A Randomized, Double-blind, Placebo-controlled Study of a Controlled Release Minicapusle Formulation of Ciclosporin (CyCol™) in the Treatment of Ulcerative Colitis

INTERVENTION: Product Name: CyCol Product Code: CyCol Pharmaceutical Form: Modified‐release capsule, hard INN or Proposed INN: ciclosporin CAS Number: 59865‐13‐3 Current Sponsor code: ciclosporin Other descriptive name: cyclosporine (USAN) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Ulcerative colitis ; MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of CyCol (a controlled release minicapsule formaultion of ciclosporin) in inducing clinical remission, defined as a Disease Activity Index (DAI) score less than or equal to 2 after 4 weeks of treatment, in patients with mild to moderate ulcerative colitis (UC) involving at least the rectum and sigmoid colon, with no individual DAI sub‐score >1 at week 4. Patients in remission by this definition will have a rectal bleeding DAI sub‐score of either 0 or 1. Primary end point(s): Efficacy: clinical remission defined as DAI score of less than or equal to 2 at Week 4 with no‐individual DAI sub‐score > 1 at week 4. Patients in remission by this definition will have a rectal bleeding DAI sub‐score of either 0 or 1. Secondary Objective: To evaluate further the efficacy of CyCol in this subject population based on the following:; ‐ mucosal healing; ‐ reduction in DAI score of less than or equal to 3 and with a decrease in the rectal bleeding sub‐score of less than or equal to 1 or an absolute rectal bleeding sub‐score of 0 or 1.; ‐ histological healing; To evaluate safety and tolerability of CyCol in this subject population. INCLUSION CRITERIA: 1. Male and female subjects aged >18 years. 2. Subjects with a mild to moderate diagnosis of UC involving at least the rectum and sigmoid colon (i.e., ulcerative proctosigmoiditis, left‐sided ulcerative colitis or pancolitis), determined by historical (> 3 months prior to Day 0) colonoscopy or, sigmoidoscopy, with biopsies. 3. Clinical severity assessed at screening using the Disease Activity Index (DAI, Table 1) of 4 to 10, inclusive, and must be restricted to either mild or moderate UC defined as:‐ Mild clinical disease — Subjects with mild clinical UC often present insidiously with intermittent rectal bleeding associated with the passage of mucus, and mild diarrhoea with fewer than 4 small loose stools per day. Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease. ‐ Moderate clinical disease