Long-term Safety and Tolerability Study of Adalimumab in Subjects With Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
To evaluate the long-term maintenance of response, safety and tolerability of repeated administration of adalimumab in subjects with Crohn's disease who participated in and successfully completed Protocol M02-404 or Protocol M04-691.

Official Title
-----------------
A Multi Center, Open Label Study of the Human Anti TNF Monoclonal Antibody Adalimumab to Evaluate the Long Term Safety and Tolerability of Repeated Administration of Adalimumab in Subjects With Crohn's Disease

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Biological: Adalimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must have successfully completed either the M02-404 (NCT00077779) or M04-691 (NCT00105300) protocol to be eligible for this study Diagnosis of Crohn's disease Willing and able to give informed consent Exclusion Criteria: Diagnosis of ulcerative colitis Women cannot be pregnant or breastfeeding Previous history of listeria infection or untreated tuberculosis Previous history of cancer other than successfully treated skin cancer or carcinoma-in-situ of the cervix

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Adalimumab|Adalimumab 40 mg by subcutaneous injection every other week or every week|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Clinical Remission | Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 156 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Clinical Remission | Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 48 | 
| Percentage of Subjects Achieving Clinical Remission | Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 108 | 
| Percentage of Subjects Achieving Clinical Remission | Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 204 | 
| Percentage of Subjects Achieving Clinical Response 100 (CR-100) | A CR-100 is a decrease from baseline in CDAI score of 100 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 156 | 
| Percentage of Subjects Achieving Clinical Response 70 (CR-70) | A CR-70 is a decrease from baseline in CDAI score of 70 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 156 | 
| Percentage of Subjects Achieving Steroid-free Clinical Remission | Steroid-free remission was achieved if the subject stopped taking steroids before the visit and had a Crohn's Disease Activity Index (CDAI) score of <150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 156 | 
| Percentage of Subjects Achieving Steroid-free CR-100 | Steroid-free CR-100 was achieved if the subject stopped taking steroids before the visit and had a decrease from baseline in CDAI score of 100 or more points at that visit. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. | Week 156 | 
| Percentage of Subjects With Fistula Remission | Fistula remission was defined as the absence of draining fistulas in subjects with fistula present at the preceding study's baseline visit. | Week 156 | 
| Percentage of Subjects With Infection |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Serious Infection | Serious infections are infectious adverse events that meet at least one criterion for a serious adverse event (e.g., death, life threatening event, hospitalization) including tuberculosis (TB), bacterial sepsis, invasive fungal infections (e.g., histoplasmosis), and infections due to other opportunistic pathogens. | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Malignancy |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Lymphoma |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Nonmelanoma Skin Cancer |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Malignancy (Excluding Nonmelanoma Skin Cancer and Lymphoma) |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Malignancy (Including Lymphoma, Excluding Nonmelanoma Skin Cancer) |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Injection Site Reaction-related Adverse Event | An injection site reaction is any adverse event corresponding to a preferred term beginning with injection site excluding injection site arthritis, injection site movement impairment, injection site photosensitivity, injection site joint effusion, injection site joint inflammation, injection site scab, injection site joint pain, or injection site laceration. | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Opportunistic Infection (Excluding Tuberculosis) |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Congestive Heart Failure |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Demyelinating Disease |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Hepatic-related Adverse Event |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Allergic Reaction-related Adverse Event |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Lupus-like Syndrome |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Hematologic-related Adverse Event |  | Up to 262 weeks of adalimumab treatment | 
| Percentage of Subjects With Fatal Adverse Event |  | Up to 262 weeks of adalimumab treatment |