Herlev	Hovedstaden	Denmark	2730
73	Silkeborg Hospital /ID# 126251	Silkeborg		Denmark	8600
74	CHRU Lille - Hopital Claude Huriez /ID# 127743	Lille CEDEX	Hauts-de-France	France	59045
75	CHU NANCY - Hopital Brabois Adultes /ID# 127742	Vandoeuvre les Nancy CEDEX	Meurthe-et-Moselle	France	54511
76	CHU Amiens-Picardie Site Sud /ID# 126237	Amiens CEDEX 1	Somme	France	80054
77	Centre Hospitalier Universitaire de Grenoble - Hopital Michallon /ID# 126200	Grenoble		France	38043
78	Hopital l'Archet 2 /ID# 126238	Nice		France	06202
79	CHU de Saint-Etienne, Hopital Nord /ID# 134450	SAINT-ETIENNE Cedex 1		France	42270
80	Hopital Rangueil /ID# 126239	Toulouse		France	31059
81	Universitaetsklinikum Schleswig-Holstein /ID# 126260	Kiel	Schleswig-Holstein	Germany	24105
82	Charite Universitaetsmedizin Berlin /ID# 126196	Berlin		Germany	10117
83	Private Practice - Dr. Michael R. MroB Dipl. med. S. Schache /ID# 126257	Berlin		Germany	10318
84	Israelitisches Krankenhaus Hamburg /ID# 136549	Hamburg		Germany	22297
85	Asklepios Westklinikum Hamburg /ID# 126275	Hamburg		Germany	22559
86	Universitaetsklinikum Jena /ID# 126261	Jena		Germany	07747
87	EUGASTRO GmbH /ID# 126259	Leipzig		Germany	04103
88	Universitatsklinikum Magdeburg /ID# 126256	Magdeburg		Germany	39120
89	Gastro Campus Research GbR /ID# 126274	Munster		Germany	48159
90	Semmelweis Egyetem /ID# 137896	Budapest		Hungary	1085
91	Magyar Elhizastudomanyi KKft. /ID# 126276	Budapest		Hungary	1124
92	Pecsi Tudomanyegyetem Klinikai l.sz. Belgyogyaszati Klinika /ID# 137895	Pecs		Hungary	7624
93	University of Szeged /ID# 126263	Szeged		Hungary	6720
94	Rabin Medical Center /ID# 126198	Petakh Tikva	Tel-Aviv	Israel	4941492
95	Soroka University Medical Center /ID# 126243	Be'er Sheva		Israel	84101
96	Gastroenterology Institute, Division of Medicine /ID# 126245	Jerusalem		Israel	91120
97	Kaplan Medical Center /ID# 126246	Rehovot		Israel	76100
98	UOSD - Azienda Ospedaliera San Camillo Forlanini /ID# 127745	Rome	Lazio	Italy	00152
99	Policlinico Agostino Gemelli /ID# 127746	Rome	Lazio	Italy	00168
100	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 126221	Milan	Lombardia	Italy	20122
101	IBD Center - IRCCS Istituto Clinico Humanitas /ID# 126226	Rozzano	Milano	Italy	20089
102	Azienda Ospedaliera Spedali Civili /ID# 127744	Brescia		Italy	25123
103	Azienda Ospedaliera di Padova /ID# 126267	Padua		Italy	35128
104	Fondazione di Religione e di Culto Casa Sollievo della Sofferenza /ID# 129856	San Giovanni Rotondo		Italy	71013
105	Academisch Medical center Amsterdam /ID# 126227	Amsterdam	Noord-Holland	Netherlands	1105 AZ
106	Erasmus Medisch Centrum /ID# 126228	Rotterdam		Netherlands	3015 CE
107	Sint Franciscus Gasthuis /ID# 127877	Rotterdam		Netherlands	3045 PM
108	Centrum.Medyczne. Szpital Swietej Rodziny /ID# 137974	Lodz	Lodzkie	Poland	90-302
109	Endoterapia PFG sp. z o.o. /ID# 126199	Warszawa	Mazowieckie	Poland	02-653
110	Centrum Endoskopii Zabiegowej /ID# 126272	Bydgoszcz		Poland	85-168
111	Centrum Medyczne sw. Lukasza Sp. z o.o. /ID# 126271	Czestochowa		Poland	42-200
112	KO-Med Centra Kliniczne Pulawi /ID# 126278	Pulawy		Poland	24-100
113	NZOZ Vivamed /ID# 126255	Warsaw		Poland	03-580
114	School of Medicine University of Puerto Rico-Medical Science Campus /ID# 137735	San Juan		Puerto Rico	00935
115	Institutul Clinic Fundeni /ID# 127747	Sector 2	Bucuresti	Romania	022328
116	Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL /ID# 126277	Brasov		Romania	500283
117	Tvm Med Serv Srl /Id# 126268	Cluj		Romania	400132
118	Cabinet Medical Dr. Fratila SRL /ID# 126247	Oradea		Romania	410167
119	Salvo-san Ciobanca SRL / Medicina Interna /ID# 126224	Zalau		Romania	450117
120	Gastroenterologicke centrum ASSIDUO a IBD centrum /ID# 126262	Bratislava		Slovakia	831 04
121	Gastroenterologicka ambulancia /ID# 137964	Bratislava		Slovakia	851 01
122	Vseobecna Nemocnica s poliklinikou Lucenec n.o. /ID# 127748	Lucenec		Slovakia	984 01
123	Poliklinika Libris /ID# 126222	Nove Mesto Nad Vahom		Slovakia	915 01
124	Hospital Parc Tauli de Sabadell /ID# 138124	Sabadell	Barcelona	Spain	08208
125	Hospital Universitario Puerta de Hierro, Majadahonda /ID# 140425	Majadahonda	Madrid	Spain	28222
126	Hospital Clinic /ID# 127749	Barcelona		Spain	08036
127	Hospital Universitario de Girona Doctor Josep Trueta /ID# 137976	Girona		Spain	17007
128	Hospital de Leon /ID# 141675	Leon		Spain	24071
129	Hospital Clinico Universitario San Carlos /ID# 126253	Madrid		Spain	28040
130	Complejo Hospitalario Universitario de Pontevedra /ID# 138126	Pontevedra		Spain	36071
131	Hospital Clinico Universitario Lozano Blesa /ID# 126252	Zaragoza		Spain	50009
132	Kantonsspital St. Gallen /ID# 127750	St. Gallen	Sankt Gallen	Switzerland	9007
133	Universitaetsspital Zuerich /ID# 127751	Zurich	Zuerich	Switzerland	8006
134	State Institution L. T. Malaya Therapy National Institution of NAMS of Ukraine /ID# 127753	Kharkiv	Kharkivska Oblast	Ukraine	61039
135	Public Institution Kherson City Clinical Hospital named after le.le. Karabelesha /ID# 127754	Kherson		Ukraine	73000
136	Kyiv City Clinical Hospital No.8 /ID# 126232	Kiev		Ukraine	04201
137	Lviv Regional Clinical Hospital /ID# 126234	Lviv		Ukraine	79011
138	Public Institution 6th City Clinical Hospital /ID# 126236	Zaporizhzhia		Ukraine	69035
139	Guy's and St Thomas' NHS Found /ID# 144366	London	London, City Of	United Kingdom	SE1 9RT
140	Norfolk and Norwich Univ Hosp /ID# 126197	Norwich	Norfolk	United Kingdom	NR4 7UY
141	Hull University Teaching Hospitals NHS Trustust /ID# 126265	Hull		United Kingdom	HU8 9HE
142	University Hospital Southampton NHS Fundation Trust /ID# 126225	Southampton		United Kingdom	SO16 6YD
143	The Royal Wolverhampton NHS Tr /ID# 126201	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Nov 27, 2018
• Statistical Analysis Plan - Nov 15, 2019

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02065570
• Other Study ID Numbers: M14-115; 2013-001746-33
• First Posted: Feb 19, 2014
• Last Update Posted: Feb 18, 2021
• Last Verified: Feb 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
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: Crohn's Disease
• Additional relevant MeSH terms: Crohn Disease; Adalimumab

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 3:2 ratio at Baseline to receive a higher induction adalimumab regimen or standard induction adalimumab regimen during the double-blind Induction Study. At Week 12, participants were re-randomized in a 1:1 ratio to a double-blind exploratory treatment regimen (adalimumab clinically adjusted [CA] regimen or adalimumab therapeutic drug monitoring [TDM] regimen).

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose	Maintenance: Clinically Adjusted (CA) Regimen	Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.	Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose could be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.	At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM are determined by protocol-established dose adjustment criteria. Doses are determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 receive 40 mg ew.
Period Title: Induction Study
STARTED	206	308	0	0
COMPLETED	192	287	0	0
NOT COMPLETED	14	21	0	0
Period Title: Induction Study
STARTED	0	0	109	109
COMPLETED	0	0	87	90
NOT COMPLETED	0	0	22	19

Baseline Characteristics

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose	Total
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.	Total of all reporting groups
Overall Participants	206	308	514
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.4 (12.79)	36.4 (13.02)	36.4 (12.92)
Sex: Female, Male (Count of Participants)
Female	109 52.9%	158 51.3%	267 51.9%
Male	97 47.1%	150 48.7%	247 48.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 2.4%	10 3.2%	15 2.9%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	201 97.6%	298 96.8%	499 97.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.3%	1 0.2%
Asian	5 2.4%	6 1.9%	11 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	18 8.7%	11 3.6%	29 5.6%
White	182 88.3%	288 93.5%	470 91.4%
More than one race	1 0.5%	1 0.3%	2 0.4%
Unknown or Not Reported	0 0%	1 0.3%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission at Week 4
Description	Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	43.7 21.2%	43.5 14.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.939
	Comments	Adjusted for previous infliximab use (or prior anti-tumor necrosis factor (TNF) use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -8.1 to 8.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

2. Primary Outcome

Title	Percentage of Participants With Endoscopic Response at Week 12
Description	Endoscopic response was scored using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score > 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline) at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	39.3 19.1%	42.9 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.462
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; -5.3 to 11.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

3. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. Serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. TEAEs: any event that began or worsened in severity after the first dose of study drug in the induction or maintenance study. Events with unknown severity were counted as severe. Events with unknown relationship to study drug were counted as drug-related.
Time Frame	From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).

Outcome Measure Data

Analysis Population Description

Safety Set: all participants who received at least one injection of study drug.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose	Maintenance: Clinically Adjusted (CA) Regimen	Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
Arm/Group Description	Participants were randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, and then matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.	Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to ew starting as early as Week 14 and up to Week 54 based on CDAI or hs-CRP values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.	At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM are determined by protocol-established dose adjustment criteria. Doses are determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 receive 40 mg ew.
Measure Participants	206	308	109	109
Any TEAE	133 64.6%	185 60.1%	77 15%	76 NaN
TEAE w/reasonable possibility of being related to study drug	54 26.2%	75 24.4%	29 5.6%	33 NaN
Any severe TEAE	13 6.3%	17 5.5%	7 1.4%	6 NaN
Any SAE	10 4.9%	14 4.5%	5 1%	7 NaN
Any TEAE leading to discontinuation of study drug	8 3.9%	13 4.2%	8 1.6%	9 NaN
Any TEAE leading to death	0 0%	0 0%	0 0%	0 NaN
Deaths	0 0%	0 0%	0 0%	0 NaN

4. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12
Description	CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	35.0 17%	39.0 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -3.6 to 12.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

5. Secondary Outcome

Title	Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12
Description	Clinical response was scored using CDAI, which assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline. Endoscopic response was scored using the SES-CD, which evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score >50% from Baseline (or for Baseline SES-CD of 4, at least a 2-point reduction from Baseline) at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	20.4 9.9%	22.1 7.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.610
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -5.1 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

6. Secondary Outcome

Title	Percentage of Participants With Clinical Remission at Week 12
Description	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	51.5 25%	62.3 20.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	11.2
	Confidence Interval	(2-Sided) 95%; 2.9 to 19.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

7. Secondary Outcome

Title	Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline
Description	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Participants taking corticosteroids at Baseline.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	100	155
Number [percentage of participants]	48.0 23.3%	52.9 17.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.336
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95%; -6.2 to 18.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

8. Secondary Outcome

Title	Percentage of Participants With Endoscopic Remission at Week 12
Description	Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	26.2 12.7%	28.6 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.694
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -6.1 to 9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

9. Secondary Outcome

Title	Change From Baseline in Fecal Calprotectin Level at Week 4
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Participants with a baseline and Week 4 assessment. Observed cases.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	152	252
Mean (Standard Deviation) [µg/g]	-1045.7 (1648.51)	-1157.0 (2000.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.946
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	LS Mean of Difference
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; -192.3 to 205.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	27.7 13.4%	32.5 10.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.293
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; -3.5 to 11.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

11. Secondary Outcome

Title	Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4
Description	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	11.2 5.4%	14.3 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.304
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -2.7 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

12. Secondary Outcome

Title	Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g and Endoscopic Remission at Week 12
Description	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	7.3 3.5%	11.7 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

13. Secondary Outcome

Title	Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12
Description	The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	16.0 7.8%	20.1 6.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -2.9 to 10.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

14. Secondary Outcome

Title	Percentage of Participants With Clinical Response at Week 4
Description	Clinical response was scored using CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from baseline.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	70.9 34.4%	74.4 24.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.353
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	3.7
	Confidence Interval	(2-Sided) 95%; -4.1 to 11.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

15. Secondary Outcome

Title	Percentage of Participants With Clinical Response at Week 12
Description	Clinical response was scored using CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	74.8 36.3%	83.4 27.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	8.9
	Confidence Interval	(2-Sided) 95%; 1.8 to 16.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

16. Secondary Outcome

Title	Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4
Description	The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	71.4 34.7%	74.7 24.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.394
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -4.4 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).

17. Secondary Outcome

Title	Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12
Description	The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	73.3 35.6%	76.9 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.349
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -4.0 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose)

18. Secondary Outcome

Title	Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12
Description	The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent to Treat Population: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Induction: Standard Induction Dose	Induction: Higher Induction Dose
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Measure Participants	206	308
Number [percentage of participants]	68.4 33.2%	76.0 24.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Induction: Standard Induction Dose, Induction: Higher Induction Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments	Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted risk difference
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95%; -0.1 to 15.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose)

Adverse Events

Time Frame	From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).
Arm/Group Title	Induction: Standard Induction Dose		Induction: Higher Induction Dose		Maintenance: Clinically Adjusted (CA) Regimen		Maintenance: Therapeutic Drug Management (TDM) Regimen
Arm/Group Description	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.		Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.		Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to ew starting as early as Week 14 and up to Week 54 based on CDAI or hs-CRP values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.		At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM are determined by protocol-established dose adjustment criteria. Doses are determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 receive 40 mg ew.
All Cause Mortality
	Induction: Standard Induction Dose		Induction: Higher Induction Dose		Maintenance: Clinically Adjusted (CA) Regimen		Maintenance: Therapeutic Drug Management (TDM) Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/206 (0%)		0/308 (0%)		0/109 (0%)		0/109 (0%)
Serious Adverse Events
	Induction: Standard Induction Dose		Induction: Higher Induction Dose		Maintenance: Clinically Adjusted (CA) Regimen		Maintenance: Therapeutic Drug Management (TDM) Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/206 (4.9%)		14/308 (4.5%)		5/109 (4.6%)		7/109 (6.4%)
Eye disorders
SCLERITIS	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
UVEITIS	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	1/206 (0.5%)	1	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
CROHN'S DISEASE	3/206 (1.5%)	3	3/308 (1%)	3	2/109 (1.8%)	2	1/109 (0.9%)	1
FAECALOMA	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
GASTROINTESTINAL INFLAMMATION	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
INTESTINAL HAEMORRHAGE	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
INTESTINAL OBSTRUCTION	0/206 (0%)	0	2/308 (0.6%)	2	1/109 (0.9%)	1	0/109 (0%)	0
LARGE INTESTINAL STENOSIS	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
SMALL INTESTINAL OBSTRUCTION	1/206 (0.5%)	2	0/308 (0%)	0	1/109 (0.9%)	1	0/109 (0%)	0
SUBILEUS	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
Infections and infestations
ABDOMINAL ABSCESS	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
ABSCESS LIMB	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
ACQUIRED IMMUNODEFICIENCY SYNDROME	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
CELLULITIS	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
INFECTIOUS MONONUCLEOSIS	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
INTESTINAL TUBERCULOSIS	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
PNEUMOCYSTIS JIROVECII PNEUMONIA	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
PYELONEPHRITIS	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
SEPSIS	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
URINARY TRACT INFECTION	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	1/109 (0.9%)	1
VARICELLA	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
Injury, poisoning and procedural complications
CLAVICLE FRACTURE	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
HIP FRACTURE	0/206 (0%)	0	0/308 (0%)	0	1/109 (0.9%)	1	0/109 (0%)	0
RADIUS FRACTURE	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
ROAD TRAFFIC ACCIDENT	0/206 (0%)	0	1/308 (0.3%)	1	1/109 (0.9%)	1	0/109 (0%)	0
TRAUMATIC LIVER INJURY	0/206 (0%)	0	0/308 (0%)	0	1/109 (0.9%)	1	0/109 (0%)	0
Metabolism and nutrition disorders
HYPOKALAEMIA	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
HYPOVOLAEMIA	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
BACK PAIN	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PAPILLARY RENAL CELL CARCINOMA	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
Nervous system disorders
AMNESIA	1/206 (0.5%)	1	0/308 (0%)	0	0/109 (0%)	0	0/109 (0%)	0
CEREBRAL INFARCTION	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
Psychiatric disorders
DEPRESSION	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	1/109 (0.9%)	1
SUICIDAL IDEATION	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
Renal and urinary disorders
HYDRONEPHROSIS	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
NEPHROLITHIASIS	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
Skin and subcutaneous tissue disorders
DRUG ERUPTION	0/206 (0%)	0	0/308 (0%)	0	0/109 (0%)	0	1/109 (0.9%)	1
Surgical and medical procedures
SELECTIVE ABORTION	0/206 (0%)	0	1/308 (0.3%)	1	0/109 (0%)	0	0/109 (0%)	0
Other (Not Including Serious) Adverse Events
	Induction: Standard Induction Dose		Induction: Higher Induction Dose		Maintenance: Clinically Adjusted (CA) Regimen		Maintenance: Therapeutic Drug Management (TDM) Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/206 (26.2%)		58/308 (18.8%)		41/109 (37.6%)		33/109 (30.3%)
Gastrointestinal disorders
CROHN'S DISEASE	12/206 (5.8%)	14	14/308 (4.5%)	15	16/109 (14.7%)	20	15/109 (13.8%)	17
DIARRHOEA	3/206 (1.5%)	3	2/308 (0.6%)	2	6/109 (5.5%)	7	4/109 (3.7%)	4
NAUSEA	15/206 (7.3%)	17	9/308 (2.9%)	10	5/109 (4.6%)	7	3/109 (2.8%)	3
Infections and infestations
NASOPHARYNGITIS	9/206 (4.4%)	11	19/308 (6.2%)	21	15/109 (13.8%)	15	10/109 (9.2%)	12
Musculoskeletal and connective tissue disorders
ARTHRALGIA	16/206 (7.8%)	19	10/308 (3.2%)	10	8/109 (7.3%)	8	4/109 (3.7%)	5
Nervous system disorders
DIZZINESS	11/206 (5.3%)	13	2/308 (0.6%)	2	0/109 (0%)	0	0/109 (0%)	0
HEADACHE	18/206 (8.7%)	24	17/308 (5.5%)	19	9/109 (8.3%)	9	8/109 (7.3%)	18

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.