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

Inclusion Criteria:

1. Male or female ≥ 18 years of age.
2. Well established diagnosis of moderate to moderately severe chronic active UC with aCAI score ≥9, an endoscopic score ≥2, not responding adequately to currently availabletherapies and potential candidates for colectomy. Previously tried therapies shouldinclude:

• At least one treatment course with mesalazine; at least 2.4 g/day for at least 4weeks, or at least one treatment course with similar drugs in this class.
• At least one full dose treatment course of corticosteroids (which can be thetreatment of a recent relapse), with up to 0.75 mg/kg as a starting dose orhighest dose according to local clinical practice.
• At least one treatment course of azathioprine or mercaptopurine of at least 3months duration and/or at least one adequate treatment course of an anti-TNFalpha.
• Any unsuccessful combination treatment of the above.
• May have tried treatment with cyclosporine and/or tacrolimus or any otherimmunosuppressant/immunomodulating agent.
• Intolerance to any of the above medications is judged as inadequate response.

3. Patients shall at study enrolment be on an accumulated stable tolerable GCS doseequivalent to at least 140 mg of prednisolone/prednisone (by any route ofadministration) for the last two weeks. Patients may also be on concomitant therapiessuch as, but not restricted to, 5-ASA, azathioprine and sulphasalazine.
4. Ability to understand the treatment, willingness to comply with all studyrequirements, and ability to provide informed consent.

Exclusion Criteria:

1. Patients with suspicion of Crohn's enterocolitis, ischaemic colitis, radiationcolitis, diverticular disease associated colitis, as well as microscopic colitisshould 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 compromisedstate as judged relevant by the investigator.
3. Patients with acute fulminant UC and/or signs of systemic toxicity to an extent thatrequires immediate surgical action.
4. History or presence of any colonic malignancy and/or dysplasia.
5. Concomitant treatment with cyclosporine, tacrolimus, anti-TNFs or similarimmunosuppressants/immunomodulators is not allowed and should have been discontinued 4weeks before enrolment. Patients who fail the wash-out criteria can undergo wash-outand be re-screened at a later time point. Ongoing treatment of anti-TNFs, tacrolimusor similar immunomodulators/immunosuppressant drugs should only be stopped in case ofdocumented lack of efficacy or in case of intolerable side effects.
6. Treatment with antibiotics or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) withintwo weeks before enrolment.
7. An active ongoing infection.
8. History of latent or active tuberculosis, evidence of prior or currently activetuberculosis by chest x-ray, patient with or having had frequent close contact withperson with active tuberculosis, patients who previously have tested positive for atuberculin skin test, or Mantoux (PPD) test, except in the case of previousvaccination or positive interferon gamma release test during screening or within 12weeks prior to randomisation.
9. Known history of HIV infection based on documented history with positive serology orHIV positive serology.
10. Previously documented positive hepatitis B surface antigen determination,determination of total antibodies to the hepatitis B capsid antigen and/or hepatitis Cantibody (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 (reliablemethods are barrier protection, hormonal contraception, intra-uterine device orabstinence) throughout the duration of the study (52 weeks).
15. Concurrent participation in another clinical study with investigational therapy orprevious use of investigational therapy within 30 days before enrolment. Patients whofail the wash-out criteria can undergo wash-out and be re-screened at a later timepoint.