A Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00445432

Enrollment

Registered

2007-03-09

Start date

2007-03-31

Completion date

2010-11-30

Last updated

2012-02-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease

Brief summary

To demonstrate the efficacy and safety of adalimumab for the maintenance of clinical remission in Japanese subjects with Crohn's disease.

Detailed description

This was a Phase 2/3, multicenter, randomized, double-blind (DB), placebo-controlled, two-arm, efficacy, safety, and pharmacokinetic study designed to demonstrate the effectiveness of adalimumab in Japanese patients with moderate to severe Crohn's Disease (CD). All participants who had completed Study M04-729 (NCT00445939), the lead-in adalimumab induction therapy study, were eligible for this study. Participants who rolled over into this study received either DB treatment (adalimumab or placebo) or open-label (OL) treatment with adalimumab. Crohn's Disease Activity Index (CDAI) was used to determine participants who were responders and participants who were in clinical remission. CDAI documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. It yields a total score \>= 0 and without upper limit. Baseline scores in the study ranged from 221 to 448. Low score=less severe CD activity. Decrease in score indicates improvement. Clinical remission is a CDAI score \< 150. Clinical response-70 (CR-70) = decrease in CDAI ≥ 70 points from lead-in study Baseline score. Clinical response-100 (CR-100) = decrease in CDAI ≥ 100 points from lead-in study Baseline score. Participants who had CR-70 response at Week 4 of the induction study were randomized into 1 of 2 treatment groups (double-blind adalimumab 40 mg every other week or adalimumab placebo every other week) using 2 stratification factors - CDAI category (CDAI less than 150 and CDAI 150 or higher) and presence/absence of fistula at Week 0 of this study. The double-blind treatment was to last from Week 0 to Week 52. Any time at or after Week 4 of this study, if a participant's disease flared (defined as a recurrence of very active disease, specifically an increase in CDAI when compared to Week 0 in this study of ≥ 70 points and a CDAI above 220) during the double-blind treatment period, the participant was allowed to move to OL treatment. At Week 52, all participants still receiving DB treatment were to be moved to open-label treatment and could continue in the study until adalimumab is approved for commercial use in Japan. Participants who did not respond by Week 4 in the induction study and participants who had disease flare during DB treatment of this study entered OL treatment and received adalimumab 40 mg every other week. At or after Week 4 of this study, if a participant in the open-label treatment group had a disease flare or if the participant was still not responding to treatment, the participant was allowed to dose escalate to adalimumab 80 mg every other week. Participants who entered open-label treatment were to be allowed to continue on open-label adalimumab until adalimumab is approved for commercial use in Japan. The study is complete. Results of this study are reported for endpoints at Week 52 (end of the DB treatment period) for subjects who received DB treatment (adalimumab or placebo) or OL adalimumab treatment and for endpoints at Week 148 for all subjects who received at least one dose of adalimumab in this study.

Interventions

BIOLOGICALadalimumab

Subcutaneous injection of 40 mg adalimumab (0.8 mL/injection) every other week (eow)

OTHERPlacebo

Subcutaneous injection of placebo (0.8 mL/injection) every other week (eow)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

15 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Subjects who successfully enrolled in and completed the M04-729, (NCT00445939) study

Exclusion criteria

* Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment	Week 52 of double-blind treatment	Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) \<150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is \>= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.

Secondary

Measure	Time frame	Description
Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	Week 52 of double-blind treatment	Crohn's Disease Activity Index (CDAI) documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	Week 52 of double-blind treatment	Crohn's Disease Activity Index (CDAI) documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	Crohn's Disease Activity Index (CDAI) is a measure of disease severity. Number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment	Week 52 of open-label treatment	Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) \<150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score is an indicator of the activity of Crohn's disease. It measures absence (score of 0) or presence (score of 1) of abdominal pain, diarrhea or bloody stools more than 6 times per day, anal lesion, anal fistula, other complication, abdominal mass, weight loss, fever above 38 degrees Centigrade, abdominal tenderness, and blood pigment below 10 g/dL. Total possible score=0 to 10; low score=less disease activity. Decrease in score indicates alleviation of the disease; increase indicates aggravation of disease.
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period. It has 32 questions about bowel function and related symptoms, and their social and emotional impact. For each item, participants select 1 of 7 responses. 1=poor quality of life (e.g., feeling of fatigue all of the time) and 7=good quality (e.g., feeling of fatigue none of the time). Scoring range = 32 to 224. Higher scores indicate better quality of life; increases in IBDQ = improved overall quality of life.
Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain, and rating of one's health. Score on the physical component ranges from 0 (Poorest Health) to 100 (Best Health).
Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment	The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation. The mental component reflects energy/vitality, social functioning, limitations, and ratings of one's mental health. Score on mental component ranges from 0 (worst score) to 100 (best score).

Other

Measure	Time frame	Description
Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 148	Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	Crohn's Disease Activity Index (CDAI) documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 148	Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	Crohn's Disease Activity Index (CDAI) documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 148	Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	Crohn's Disease Activity Index (CDAI) is a measure of disease severity. Number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/apthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI has a total score \>=0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.
Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 148	Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score is an indicator of the activity of Crohn's disease. It measures absence (score of 0) or presence (score of 1) of abdominal pain, diarrhea or bloody stools more than 6 times per day, anal lesion, anal fistula, other complication, abdominal mass, weight loss, fever above 38 degrees Centigrade, abdominal tenderness, and blood pigment below 10 g/dL. Total possible score=0 to 10; low score=less disease activity. Decrease in score indicates alleviation of the disease; increase indicates aggravation of disease.
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 148	Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period with 32 questions about bowel function and related symptoms & their social/emotional impact. Per item, participants select 1 of 7 responses (1=poor quality of life \[e.g., feeling of fatigue all of the time\]; 7=good quality \[e.g., feeling of fatigue none of the time\]). Scoring range=32 to 224. Higher scores indicate better quality of life; increases in IBDQ=improved overall quality of life.
Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148	Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	The Short Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain, and rating of one's health. Score on the physical component ranges from 0 to 100, with 0=Poorest Health and 100=Best Health.
Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148	Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	The Short Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 indicates alleviation of the disease and a decrease in score indicates aggravation. The mental component reflects energy/vitality, social functioning, limitations, and ratings of one's mental health. Score on mental component ranges from 0 (worst score) to 100 (best score).
Number of Participants Who Had Clinical Remission at Week 148	Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)	Clinical remission = Crohn's Disease (CD) Activity Index (CDAI) \<150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is \>= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
DB Adalimumab 40 mg Eow Double-blind adalimumab 40 mg every other week	25
Placebo Eow Double-blind adalimumab placebo every other week	25
OL Adalimumab 40 mg Eow Open-label adalimumab 40 mg every other week	32
Total	82

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
148 Weeks of Adalimumab Treatment	Adverse Event	0	0	0	32
148 Weeks of Adalimumab Treatment	Other	0	0	0	9
148 Weeks of Adalimumab Treatment	Withdrawal by Subject	0	0	0	3
Through Week 52 of NCT00445432 (M06-837)	Adverse Event	1	2	7	0
Through Week 52 of NCT00445432 (M06-837)	Moved to open-label	14	20	0	0
Through Week 52 of NCT00445432 (M06-837)	Other	0	1	2	0
Through Week 52 of NCT00445432 (M06-837)	Withdrawal by Subject	0	0	2	0

Baseline characteristics

Characteristic	Placebo Eow	OL Adalimumab 40 mg Eow	DB Adalimumab 40 mg Eow	Total
Age, Categorical <=18 years	2 Participants	3 Participants	0 Participants	5 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	23 Participants	29 Participants	25 Participants	77 Participants
Age Continuous	30.80 years STANDARD_DEVIATION 10.939	30.75 years STANDARD_DEVIATION 8.359	31.60 years STANDARD_DEVIATION 7.171	31.02 years STANDARD_DEVIATION 8.808
Region of Enrollment Japan	25 participants	32 participants	25 participants	82 participants
Sex: Female, Male Female	10 Participants	14 Participants	9 Participants	33 Participants
Sex: Female, Male Male	15 Participants	18 Participants	16 Participants	49 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	17 / 25	13 / 25	28 / 32	73 / 79
serious Total, serious adverse events	2 / 25	6 / 25	13 / 32	49 / 79

Outcome results

Primary

Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment

Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) \<150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is \>= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.

Time frame: Week 52 of double-blind treatment

Population: Modified Full Analysis Set (mFAS), defined as participants who had received adalimumab (not placebo) during the adalimumab induction study and who received at least 1 dose of DB study drug during this study. Nonresponder imputation (NRI) (clinical remission not achieved) was used for missing data.

Arm	Measure	Value (NUMBER)
DB Adalimumab 40 mg Eow	Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment	8 Participants
Placebo Eow	Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment	2 Participants

Secondary

Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

Crohn's Disease Activity Index (CDAI) is a measure of disease severity. Number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Time frame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment

Population: modified Full Analysis Set (mFAS), defined as participants who had received adalimumab (not placebo) during the adalimumab induction study and who received at least 1 dose of DB study drug during this study. Last observation carried forward (LOCF) used for missing data.

Arm	Measure	Value (MEAN)	Dispersion
DB Adalimumab 40 mg Eow	Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	-83.7 units on a scale	Standard Deviation 110.26
Placebo Eow	Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	-9.1 units on a scale	Standard Deviation 110.41

Secondary

Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period. It has 32 questions about bowel function and related symptoms, and their social and emotional impact. For each item, participants select 1 of 7 responses. 1=poor quality of life (e.g., feeling of fatigue all of the time) and 7=good quality (e.g., feeling of fatigue none of the time). Scoring range = 32 to 224. Higher scores indicate better quality of life; increases in IBDQ = improved overall quality of life.

Time frame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment

Population: Modified Full Analysis Set (mFAS), defined as participants who had received adalimumab (not placebo) during the adalimumab induction study and who received at least 1 dose of DB study drug during this study. Last observation carried forward (LOCF) used for missing data.

Arm	Measure	Value (MEAN)	Dispersion
DB Adalimumab 40 mg Eow	Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	27.8 units on a scale	Standard Deviation 32.44
Placebo Eow	Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	1.8 units on a scale	Standard Deviation 35.42

Secondary

Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score is an indicator of the activity of Crohn's disease. It measures absence (score of 0) or presence (score of 1) of abdominal pain, diarrhea or bloody stools more than 6 times per day, anal lesion, anal fistula, other complication, abdominal mass, weight loss, fever above 38 degrees Centigrade, abdominal tenderness, and blood pigment below 10 g/dL. Total possible score=0 to 10; low score=less disease activity. Decrease in score indicates alleviation of the disease; increase indicates aggravation of disease.

Time frame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment

Population: Modified Full Analysis Set (mFAS), defined as participants who had received adalimumab (not placebo) during the adalimumab induction study and who received at least 1 dose of DB study drug during this study. Last observation carried forward (LOCF) used for missing data.

Arm	Measure	Value (MEAN)	Dispersion
DB Adalimumab 40 mg Eow	Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	-0.8 units on a scale	Standard Deviation 1.89
Placebo Eow	Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	-0.2 units on a scale	Standard Deviation 1.34

Secondary

Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation. The mental component reflects energy/vitality, social functioning, limitations, and ratings of one's mental health. Score on mental component ranges from 0 (worst score) to 100 (best score).

Time frame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment

Population: Modified Full Analysis Set (mFAS), defined as participants who had received adalimumab (not placebo) during the adalimumab induction study and who received at least 1 dose of DB study drug during this study. Last observation carried forward (LOCF) used for missing data.

Arm	Measure	Value (MEAN)	Dispersion
DB Adalimumab 40 mg Eow	Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	9.6 units on a scale	Standard Deviation 8.37
Placebo Eow	Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	0.3 units on a scale	Standard Deviation 14.15

Secondary

Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain, and rating of one's health. Score on the physical component ranges from 0 (Poorest Health) to 100 (Best Health).

Time frame: Baseline of lead-in study (NCT00445939) to Week 52 of double-blind treatment

Population: Modified Full Analysis Set (mFAS), defined as participants who had received adalimumab (not placebo) during the adalimumab induction study and who received at least 1 dose of DB study drug during this study. Last observation carried forward (LOCF) used for missing data.

Arm	Measure	Value (MEAN)	Dispersion
DB Adalimumab 40 mg Eow	Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	4.4 units on a scale	Standard Deviation 9.09
Placebo Eow	Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment	0.2 units on a scale	Standard Deviation 6.31

Secondary

Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment

Time frame: Week 52 of open-label treatment

Population: OL efficacy set (assigned to OL treatment at Week 0, received \>= 1 dose of OL study drug). Last observation carried forward (LOCF) used for missing data.

Arm	Measure	Value (NUMBER)
DB Adalimumab 40 mg Eow	Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment	5 Participants

Secondary

Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment

Crohn's Disease Activity Index (CDAI) documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. CDAI has a total score \>= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Time frame: Week 52 of double-blind treatment

Population: OL efficacy set (assigned to OL treatment at Week 0, received \>= 1 dose of OL study drug) and mFAS (participants who had received adalimumab (not placebo) during adalimumab induction study and who received \>= 1 dose of DB study drug during this study). NRI (CR-100 not achieved) used for missing data for DB treatments; LOCF for OL treatment.

Arm	Measure	Value (NUMBER)
DB Adalimumab 40 mg Eow	Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	8 Participants
Placebo Eow	Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	2 Participants
OL Adalimumab 40 mg Eow	Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	8 Participants

Secondary

Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment

Time frame: Week 52 of double-blind treatment

Population: OL efficacy set (assigned to OL treatment at Week 0, received \>= 1 dose of OL study drug) and mFAS (participants who had received adalimumab \[not placebo\] during adalimumab induction study and who received \>= 1 dose of DB study drug during this study). Nonresponder imputation (NRI) (CR-70 not achieved) used for DB treatments; LOCF for OL treatment.

Arm	Measure	Value (NUMBER)
DB Adalimumab 40 mg Eow	Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	9 Participants
Placebo Eow	Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	2 Participants
OL Adalimumab 40 mg Eow	Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment	10 Participants

Other Pre-specified

Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 148

Crohn's Disease Activity Index (CDAI) is a measure of disease severity. Number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/apthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI has a total score \>=0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Time frame: Baseline of lead-in study (NCT00445939) to Week 148 relative to the first dose of adalimumab in NCT00445432 (Study M06-837)