Genmab announced today the US Food and Drug Administration (FDA) accepted its Investigational New Drug Application (IND) to start a Phase I/II dose escalation trial for HuMax-CD20 to treat patients with active rheumatoid arthritis (RA) who have failed one treatment with one or more disease modifying anti-rheumatic drugs (DMARDs).
A total of 60 patients will be randomized into three cohorts each containing 20 patients. In each cohort 16 patients will receive two infusions of HuMax-CD20 (300, 700 or 1000 mg doses) and 4 patients will receive placebo given 14 days apart. All patients in the study will also receive methotrexate, a recognized treatment in the US for RA. Patients will be followed for 24 weeks to evaluate safety and efficacy and then every 12 weeks until B-cell counts return to baseline levels. Genmab plans to initiate the study during the early part of 2005.
HuMax-CD20 is a human antibody which is effective at binding to the disease target, and releases only very slowly from the target over time. In December 2004 Genmab presented positive data from a Phase I/II trial with patients with relapsed or refractory follicular lymphoma showing 55% of patients treated with HuMax(TM)-CD20 achieved a clinical response in the Phase I/II study, including two complete responses and one unconfirmed complete response for a 27% complete response rate. These responses were observed in 11 evaluable patients among the first 15 of the 40 patients included in this study at the week 11 evaluation point.
A Phase I/II trial to treat patients with Chronic Lymphocytic Leukemia is ongoing.
The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin.
Rheumatoid arthritis (RA) is a systemic inflammatory disease which affects 0.8-1.0% of all populations. The aetiology of RA remains unknown.