The Efficacy and Safety of Kappaproct in Chronic Active Treatment Refractory Ulcerative Colitis Patients (COLLECT)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Placebo-controlled, Double-blind, Randomised Study to Assess the Efficacy and Safety of Kappaproct as an add-on to Current Practice in Chronic Active Treatment Refractory Ulcerative Colitis Patients|
- Clinical remission [ Time Frame: Week 12 ]Proportion of participants with induction of clinical remission at week 12, defined as a CAI score of ≤4.
- The time to colectomy [ Time Frame: Within 12 months ]Median time to colectomy after 1st dose.
- The rate of colectomy [ Time Frame: 3, 5 and 12 months ]Proportion of participants undergoing colectomy 3, 5 and 12 months after 1st dose.
- Steroid free remission at 5 and 12 months [ Time Frame: 5 and 12 months ]Proportion of participants with steroid free remission at 5 and 12 months after 1st dose.
- Health related quality of life evaluation [ Time Frame: Week 12 and 52 ]Mean change from baseline to week 12 and 52 in the sum score of the inflammatory bowel disease questionnaire (IBDQ) and the SF-36 scales.
- The induction of mucosal healing [ Time Frame: Week 4 and 12 ]Proportion of participants with induction of mucosal healing, defined as an endoscopic score of 0 or 1, at week 4 and 12.
- Frequency and duration of UC relapses [ Time Frame: During 12 months ]Proportion of UC relapses and the duration of these, defined as an increase of CAI ≥5 from the last study visit.
- The induction of symptomatic remission [ Time Frame: Week 1, 4, 8 and 12 ]Proportion of participants with induction of symptomatic remission, defined as subscores of blood in stool and number of stools weekly not exceeding 0 and 0 or 1, respectively, at week 1, 4, 8 and 12.
- The induction of registration remission [ Time Frame: Week 4 and 12 ]Proportion of participants with induction of registration remission, defined as a CAI score of ≤4 and an endoscopic score of 0 or 1, at week 4 and 12.
|Study Start Date:||December 2011|
|Study Completion Date:||March 2014|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
2 doses 4 weeks apart
30 mg rectal dose at week 0 and 4
Other Name: DIMS0150
Placebo Comparator: Placebo
2 doses 4 weeks apart
Rectal dose at week 0 and 4
The study is a placebo-controlled, double-blind, randomised study to assess the efficacy and safety of Kappaproct as an add-on to current practice in treatment refractory ulcerative colitis patients. The study population will be chronic active ulcerative colitis patients who are no longer responding adequately to standard therapies and who are potential candidates for colectomy. Kappaproct/placebo will be add-on treatment allowing all included patients to be on concomitant medication, as well as mandatory steroids at inclusion, throughout the study.
Kappaproct (DIMS0150) is a modified single strand DNA-based synthetic oligodeoxyribonucleotide of 19 bases in length. The drug functions as an immunomodulatory agent by targeting the Toll-like receptor 9 (TLR9) present in immune cells (i.e., B-cells and pDCs) residing in high abundance on mucosal surfaces, such as colonic and nasal mucosa. The mucosa of the colon and rectum of patients with ulcerative colitis contains active immune cells, which produce damage to the tissue. The activation of these cells by Kappaproct results in the systemic release of specific cytokines (e.g., IL-10 and type I interferons) and chemokines which are believed to be important factors for the clinical effect of Kappaproct. Ex vivo experiments with Kappaproct have demonstrated that the drug has the ability to enhance the steroid sensitivity of peripheral blood mononuclear cells (PBMCs) obtained from steroid refractory UC patients. Thus, the desired effect is to restore steroid sensitivity in steroid refractory patients such that they may benefit from the anti-inflammatory actions of the steroid and ultimately become steroid free.
120 eligible patients will be randomly assigned in a 2:1 allocation to receive two single rectal doses of Kappaproct at 30 mg each, or placebo, at week 0 and 4.
The primary endpoint is the induction of clinical remission at week 12 and patients will be continuously followed for efficacy and safety until 12 months after the first dose. Secondary endpoints include the induction of symptomatic remission (number of stools and blood in stools), induction of registration remission (clinical and endoscopic remission) and rate of colectomy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01493960
Show 39 Study Locations
|Principal Investigator:||Christopher Hawkey, MD||Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK|