The Efficacy and Safety of Cobitolimod (Kappaproct®) in Chronic Active Treatment Refractory Ulcerative Colitis Patients

Exclusion Criteria

• •1. Patients with suspicion of Crohn's enterocolitis, ischaemic colitis, radiation colitis, diverticular disease associated colitis, as well as microscopic colitis should be excluded. Patients with disease limited to the rectum (ulcerative proctitis) should also be excluded.
• •2. History or presence of a clinically significant cardiovascular, hepatic, renal, haematological, endocrine, neurological, psychiatric disease, or immune compromised state as judged relevant by the investigator.
• •3. Patients with acute fulminant UC and/or signs of systemic toxicity to an extent that requires immediate surgical action.
• •4. History or presence of any colonic malignancy and/or dysplasia.
• •5. Concomitant treatment with cyclosporine, tacrolimus, anti-TNFs or similar immunosuppressants/immunomodulators is not allowed and should have been discontinued 4 weeks before enrolment. Patients who fail the wash-out criteria can undergo wash-out and be re-screened at a later time point. Ongoing treatment of anti-TNFs, tacrolimus or similar immunomodulators/immunosuppressant drugs should only be stopped in case of documented lack of efficacy or in case of intolerable side effects.
• •6. Treatment with antibiotics or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within two weeks before enrolment.
• •7. An active ongoing infection.
• •8. History of latent or active tuberculosis, evidence of prior or currently active tuberculosis by chest x-ray, patient with or having had frequent close contact with person with active tuberculosis, patients who previously have tested positive for a tuberculin skin test, or Mantoux (PPD) test, except in the case of previous vaccination or positive interferon gamma release test during screening or within 12 weeks prior to randomisation.
• •9. Known history of HIV infection based on documented history with positive serology or HIV positive serology.
• •10. Previously documented positive hepatitis B surface antigen determination, determination of total antibodies to the hepatitis B capsid antigen and/or hepatitis C antibody (HCVAb) with confirmation using the ribonucleic acid of hepatitis B virus.
• •11. Positive Clostridium difficile stool assay.
• •12. Currently receiving parenteral nutrition or blood transfusions.
• •13. Pregnancy or breast-feeding.
• •14. Women of childbearing potential not using reliable contraceptive methods (reliable methods are barrier protection, hormonal contraception, intra-uterine device or abstinence) throughout the duration of the study (52 weeks).
• •15. Concurrent participation in another clinical study with investigational therapy or previous use of investigational therapy within 30 days before enrolment. Patients who fail the wash-out criteria can undergo wash-out and be re-screened at a later time point.