Su1414 Efficacy and Safety of Sequential Rescue Treatments in Steroid Refractory Ulcerative Colitis Experience

Abstract

BACKGROUND AND AIM: A platform of new immunotherapeutic treatments called Site Specific Immunomodulators (SSIs) are being developed with the aim of reversing the chronic inflammation underlying cancer and some autoimmune diseases, including Crohn's disease. SSIs are novel complex biologics, each derived from a single species of fully inactivated pathogenic bacteria. The aim of the study was to observe the safety and potential therapeutic benefit of QBECO SSI in subjects with moderately to severely active Crohn's disease (CD). METHODS: Nine CD subjects between 24 and 44 years of age with active CD refractory to conventional therapy received QBECO SSI according to a compassionate use protocol. Subjects were taught to self-administer between 0.05 and 0.2 mL (median dose = 0.1 mL) of study treatment subcutaneously every second day, for a treatment duration of a minimum of 3 months, and a maximum of 11 months. Dose, dose frequency and side-effects were captured daily in a subject diary, and subjects were followed closely by a physician who regularly assessed their adverse events and clinical symptoms of CD. Ethical approval and informed written consent were obtained. RESULTS: Seven of the 9 subjects reported full resolution of clinical symptoms with a course of QBECO SSI treatment of three months or more. Four of these subjects had sustained clinical remission after discontinuing all medications including SSI treatment. The longest case of clinical remission reported is still ongoing, after more than 3.5 years. Three of the 6 subjects reporting full remission had follow-up colonoscopies or CT scan with confirmation of remission of CD. With a maximum followup period of over 36 months, no treatment-related serious adverse events have been reported to date. The only reported treatment-related adverse events associated with study treatment have been transient fever in three patients which resolved without required treatment within 12 18 hours and a larger than anticipated transient local skin immune response to initial treatment dose, which was corrected with appropriate subsequent dose reduction. CONCLUSION: Based on these initial findings with the use of site specific immunomodulation in a compassionate use cohort of 9 subjects with active CD, QBECO SSI therapy appears to be safe and efficacious. QBECO SSI therapy is now being evaluated through a phase 1/ 2 randomized, placebo-controlled, double-blind clinical trial to further understand its benefit/ risk profile.