Trubion Pharmaceuticals Inc (SEATTLE, Washington), a biopharmaceutical company creating protein therapeutic product candidates to treat autoimmune and inflammatory diseases and cancer, announced that its partner, Wyeth Pharmaceuticals, has commenced patient dosing in a multicenter, phase IIb clinical trial of TRU-015. The Small Modular ImmunoPharmaceutical (SMIP™) agent will be tested in patients with rheumatoid arthritis (RA). Previously reported data demonstrated TRU-015's ability to significantly improve RA signs and symptoms, and maintain response rates with repeat administration of single doses given every 6 months.

The randomized, parallel, double-blind, placebo-controlled, dose regimen-finding study will evaluate the safety and efficacy of two dosing regimens administered to ~216 patients with active, seropositive RA on a background of methotrexate (MTX). The study is designed to help identify an induction dosing regimen and to further establish the most effective treatment regimen for the agent. The primary outcome measurement will be the ACR50 response measured at week 24. Secondary efficacy measures at week 24 through week 52 include ACR20 and ACR50 responses, DAS28, MRI, cytokines, and B-cell subsets. Pharmacogenomic substudies will be performed and reported.

Five sites in the US are currently recruiting; patient inclusion criterion includes clinical diagnosis of active seropositive RA on a stable dose of MTX (7.5-25 mg/week) for at least 12 weeks with or without a history of anti-TNF use. Exclusion criterion includes prior use of rituximab or other B-cell depleting agents. The final data collection for the primary outcome measure is expected in June 2011.

TRU-015 is a novel single-chain polypeptide targeting CD20 (B-cell depleting) and is engineered for potent antibody dependent cellular cytotoxicity activity and attenuated complement dependent cytotoxicity activity. In addition to the ongoing development of the agent for RA, an IND has been filed for TRU-015 for systemic lupus erythematosus. Approximately one third to one half the size of conventional therapeutic monoclonal antibodies, SMIP drugs are engineered to possess the full binding and activity function of a monoclonal antibody and to exhibit selective target binding and long in vivo half-lives.