Medarex, Inc (PRINCETON, New Jersey), a biopharmaceutical company focused on fully human antibody-based therapeutics to treat inflammation, autoimmune disorders, cancer, and infectious diseases, announced that it has initiated two phase II clinical development programs of MDX-1100, a fully human monoclonal antibody that targets CXCL10 (also known as IP-10), in ulcerative colitis (UC) and rheumatoid arthritis (RA).

Patients in the randomized, double-blind, placebo-controlled, international, multicenter study in UC will be administered four doses of MDX-1100 at 10 mg/kg or placebo every 2 weeks. The trial is expected to enroll 106 patients, all of whom will have active UC and will continue standard UC therapy during the trial. The primary endpoint will be response rate at 8 weeks based on the Mayo score, a composite endpoint that assesses stool frequency and the amount of bloody stool per day as recorded in a patient diary, on physician global assessment, and on the assessment of colon mucosal inflammation ascertained by endoscopy.

Patients in the randomized, double-blind, placebo-controlled, multicenter study in RA will be administered six doses of MDX-1100 at 10 mg/kg or placebo every 2 weeks. The trial is expected to enroll 70 patients at multiple sites in Europe. All patients will have active RA while on methotrexate, and the primary endpoint will be ACR20 response at 12 weeks.

Medarex reported positive safety data from two phase I trials supporting initiation of the two current trials. One open-label pilot study evaluated the safety (primary endpoint) and preliminary efficacy of escalating single doses of MDX-1100 in 11 patients with moderate-to-severe UC. The study demonstrated that single doses (0.3mg/kg-10 mg/kg) of MDX-1100 in patients were safe and well tolerated. Four patients in the study had protocol-defined clinical responses, determined by Ulcerative Colitis Disease Activity Index, physician global assessment, and the assessment of colon mucosal inflammation ascertained by endoscopy. None of the three serious adverse events reported in the study were considered drug related.

The other phase I double-blind, placebo-controlled study was conducted to determine safety and pharmacokinetics of escalating single doses (0.01 mg/kg-10 mg/kg) of MDX-1100 in 50 healthy volunteers. The agent demonstrated dose-proportional pharmacokinetics and a potential pharmacodynamic effect that signaled a decrease in the production of CXCL10 at the10 mg/kg dose. There were no infusion reactions, and the agent was nonimmunogenic. No serious adverse effects were observed; the most common drug related adverse events were drowsiness, cough, and shortness of breath.

MDX-1100 is a high-affinity, neutralizing, fully human IgG1k that targets CXCL10, a chemokine expressed in association with multiple inflammatory disease indications such as RA, inflammatory bowel disease, and multiple sclerosis. CXCL10 induces expression of several pro-inflammatory molecules and these CXCL10 inducible genes have so far found to be up-regulated in patients with UC.