The Efficacy and Safety of Kappaproct in Chronic Active Treatment Refractory Ulcerative Colitis Patients (COLLECT)
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Purpose
The purpose of this study is to determine if Kappaproct is effective in the treatment of chronic active ulcerative colitis patients not responding to available therapy.
| Condition | Intervention | Phase |
|---|---|---|
|
Colitis, Ulcerative |
Drug: Kappaproct Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Median time to colectomy after 1st dose.
- The rate of colectomy [ Time Frame: 3, 5 and 12 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Proportion of UC relapses and the duration of these, defined as an increase of CAI ≥5 from the last study visit.
| Estimated Enrollment: | 120 |
| Study Start Date: | December 2011 |
| Estimated Study Completion Date: | March 2014 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Kappaproct
2 doses 4 weeks apart
|
Drug: Kappaproct
30 mg rectal dose at week 0 and 4
Other Name: DIMS0150
|
|
Placebo Comparator: Placebo
2 doses 4 weeks apart
|
Drug: Placebo
Rectal dose at week 0 and 4
|
Detailed Description:
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 rectal doses of Kappaproct at 30 mg, 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female ≥ 18 years of age.
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.
- 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.
- Ability to understand the treatment, willingness to comply with all study requirements, and ability to provide informed consent.
Exclusion Criteria:
- 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.
- 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.
- Patients with acute fulminant UC and/or signs of systemic toxicity to an extent that requires immediate surgical action.
- History or presence of any colonic malignancy and/or dysplasia.
- 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.
- Treatment with antibiotics or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within two weeks before enrolment.
- An active ongoing infection.
- Positive Clostridium difficile stool assay.
- Currently receiving parenteral nutrition or blood transfusions.
- Pregnancy or breast-feeding.
- 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).
- 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.
Contacts and Locations
Show 39 Study Locations| Principal Investigator: | Christopher Hawkey, MD | Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK |
More Information
No publications provided
| Responsible Party: | InDex Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01493960 History of Changes |
| Other Study ID Numbers: | CSUC-01/10, 2011-003130-14 |
| Study First Received: | December 12, 2011 |
| Last Updated: | April 5, 2013 |
| Health Authority: | Hungary: National Institute for Quality- and Organizational Development in Healthcare and Medicines - GYEMSZI United Kingdom: Medicines and Healthcare Products Regulatory Agency UK: National Research Ethics Service Germany: Federal Institute for Drugs and Medical Devices Germany: HMS Ethics Committee Poland: Office for the Registration of Medicinal Products, Medical Devices and Biocidal Products Poland: Centralnego Szpitala Klinicznego MSWIA Czech Republic: State Institute for Drug Control Czech Republic: Ethics Committee, University Hospital Hradec Kralove Italy: Agenzia italiana del farmaco-OsSC France: Agence nationale de sécurité du médicament et des produits de santé France: Comite de protection des personnes ile de France |
Keywords provided by InDex Pharmaceuticals:
|
Colitis, Ulcerative Gastrointestinal Diseases Inflammatory Bowel Diseases Immunomodulatory Therapy |
Glucocorticoids Anti-Inflammatory Agents Therapeutic uses |
Additional relevant MeSH terms:
|
Colitis Colitis, Ulcerative Ulcer Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Colonic Diseases |
Intestinal Diseases Inflammatory Bowel Diseases Pathologic Processes Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013