Chronic active treatment refractory ulcerative colitis MedDRA version: 14.1 Level: PT Classification code 10009900 Term: Colitis ulcerative System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Kappaproct
Pharmaceutical Form: Rectal solution
Current Sponsor code: DIMS0150
Other descriptive name: DIMS0150
Concentrat
Sponsors
InDex Pharmaceuticals AB
Eligibility
Sex/Gender
All
Inclusion 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 treatment course of corticosteroids (which can be the treatment of a recent relapse), with up to 0.75 mg/kg as 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 corresponds to 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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. 6. Treatment with antibiotics or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within two weeks before enrolment. 7. An active ongoing infection. 8. Positive Clostridium difficile stool assay. 9. Currently receiving parenteral nutrition or blood transfusions. 10. Pregnancy or breast-feeding. 11. 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 trial (52 weeks) 12. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the induction of clinical remission with Kappaproct given as an add-on treatment in two doses of 30 mg each compared to placebo. ; Secondary Objective: • To evaluate the rate of colectomy with Kappaproct given as an add-on treatment in two doses of 30 mg each compared to placebo. • To evaluate the induction and maintenance of steroid-free remission. • To evaluate safety and tolerability. ;Primary end point(s): The induction of clinical remission at week 12, defined as a CAI score of =4.;Timepoint(s) of evaluation of this end point: Refer to E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Refer to E.5.2; Secondary end point(s): - The time to colectomy. - The rate of colectomy at 3, 5 and 12 months. - Steroid free remission at 5 and 12 months. - The induction of clinical remission at week 12, defined as a CAI score of =4, with subscores of blood in stool and number of stools weekly not exceeding 0 and 0 or 1, respectively. - The induction of symptomatic remission at week 1, 4, 8 and 12, and the maintenance of this remission at 5 and 12 months, defined as subscores of blood in stool and number of stools weekly not exceeding 0 and 0 or 1, respectively. - The induction of registration remission at week 4 and 12, and the maintenance of this remission at 5 and 12 months, defined as a CAI score of =4 and an endoscopic score of 0 or 1. - The induction of clinical remission at week 1, 4, 8 and the maintenance of this remission at 5 and 12 months, defined as a CAI score of =4. - The induction of clinical response at week 1, 4, 8 and 12, defined as a decrease in CAI score of =5 from baseline. - Health related quality of life evaluation using an inflammatory bowel disease questionnaire (IBDQ) and a short-form health survey with 36 questions (SF-36) at week 12 and at 12 months, compared to baseline. - The induction of mucosal healing defined as an endoscopic score of 0 or 1 at week 4 • The histopathological response/remission at week 4 and 12. Histopathological response is defined as an improvement in the histopathological score of =3 from baseline, i.e. a histopathological response could go from 5 to 2 or from 4 to 1. Histopathologic | — |
Countries
Czech Republic, Germany, Hungary, Italy, Poland, United Kingdom
Contacts
Public ContactInDex Pharmaceuticals AB
InDex Pharmaceuticals AB
Outcome results
None listed