OP16 A randomised, multi-centre, double-blind, placebo-controlled study of a targeted release oral cyclosporine formulation in the treatment of mild-to-moderate ulcerative colitis: efficacy results

Abstract

Background: Cyclosporine (CsA) is an effective treatment for patients with acute severe ulcerative colitis (UC), and studies have shown that it has an impact on disease activity comparable to the anti-TNF agent, infliximab.1,2 Concerns regarding systemic toxicities have limited its role to short-term induction therapy and as a bridge to other therapies. ST-0529 is a novel low dose, controlled release formulation of CsA. A Phase 1 dose-ranging study demonstrated that tissue concentrations improved when it is given twice daily (BID).3 Methods: A total of 118 subjects with mild (baseline DAI < 6) or moderate (baseline DAI ≥ 6) UC were randomised 1:1 to receive 75 mg ST-0529 once daily or placebo (53 and 65 patients, respectively) for 4 weeks in a multi-centre, randomised, double-blind, placebo-controlled, Phase IIa study. Patients using UC medications (eg low-dose steroids, 5-aminosalicylates, and immunomodulatory agents) on screening could continue them if agreed to maintain a stable dosing regimen during the study. The primary objective was to evaluate the efficacy of ST-0529 in inducing clinical remission (DAI score ≤2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary objectives included clinical response, mucosal and histological healing, safety, and tolerability. Results: A numerical although not statistically significant advantage of ST-0529 over placebo was found for rates of clinical remission (ST-0529: 13.2%; placebo: 6.3%, p = 0.2211) and clinical response (ST-0529: 30.2%; placebo: 18.8%, p = 0.1923). There were no differences between the treatment groups for mucosal and histological healing. ST-0529 was safe and well-tolerated. A post hoc subgroup analysis was performed to evaluate effects by disease severity. Clinical remission and clinical response rates in subjects with moderate (baseline DAI ≥6) and mild (baseline DAI <6) disease (ITT, N = 118) Conclusions: In this pilot study, ST-0529 given once daily, was safe, well tolerated, and showed a numerically higher, but not statistically significant difference in remission rate in patients with mild-to-moderate UC compared with placebo after 4 weeks of treatment. In the post hoc analysis, differences in the clinical response between treatment subgroups achieved statistical significance in some subgroups, the largest clinical response rate in moderate UC patients taking 5-aminosalicylates and/or steroids. These preliminary data, added to the data from a Phase 1 study, support further development of ST-0529 as a treatment for the induction and maintenance of remission in UC patients with moderate to severe disease. (Table Presented).