HF2 Therapy in the Treatment of Active Ulcerative Colitis

1.1 Objective: To investigate the efficacy and safety of HF2 to induce remission in patients with active UC. 1.2 Methods: This will be a two-stage study: Stage 1 will comprise an open label single arm exploratory study of 10 active UC patients investigating HF2 therapy for induction of remission in outpatients with active UC. Stage 2: If clinical response is achieved in ≥ 3 patients and no significant safety signals will emerge, the investigators will proceed to a prospective pilot randomized placebo-controlled study. Stage 1: Open label study 1.7 Primary outcome stage I The primary outcome will be the percentage of patients in clinical remission (SCCAI score of ≤2) at week 4 after initiation of therapy Secondary outcomes (phase 1): 1.7.1 The percentage of patients who had a rapid clinical response at day 7 after induction of therapy 1.7.2 The percentage of patients who had a clinical response at week 4 after initiation of therapy 1.7.3 Improvement in endoscopic score at week 4 compared to baseline according to modified endoscopic Mayo score (improvement of ≥ 1 point) 1.7.4 Achievement of mucosal healing (endoscopic modified Mayo score of ≤1). 1.7.5 Percentage of patients who achieve normalization and/or \>50% improvement in C-reactive protein (CRP) and/or calprotectin levels (computed out of patients with abnormal values at baseline for these indices). 1.7.6 Time-to-response defined as number of days to achieve a drop of ≥3 points of the SCCAI score. 1.7.7. Time-to-ceasing of bleeding, defined as number of days for complete absence of blood in stools (SCCAI bleeding sub-score of 0), in those patients who has at least some blood in stool at entry (SCCAI bleeding sub-score of 1 or more). 1.7.8 The percentage of patients in clinical remission at day 7 after induction of therapy. 1.7.9. Improvement in IBD quality of life as gauged by questionnaire (IBDQ). 2 Intervention: Patients diagnosed with active UC will receive HF2 therapy for 4 weeks. 3 Procedures: 3.2 At inclusion: clinical and endoscopic assessment, blood and stool tests, cardiac echo and liver ultrasonography 3.4 clinical and endoscopic assessment, blood and stool tests, cardiac echo and liver ultrasonography Stage II: A multicenter randomized placebo controlled trial. The study will be performed in Sheba Medical Center and up to 2 additional European centers (TBD). For this stage of the trial , the patients will received HF2 combintation or similar (as described above) (2:1 allocation) for 8 weeks. After completion of 8 weeks, all responders previously on active drug will receive additional 8 weeks of oral curcumin or placebo as per original arm. Primary outcome: a composite outcome of clinical response (reduction in SCCAI of ≤3 OR achievement of clinical remiision defined as SCCAI ≤2) coupled with an objective evidence of response ( Mayo score improvement of ≥1 or 50% FcAL reduction ) at week 8 Secondary outcomes: * Percentage of patients in clinical remission (SCCAI≤2) at week 8 * The percentage of patients who had a clinical response at week 8 after initiation of therapy * Improvement in endoscopic score at week 8 compared to baseline according to endoscopic Mayo score (improvement of ≥ 1 point) * Achievement of mucosal healing (endoscopic modified Mayo score of ≤1) at week 8 * Percentage of patients who achieve normalization and/or \>50% improvement of CRP and/or calprotectin levels (computed out of patients with abnormal values at baseline for these indices) at week 8. * Percentage of patients in corticosteroid-free clinical remission at week 8 * Improvement in IBD quality of life as gauged by questionnaire (IBDQ). * Percentage of patients in clinical remission at week 16 * Percentage of patients with clinical response at week 16 * Percentage of patients with normalized fecal calprotectin and CRP 6.2. Intervention: Patients will be randomized into one of two arms: HF2 or placebo formulation (2:1 proportion) for 8 weeks. Following the first 8 weeks, responders w ill receive an additional 8 weeks of curcumin 1.5 g/d or placebo (as per original arm). Patients will undergo clinical, laboratory (CRP, biomarkers, blood chemistry, CBC\_biomarker (CRP and fecal calprotectin, at week 0,4,8 and 16 , and endoscopic assessment at baseline and week 8. Cardiac echo and liver US will be performed at week 0 and 8. Corticosteroid tapering will be allowed as per treating physician's discretion after week 8.