The Efficacy and Safety of Cobitolimod (Kappaproct®) in Chronic Active Treatment Refractory Ulcerative Colitis Patients
Condition: Colitis, Ulcerative
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Cobitolimod; Placebo
Intervention description: 30 mg rectal dose at week 0 and 4; Rectal dose at week 0 and 4
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colitis, Ulcerative; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Immunomodulatory Therapy; Glucocorticoids; Anti-Inflammatory Agents; Therapeutic uses

Summary:

      The purpose of this study is to determine if cobitolimod (former called Kappaproct®) is
      effective in the treatment of chronic active ulcerative colitis patients not responding to
      available therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female ≥ 18 years of age.

          2. Well established diagnosis of moderate to moderately severe chronic active UC with a
             CAI score ≥9, an endoscopic score ≥2, not responding adequately to currently available
             therapies and potential candidates for colectomy. Previously tried therapies should
             include:

               -  At least one treatment course with mesalazine; at least 2.4 g/day for at least 4
                  weeks, or at least one treatment course with similar drugs in this class.

               -  At least one full dose treatment course of corticosteroids (which can be the
                  treatment of a recent relapse), with up to 0.75 mg/kg as a starting dose or
                  highest dose according to local clinical practice.

               -  At least one treatment course of azathioprine or mercaptopurine of at least 3
                  months duration and/or at least one adequate treatment course of an anti-TNF
                  alpha.

               -  Any unsuccessful combination treatment of the above.

               -  May have tried treatment with cyclosporine and/or tacrolimus or any other
                  immunosuppressant/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 dose
             equivalent to at least 140 mg of prednisolone/prednisone (by any route of
             administration) for the last two weeks. Patients may also be on concomitant therapies
             such as, but not restricted to, 5-ASA, azathioprine and sulphasalazine.

          4. Ability to understand the treatment, willingness to comply with all study
             requirements, and ability to provide informed consent.

        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.