Based on guidance from the FDA and EMA, the phase III program for cobitolimod will consist of two sequential induction studies and a yearlong maintenance study with patients that have responded to cobitolimod as induction therapy. The phase III program will form the basis for marketing approval by confirming cobitolimod’s overall efficacy and safety profile in a large enough group of patients with moderate to severe, left-sided ulcerative colitis with an inadequate response or failure to tolerate conventional therapy, biological therapy or JAK inhibitors. The important initial CONCLUDE study is a randomised, double-blind, placebo-controlled induction study that will include approximately 440 patients. The primary endpoint will be clinical remission at week 6, which is the same primary endpoint as used in the successful phase IIb study CONDUCT. Apart from the dosing 250 mg given at baseline and week 3, which was the highest dose and the one that showed the best efficacy in the phase IIb study, the phase III study will also evaluate a higher dose, 500 mg, in an adaptive study design. Patients responding to cobitolimod in the induction study will be eligible to continue in the one-year maintenance study, where they will be treated with either cobitolimod or placebo once every three weeks.
Both the FDA and EMA endorsed the advancement of cobitolimod into phase III studies in patients with moderate to severe left-sided ulcerative colitis. The regulatory feedback allowed for flexibility in the design of the phase III program, for example, to conduct the induction studies sequentially and to include a higher dose in addition to the highest dose regimen tested in the phase IIb study (2×250 mg).
No, the interim analysis in the adaptive design will be blinded to InDex and will serve to select the best dose of the two doses included in the study, 250 and 500 mg. Safety will be monitored continuously in the study to confirm that there are no safety issues hindering the continuation of the study.
The study’s primary objective is to evaluate the efficacy of cobitolimod treatment compared to placebo in inducing clinical remission in patients with left-sided moderate to severe active ulcerative colitis. A blinded interim analysis will be performed to select the best dose out of 250 mg and 500 mg, which will be the dose used for the remaining phase III development.
The PK study will be conducted in parallel with the CONCLUDE study. The PK study will evaluate the systemic uptake of cobitolimod in local treatment of colonic inflammation. The study will include at least 6 patients with moderate to severe ulcerative colitis treated with doses of 500 mg of cobitolimod administered rectally.