A Study to Assess the Safety and Efficacy of Adalimumab When Added to Inadequate Standard Anti-Rheumatic Therapy in Patients With Active Rheumatoid Arthritis

Study Overview
=================
Brief Summary
-----------------
This is an open-label, multi-center study in which adalimumab (D2E7) is administered subcutaneously 40 mg every other week in addition to current anti-rheumatic therapies. Patients must have active disease despite standard anti-rheumatic therapy.

Official Title
-----------------
An Open-Label, Multi-Center Study to Assess the Safety and Efficacy of the Fully Human Anti-TNF-α Monoclonal Antibody Adalimumab (D2E7) When Added to Inadequate Standard Anti-Rheumatic Therapy in Patients With Active Rheumatoid Arthritis

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Biological: adalimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be 18 years or older ACR criteria for diagnosis of RA for at least 3 months. Active RA as defined by DAS28 >= 3.2 at study entry. Unsatisfactory response or intolerance to prior DMARDs. A negative pregnancy test (serum HCG) for women of childbearing potential prior to start of study treatment. Use of reliable method of contraception e.g. IUDs, condoms, or hormone (oral, implantable, or injectable) contraceptives by all female patients of childbearing potential. Male patients with procreative capacity should also ensure that effective contraception is used during the study and for 70 days after study completion Exclusion Criteria: Prior treatment with alkylating agents such as cyclophosphamide or chlorambucil. Prior treatment with intravenous immunoglobulin or any investigational agent within 30 days, or 5 half lives of the product, whichever is longer. Prior treatment with investigational biologic therapy (e.g. anti CD4) Treatment within the last 2 months with approved biologic therapy (eg etanercept, infliximab, anakinra) Prior treatment with total lymphoid irradiation History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma. History of or current acute inflammatory joint disease of origin other than RA, e.g. mixed connective tissue disease, systemic lupus erythematosus etc. History of uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, recent stroke (within 3 months) and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the protocol. Positive serology for hepatitis B or C indicating active infection History of positive HIV status. Persistent infection, or severe infections requiring hospitalization or treatment with iv antibiotics within 30 days, or oral antibiotics within 14 days prior to enrollment. Female subjects who are pregnant or breast-feeding. History of clinically significant drug or alcohol abuse in the last year. Previous diagnosis or signs of demyelinating diseases History of active tuberculosis (TB), histoplasmosis or listeriosis. Signs of previous TB infection (chest X-ray signs or positive PPD skin test). The diagnosis of previous TB infection will be based on chest X-ray signs and on PPD skin test.

Ages Eligible for Study
-----------------
Minimum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Open-label adalimumab | Biological: adalimumab<br>* 40mg every other week<br>* Other names: Humira;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of disease activity score (DAS28) compared with study entry |  | Week 12 | 
| EULAR and ACR response criteria at week 12 |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | Baseline - Week 12 | 
| Clinical laboratory parameters |  | Screening, Week 6 & Week 12 and/or ET |