The purpose of this study is to determine whether HuMax-CD4 is effective in the treatment of active RA in participants who have failed treatment with MTX and at least one TNF-alpha blocking agent.

This is a multi-center, double-blind, placebo-controlled, parallel-group, randomized trial of HuMax-CD4 in the treatment of participants with active RA who have failed treatment with MTX and at least one TNF-alpha blocking agent. Participants are randomized to receive one of two doses of HuMax-CD4 or placebo. The drug will be administered as a subcutaneous infusion (given just under the skin), more often in the beginning and then followed by a maintenance dose. There is a 4 week follow up period, and the final evaluation of the clinical endpoints takes place 26 weeks after treatment start. The trial lasts about 28 weeks in all.

Inclusion Criteria:

• A diagnosis of rheumatoid arthritis according to the American College of Rheumatology 1987 revised criteria (ACR) of at least 6 months duration.
• Active disease at the time of screening.
• Failure to tolerate MTX, or lack of efficacy after a minimum of 6 months treatment with MTX.

Exclusion Criteria:

• Active autoimmune disease requiring therapy (other than rheumatoid arthritis and secondary Sjögren's disease).
• Syndromes such as Fibromyalgia which require chronic pain treatment.
• Most past or current cancers.
• Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest, nasal or throat infections, tuberculosis, hepatitis B and C.
• History of infected joint prosthesis within 5 years.
• Most active medical conditions such as heart disease, kidney disease, liver disease, blood diseases, hormonal disturbances, lung disease, psychiatric disease.
• Drug or alcohol abuse.
• Pregnant or breast-feeding women may not participate. Women of childbearing potential must use either contraceptive pills or an intra-uterine device for the entire study period.

Note: Other protocol defined Inclusion and Exclusion criteria may apply.