Intranasal administration of recombinant human cartilage glycoprotein-39. A phase I escalating cohort study in patients with rheumatoid arthritis

OBJECTIVE: To investigate safety and tolerability and pilot efficacy of repeated single doses of Org39141 in patients with active rheumatoid arthritis (RA). Org 39141 is recombinant human cartilage glycoprotein-39, intended to induce mucosal tolerance upon intranasal administration. METHODS: RA patients with moderate disease activity were treated for 4 weeks and followed for another 8 weeks. The trial had a sequential cohort design: RA patients in the first cohort received 4 intranasal doses (one per week) of either 25 microg Org 39141 or placebo; in subsequent cohorts, treatment with 125microg, 625 microg, or 3125 microg Org39141 was compared to placebo. Safety was evaluated by means of reporting adverse events, standard laboratory testing, and nose examination. The primary efficacy endpoint was RA disease activity as measured by the Disease Activity Score 28 (DAS28). RESULTS: A total of 36 patients were randomized. Org39141 was well tolerated, and no severe or serious adverse events (AE) were reported. In the pooled placebo group, a decrease in DAS28 was observed, but to a lesser extent than in the Org 39141 treatment groups. After 4 weeks of treatment, the mean decrease in DAS in the 625 microg Org 39141 treatment group (-24%) was statistically (p = 0.02) and clinically (EULAR criteria) significantly larger than in the pooled placebo group (-3%). Once-weekly intranasal treatment with Org39141 was well tolerated, and no serious or severe AE were reported. A trend towards efficacy was observed. Our results are encouraging for further clinical development of Org39141.