Study to Evaluate the Safety and Efficacy of Adalimumab in Chinese Subjects With Moderate to Severe Crohn's Disease

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02499783
• Collaborator: (none)
• Enrollment: 205
• Arms: 2
• Actual Duration (Months): 28

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of adalimumab induction and maintenance treatment in subjects with moderately to severely active Crohn's disease in China.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Biological: adalimumab; Other: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 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, Placebo Controlled Study to Evaluate the Efficacy and Safety of Adalimumab for the Induction and Maintenance of Clinical Remission in Chinese Patients With Moderately to Severely Active Crohn's Disease and Elevated High-Sensitivity C-reactive Protein
• Actual Study Start Date: Aug 17, 2015
• Actual Primary Completion Date: May 19, 2017
• Actual Study Completion Date: Dec 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo Induction Regimen Double-blind period (Weeks 0-8): Placebo at Weeks 0 and 2, followed by adalimumab 160 mg at Week 4, 80 mg at Week 6. Open label period: adalimumab 40 mg every other week (eow) from Week 8 through last dose at Week 24.	Biological: adalimumab; subcutaneous injections of adalimumab; Other Names: Humira ; Other: placebo; subcutaneous injections of placebo
Experimental: Adalimumab Induction Regimen Double-blind period (Weeks 0-8): adalimumab 160 mg at Weeks 0 and 80 mg at Week 2, followed by adalimumab 40 mg at Week 4 and Week 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.	Biological: adalimumab; subcutaneous injections of adalimumab; Other Names: Humira

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) at Week 4 [Week 4]

   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.

Secondary Outcome Measures

1. Percentage of Participants Who Achieved Clinical Remission at Week 26 (CDAI < 150) in Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8 [Week 26]

   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.

2. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus a Reduction in Hs-CRP of at Least 50% From Baseline at Week 4 [Week 4]

   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.

3. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus a Reduction in Hs-CRP of At Least 50% From Baseline at Week 26 in Participants Who Achieved Clinical Response Plus at Least 30% Reduction in Hs-CRP From Baseline at Week 8 [Week 26]

   Clinical response is defined as a decrease in CDAI ≥ 70 Points from Baseline 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.

4. Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 26 in Participants Who Were Taking Steroids at Baseline and Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8 [Week 26]

   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.

5. Percentage of Participants Who Discontinued Corticosteroid Use and Achieved CDAI < 150 Plus a Reduction in Hs-CRP of ≥ 50% From Baseline (BL) at Week 26 in Participants Taking Steroids at BL and Who Achieved CDAI Decrease and Hs-CRP Reduction at Week 8 [Week 26]

   Percentage of participants who discontinued corticosteroid use and achieved clinical remission (CDAI < 150) plus a reduction in hs-CRP of at least 50% from Baseline at Week 26 in participants who were taking steroids at Baseline and who achieved clinical response (decrease in CDAI of ≥ 70 points from Baseline) plus a reduction in hs-CRP of ≥ 30% From Baseline at Week 8. 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.

6. Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 4 [Week 4]

   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.

7. Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Plus a Reduction in Hs-CRP of at Least 30% From Baseline at Week 4 [Week 4]

   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.

8. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) and Hs-CRP < 3 mg/L at Week 4 [Week 4]

   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.

9. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150), Hs-CRP < 3 mg/L at Week 26 in Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8 [Week 26]

   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.

10. Percentage of Participants Who Achieved Inflammatory Bowel Disease Questionnaire (IBDQ) Remission (IBDQ ≥ 170 Points) 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). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.

11. Percentage of Participants Who Achieved IBDQ Remission (IBDQ ≥ 170 Points) at Week 26 in Participants With Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8 [Week 26]

    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). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life. 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.

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

13. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150), Hs-CRP < 3 mg/L and Fecal Calprotectin < 250 μg/g at Week 4 [Week 4]

    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.

14. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150), Hs-CRP < 3 mg/L and Fecal Calprotectin < 250 μg/g at Week 26 in Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8 [Week 26]

    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.

15. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Over Double-Blind Weeks 0-4 [Weeks 2, 4]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

16. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Over Time (Any Adalimumab Set) [Baseline (Week 0 of adalimumab), Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)

17. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus A Reduction in Hs-CRP of at Least 50% From Baseline Over Double-Blind Weeks 0-4 [Weeks 2, 4]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

18. Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus a Reduction in Hs-CRP of at Least 50% From Baseline Over Time (Any Adalimumab Set) [Weeks 2, 4, 6, 8, 12, 16, 20, 26]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)

19. Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Over Double-Blind Weeks 0-4 [Weeks 2, 4]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

20. Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Over Time (Any Adalimumab Set) [Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)

21. Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Plus a Reduction in Hs-CRP of at Least 30% From Baseline Over Double-Blind Weeks 0-4 [Weeks 2, 4]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

22. Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Plus a Reduction in Hs-CRP of at Least 30% From Baseline Over Time (Any Adalimumab Set) [Weeks 2, 4, 6, 8, 12, 16, 20, 26]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)

23. Change From Baseline in CDAI Over Double-Blind Weeks 0-4 [Baseline, Weeks 2, 4]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

24. Change From Baseline in CDAI Over Time (Any Adalimumab Set) [Baseline (Week 0 of adalimumab), Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26]

    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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)

25. Change From Baseline in Hs-CRP Level Over Double-Blind Weeks 0-4 [Baseline, Weeks 2, 4]

    The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

26. Change From Baseline in Hs-CRP Level Over Time (Any Adalimumab Set) [Baseline (Week 0 of adalimumab), Weeks 2, 4, 6, 8, 12, 16 20, 26]

    The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)

27. Change From Baseline in Fecal Calprotectin Level Over Time (Any Adalimumab Set) [Baseline (Week 0 of adalimumab), Weeks 4, 8, 26]

    The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects of Chinese descent with full Chinese parentage.

• Diagnosis of Crohn's disease (CD) for at least 3 months prior to Week 0.

• Crohn's Disease Activity Index (CDAI) greater than or equal to 220 and less than or equal to 450 despite treatment with oral corticosteroids and/or immunosuppressants.

• Subject has a negative Tuberculosis (TB) Screening Assessment.

• Subject has elevated high sensitivity C-reactive protein (hs-CRP) during the Screening Period.

Exclusion Criteria:

• Subject with ulcerative colitis or indeterminate colitis.

• Subject who has had a surgical bowel resection within the past 6 months or who is planning any resection at any time point in the future.

• Subject with an ostomy or ileoanal pouch.

• Subject who has short bowel syndrome.

• Subject with symptomatic known obstructive strictures.

• Subject with an internal or external fistula (with the exception of an anal fistula without abscess).

• Active, or chronic or recurring infections, or active tuberculosis.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Oct 19, 2015
• Statistical Analysis Plan - Oct 26, 2017

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02499783
• Other Study ID Numbers: M14-233
• First Posted: Jul 16, 2015
• Last Update Posted: Jan 4, 2019
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: China; Tumor necrosis factor (TNF)-alpha; Biologic
• Additional relevant MeSH terms: Crohn Disease; Adalimumab

Study Results

Participant Flow

Arm/Group Title	Double-Blind (DB) Period: Adalimumab 160/80/40 mg	DB Period: Placebo Followed by Adalimumab 160/80 mg	Open-Label (OL) Period: Adalimumab 40 mg
Arm/Group Description	Double-blind adalimumab 160 mg at Week 0; 80 mg at Week 2; 40 mg at Weeks 4 and 6.	Double-blind placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6.	Open-label adalimumab 40 mg every other week (eow) from Week 8 through last dose at Week 24.
Period Title: DB Period/Placebo-Controlled: Weeks 0-4
STARTED	102	103	0
COMPLETED	98	98	0
NOT COMPLETED	4	5	0
Period Title: DB Period/Placebo-Controlled: Weeks 0-4
STARTED	102	103	0
COMPLETED	92	96	0
NOT COMPLETED	10	7	0
Period Title: DB Period/Placebo-Controlled: Weeks 0-4
STARTED	0	0	188
COMPLETED	0	0	159
NOT COMPLETED	0	0	29

Baseline Characteristics

Arm/Group Title	Double-Blind Period: Adalimumab 160/80/40 mg	Double-Blind Period: Placebo Followed by Adalimumab 160/80 mg	Total
Arm/Group Description	Double-blind adalimumab 160 mg at Week 0; 80 mg at Week 2; 40 mg at Weeks 4 and 6.	Double-blind placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6.	Total of all reporting groups
Overall Participants	102	103	205
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.2 (10.24)	32.6 (9.50)	32.9 (9.85)
Sex: Female, Male (Count of Participants)
Female	35 34.3%	30 29.1%	65 31.7%
Male	67 65.7%	73 70.9%	140 68.3%
Race/Ethnicity, Customized (Count of Participants)
Chinese	102 100%	103 100%	205 100%
Crohn's Disease Activity Index (CDAI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	272.05 (48.117)	274.71 (49.055)	273.38 (48.490)
High Sensitivity C-Reactive Protein (Hs-CRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	23.93 (24.595)	27.12 (31.526)	25.53 (28.266)
Fecal Calprotectin (μg/g) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μg/g]	1481.8 (809.29)	1435.4 (766.37)	1458.4 (786.20)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) at Week 4
Description	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.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Number [percentage of participants]	6.8 6.7%	37.3 36.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	30.4
	Confidence Interval	(2-Sided) 95%; 19.2 to 41.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

2. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission at Week 26 (CDAI < 150) in Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	144
Number [percentage of participants]	64.6 63.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	One Sample Exact Test
	Comments	The one sample Exact test was performed by comparing it to the clinically meaningful remission rate of 30%.
Method of Estimation	Estimation Parameter	Risk Difference Compared to 30%
	Estimated Value	34.6
	Confidence Interval	(2-Sided) 95%; 26.2 to 42.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus a Reduction in Hs-CRP of at Least 50% From Baseline at Week 4
Description	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.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	103	102
Number [percentage of participants]	0 0%	33.3 32.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	33.4
	Confidence Interval	(2-Sided) 95%; 23.2 to 43.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.

4. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus a Reduction in Hs-CRP of At Least 50% From Baseline at Week 26 in Participants Who Achieved Clinical Response Plus at Least 30% Reduction in Hs-CRP From Baseline at Week 8
Description	Clinical response is defined as a decrease in CDAI ≥ 70 Points from Baseline 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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) plus at least 30% reduction in hs-CRP from Baseline at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	120
Number [percentage of participants]	55.0 53.9%

5. Secondary Outcome

Title	Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 26 in Participants Who Were Taking Steroids at Baseline and Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who were taking steroids at Baseline and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	43
Number [percentage of participants]	62.8 61.6%

6. Secondary Outcome

Title	Percentage of Participants Who Discontinued Corticosteroid Use and Achieved CDAI < 150 Plus a Reduction in Hs-CRP of ≥ 50% From Baseline (BL) at Week 26 in Participants Taking Steroids at BL and Who Achieved CDAI Decrease and Hs-CRP Reduction at Week 8
Description	Percentage of participants who discontinued corticosteroid use and achieved clinical remission (CDAI < 150) plus a reduction in hs-CRP of at least 50% from Baseline at Week 26 in participants who were taking steroids at Baseline and who achieved clinical response (decrease in CDAI of ≥ 70 points from Baseline) plus a reduction in hs-CRP of ≥ 30% From Baseline at Week 8. 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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who were taking steroids at Baseline and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) plus a reduction in hs-CRP of at least 30% from Baseline at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	33
Number [percentage of participants]	57.6 56.5%

7. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 4
Description	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.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	103	102
Number [percentage of participants]	27.2 26.7%	67.6 65.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	40.4
	Confidence Interval	(2-Sided) 95%; 26.7 to 54.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.

8. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Plus a Reduction in Hs-CRP of at Least 30% From Baseline at Week 4
Description	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.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	103	102
Number [percentage of participants]	11.7 11.5%	61.8 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	50.2
	Confidence Interval	(2-Sided) 95%; 36.9 to 63.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.

9. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) and Hs-CRP < 3 mg/L at Week 4
Description	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.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	103	102
Number [percentage of participants]	0 0%	27.5 26.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	27.6
	Confidence Interval	(2-Sided) 95%; 18.2 to 37.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.

10. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150), Hs-CRP < 3 mg/L at Week 26 in Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	144
Number [percentage of participants]	36.8 36.1%

11. Secondary Outcome

Title	Percentage of Participants Who Achieved Inflammatory Bowel Disease Questionnaire (IBDQ) Remission (IBDQ ≥ 170 Points) 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). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	103	102
Number [percentage of participants]	20.4 20%	40.2 39%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	19.6
	Confidence Interval	(2-Sided) 95%; 7.1 to 32.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.

12. Secondary Outcome

Title	Percentage of Participants Who Achieved IBDQ Remission (IBDQ ≥ 170 Points) at Week 26 in Participants With Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8
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). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life. 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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	144
Number [percentage of participants]	51.4 50.4%

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Observed cases.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	93	91
Mean (Standard Deviation) [μg/g]	-66.3 (844.89)	-499.5 (868.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	P-value for test of difference between adalimumab and placebo for mean change from Baseline using ANCOVA with Treatment, Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline, and Baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-385.2
	Confidence Interval	(2-Sided) 95%; -598.81 to -171.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150), Hs-CRP < 3 mg/L and Fecal Calprotectin < 250 μg/g at Week 4
Description	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.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2.
Measure Participants	103	102
Number [percentage of participants]	0 0%	9.8 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	9.8
	Confidence Interval	(2-Sided) 95%; 3.9 to 15.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by be stratified by Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline.

15. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150), Hs-CRP < 3 mg/L and Fecal Calprotectin < 250 μg/g at Week 26 in Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 8
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who were randomized and who achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	144
Number [percentage of participants]	16.0 15.7%

16. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Over Double-Blind Weeks 0-4
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Weeks 2, 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Week 2	7.8 7.6%	26.5 25.7%
Week 4	6.8 6.7%	37.3 36.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Clinical Remission at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	18.4
	Confidence Interval	(2-Sided) 95%; 8.2 to 28.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Clinical Remission at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	30.4
	Confidence Interval	(2-Sided) 95%; 19.2 to 41.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

17. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Over Time (Any Adalimumab Set)
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)
Time Frame	Baseline (Week 0 of adalimumab), Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	200
Baseline	3.0 2.9%
Week 2	31.5 30.9%
Week 4	40.0 39.2%
Week 6	48.0 47.1%
Week 8	55.5 54.4%
Week 10	45.5 44.6%
Week 12	56.5 55.4%
Week 14	51.5 50.5%
Week 16	56.0 54.9%
Week 18	48.5 47.5%
Week 20	53.0 52%
Week 22	52.5 51.5%
Week 24	49.0 48%
Week 26	53.9 52.8%

18. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus A Reduction in Hs-CRP of at Least 50% From Baseline Over Double-Blind Weeks 0-4
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Weeks 2, 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Week 2	1.0 1%	22.5 21.8%
Week 4	0 0%	33.3 32.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Clinical Remission (CDAI < 150) Plus A Reduction in HS-CRP of at Least 50% From Baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	21.4
	Confidence Interval	(2-Sided) 95%; 12.6 to 30.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Clinical Remission (CDAI < 150) Plus A Reduction in HS-CRP of at Least 50% From Baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	33.4
	Confidence Interval	(2-Sided) 95%; 23.2 to 43.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

19. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Plus a Reduction in Hs-CRP of at Least 50% From Baseline Over Time (Any Adalimumab Set)
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)
Time Frame	Weeks 2, 4, 6, 8, 12, 16, 20, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	200
Week 2	27.5 27%
Week 4	36.0 35.3%
Week 6	26.0 25.5%
Week 8	45.0 44.1%
Week 12	43.5 42.6%
Week 16	44.5 43.6%
Week 20	42.0 41.2%
Week 26	39.2 38.4%

20. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Over Double-Blind Weeks 0-4
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Weeks 2, 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Week 2	22.3 21.9%	44.1 42.8%
Week 4	27.2 26.7%	67.6 65.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	21.7
	Confidence Interval	(2-Sided) 95%; 8.7 to 34.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	40.4
	Confidence Interval	(2-Sided) 95%; 26.7 to 54.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

21. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Over Time (Any Adalimumab Set)
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)
Time Frame	Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	200
Week 2	45.0 44.1%
Week 4	59.0 57.8%
Week 6	60.0 58.8%
Week 8	64.5 63.2%
Week 10	54.5 53.4%
Week 12	58.0 56.9%
Week 14	54.5 53.4%
Week 16	58.0 56.9%
Week 18	49.5 48.5%
Week 20	54.5 53.4%
Week 22	50.0 49%
Week 24	52.9 51.9%
Week 26	59.8 58.6%

22. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Plus a Reduction in Hs-CRP of at Least 30% From Baseline Over Double-Blind Weeks 0-4
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Weeks 2, 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Non-responder imputation.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Week 2	8.7 8.5%	40.2 39%
Week 4	11.7 11.5%	61.8 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Decrease in CDAI ≥ 70 Points From Baseline Plus a Reduction in Hs-CRP of at Least 30% From Baseline at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	31.4
	Confidence Interval	(2-Sided) 95%; 19.6 to 43.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Decrease in CDAI ≥ 70 Points From Baseline Plus a Reduction in Hs-CRP of at Least 30% From Baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	50.2
	Confidence Interval	(2-Sided) 95%; 36.9 to 63.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference = (adalimumab 160/80 mg - placebo). Based on Cochran-Mantel-Haenszel test stratified by Crohn's disease severity (CDAI <= 300 and CDAI >300) at baseline and corticosteroid use at baseline.

23. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinical Response (Decrease in CDAI ≥ 70 Points From Baseline) Plus a Reduction in Hs-CRP of at Least 30% From Baseline Over Time (Any Adalimumab Set)
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)
Time Frame	Weeks 2, 4, 6, 8, 12, 16, 20, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Non-responder imputation.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	200
Week 2	41.5 40.7%
Week 4	55.0 53.9%
Week 6	35.5 34.8%
Week 8	55.5 54.4%
Week 12	49.5 48.5%
Week 16	51.0 50%
Week 20	45.5 44.6%
Week 26	52.0 51%

24. Secondary Outcome

Title	Change From Baseline in CDAI Over Double-Blind Weeks 0-4
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Baseline, Weeks 2, 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Observed cases.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Week 2	-30.97 (53.699)	-73.66 (63.267)
Week 4	-38.22 (60.918)	-104.56 (67.325)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Change From Baseline in CDAI at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	P-value for test of difference between adalimumab and placebo for mean change from Baseline using ANCOVA with Treatment, Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline, and Baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-43.34
	Confidence Interval	(2-Sided) 95%; -59.39 to -27.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Change From Baseline in CDAI at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	P-value for test of difference between adalimumab and placebo for mean change from Baseline using ANCOVA with Treatment, Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline, and Baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-66.63
	Confidence Interval	(2-Sided) 95%; -84.20 to -49.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline in CDAI Over Time (Any Adalimumab Set)
Description	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. The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)
Time Frame	Baseline (Week 0 of adalimumab), Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Observed cases.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	200
Week 2	-67.31 (67.268)
Week 4	-92.60 (74.666)
Week 6	-103.62 (79.094)
Week 8	-115.96 (83.900)
Week 10	-122.51 (82.991)
Week 12	-131.55 (76.754)
Week 14	-136.85 (76.459)
Week 16	-143.56 (72.597)
Week 18	-140.40 (77.473)
Week 20	-147.54 (72.352)
Week 22	-143.99 (77.972)
Week 24	-182.01 (54.588)
Week 26	-178.74 (54.277)

26. Secondary Outcome

Title	Change From Baseline in Hs-CRP Level Over Double-Blind Weeks 0-4
Description	The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Baseline, Weeks 2, 4

Outcome Measure Data

Analysis Population Description

ITT Set: all participants who were randomized. Observed cases.

Arm/Group Title	Double-Blind Period, Weeks 0 to 4: Placebo	Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
Arm/Group Description	Double-blind placebo at Weeks 0 and 2	Double-blind adalimumab 160 mg at Week 0 and 80 mg at Week 2
Measure Participants	103	102
Week 2	-4.149 (22.1944)	-16.474 (25.5491)
Week 4	-1.131 (18.8392)	-16.670 (19.9088)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Change From Baseline in hs-CRP Level at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	P-value for test of difference between adalimumab and placebo for mean change from Baseline using ANCOVA with Treatment, Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline, and Baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-13.921
	Confidence Interval	(2-Sided) 95%; -19.183 to -8.659
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind Period, Weeks 0 to 4: Placebo, Double-Blind Period, Weeks 0 to 4: Adalimumab 160/80 mg
	Comments	Change From Baseline in hs-CRP Level at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	P-value for test of difference between adalimumab and placebo for mean change from Baseline using ANCOVA with Treatment, Crohn's disease severity (CDAI <= 300, > 300) at Baseline and corticosteroid use at Baseline, and Baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-16.844
	Confidence Interval	(2-Sided) 95%; -21.206 to -12.483
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Change From Baseline in Hs-CRP Level Over Time (Any Adalimumab Set)
Description	The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment. (Note: the analysis window for the 'Any Adalimumab Set' is different from that used for the ITT population. For the Any Adalimumab Set, the Baseline Visit date is the date when the first dose of adalimumab was received, and was counted as Day 1 or Week 0.)
Time Frame	Baseline (Week 0 of adalimumab), Weeks 2, 4, 6, 8, 12, 16 20, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Observed cases.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	200
Week 2	-16.923 (23.8242)
Week 4	-17.064 (21.8366)
Week 6	-12.295 (20.9586)
Week 8	-14.565 (18.5093)
Week 12	-13.527 (19.9087)
Week 16	-13.504 (18.1452)
Week 20	-11.921 (18.4776)
Week 26	-12.308 (14.4531)

28. Secondary Outcome

Title	Change From Baseline in Fecal Calprotectin Level Over Time (Any Adalimumab Set)
Description	The analysis over time was performed for the DB placebo-controlled period (Week 0 to Week 4), with comparisons between active treatment and placebo groups. The analysis over time was also performed for Any Adalimumab set (the entire study on or after the first dose of adalimumab), with only summary statistics for adalimumab treatment.
Time Frame	Baseline (Week 0 of adalimumab), Weeks 4, 8, 26

Outcome Measure Data

Analysis Population Description

Any Adalimumab Set: all participants who received at least 1 injection of adalimumab. Observed cases.

Arm/Group Title	All Participants
Arm/Group Description	Double-blind period: placebo at Weeks 0 and 2, adalimumab 160 mg at Week 4, 80 mg at Week 6, OR Double-blind period: adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 and 6. Open label period: adalimumab 40 mg eow from Week 8 through last dose at Week 24.
Measure Participants	188
Week 4	-425.7 (940.04)
Week 8	-529.6 (913.50)
Week 26	-475.6 (978.07)

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs): from first dose of study drug through last dose (Week 24) plus 70 days.
Adverse Event Reporting Description	A TEAE during Week 0-4 of DB period=any event with an onset date on or after first dose of study drug and up to first dose of study drug at Week 4 or within 70 days after the last dose of study drug in Week0-4 of DB period for participants who discontinued prior to Week 4. A TEAE during DB or OL period of Any Adalimumab=any event with an onset date on or after first dose of adalimumab in the DB/OL periods and within 70 days after the last dose of study drug.
Arm/Group Title	Double-Blind Placebo Weeks 0-4		Double-Blind Adalimumab 160/80 mg Weeks 0-4		Any Adalimumab
Arm/Group Description	Double-blind placebo at Weeks 0 and 2.		Double-blind adalimumab 160/80 mg at Weeks 0 and 2.		Any adalimumab, from first dose of adalimumab to last dose at Week 24.
All Cause Mortality
	Double-Blind Placebo Weeks 0-4		Double-Blind Adalimumab 160/80 mg Weeks 0-4		Any Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		0/102 (0%)		0/200 (0%)
Serious Adverse Events
	Double-Blind Placebo Weeks 0-4		Double-Blind Adalimumab 160/80 mg Weeks 0-4		Any Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/103 (1%)		2/102 (2%)		36/200 (18%)
Blood and lymphatic system disorders
ANAEMIA	0/103 (0%)		1/102 (1%)		2/200 (1%)
Gastrointestinal disorders
ABDOMINAL MASS	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
ABDOMINAL PAIN	0/103 (0%)		0/102 (0%)		2/200 (1%)
ANAL FISTULA	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
CROHN'S DISEASE	0/103 (0%)		0/102 (0%)		17/200 (8.5%)
ENTEROVESICAL FISTULA	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
GASTROINTESTINAL FISTULA	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
GASTROINTESTINAL PERFORATION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
ILEAL PERFORATION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
ILEUS	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
INTESTINAL FISTULA	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
INTESTINAL MASS	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
INTESTINAL PERFORATION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
LARGE INTESTINE POLYP	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
LOWER GASTROINTESTINAL HAEMORRHAGE	1/103 (1%)		0/102 (0%)		0/200 (0%)
RECTAL POLYP	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
Infections and infestations
ABDOMINAL ABSCESS	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
COLONIC ABSCESS	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
GASTROINTESTINAL INFECTION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
LUNG INFECTION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
PERITONITIS	0/103 (0%)		0/102 (0%)		2/200 (1%)
TOXIC SHOCK SYNDROME	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
UPPER RESPIRATORY TRACT INFECTION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
URINARY TRACT INFECTION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
Injury, poisoning and procedural complications
CLAVICLE FRACTURE	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
Metabolism and nutrition disorders
MALNUTRITION	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
Skin and subcutaneous tissue disorders
PITYRIASIS ROSEA	0/103 (0%)		0/102 (0%)		1/200 (0.5%)
Surgical and medical procedures
ABORTION INDUCED	0/103 (0%)		1/102 (1%)		1/200 (0.5%)
Other (Not Including Serious) Adverse Events
	Double-Blind Placebo Weeks 0-4		Double-Blind Adalimumab 160/80 mg Weeks 0-4		Any Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/103 (17.5%)		25/102 (24.5%)		137/200 (68.5%)
Blood and lymphatic system disorders
LEUKOPENIA	1/103 (1%)		3/102 (2.9%)		22/200 (11%)
Gastrointestinal disorders
HAEMATOCHEZIA	0/103 (0%)		0/102 (0%)		10/200 (5%)
General disorders
PYREXIA	4/103 (3.9%)		1/102 (1%)		15/200 (7.5%)
Infections and infestations
INFLUENZA	1/103 (1%)		2/102 (2%)		13/200 (6.5%)
UPPER RESPIRATORY TRACT INFECTION	5/103 (4.9%)		1/102 (1%)		23/200 (11.5%)
VIRAL UPPER RESPIRATORY TRACT INFECTION	3/103 (2.9%)		4/102 (3.9%)		20/200 (10%)
Investigations
MYCOBACTERIUM TUBERCULOSIS COMPLEX TEST POSITIVE	3/103 (2.9%)		1/102 (1%)		13/200 (6.5%)
WHITE BLOOD CELL COUNT DECREASED	1/103 (1%)		6/102 (5.9%)		39/200 (19.5%)
Nervous system disorders
DIZZINESS	0/103 (0%)		4/102 (3.9%)		12/200 (6%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/103 (0%)		5/102 (4.9%)		16/200 (8%)
OROPHARYNGEAL PAIN	0/103 (0%)		3/102 (2.9%)		11/200 (5.5%)

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.