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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
InDex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01493960
First received: December 12, 2011
Last updated: June 16, 2014
Last verified: June 2014

December 12, 2011
June 16, 2014
December 2011
June 2013   (final data collection date for primary outcome measure)
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.
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, with subscores of blood in stool and number of stools weekly not exceeding 0 and 0 or 1, respectively.
Complete list of historical versions of study NCT01493960 on ClinicalTrials.gov Archive Site
  • 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.
  • The induction of symptomatic remission [ Time Frame: Week 1, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
  • 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.
Not Provided
Not Provided
 
The Efficacy and Safety of Kappaproct in Chronic Active Treatment Refractory Ulcerative Colitis Patients
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Colitis, Ulcerative
  • Drug: Kappaproct
    30 mg rectal dose at week 0 and 4
    Other Name: DIMS0150
  • Drug: Placebo
    Rectal dose at week 0 and 4
  • Experimental: Kappaproct
    2 doses 4 weeks apart
    Intervention: Drug: Kappaproct
  • Placebo Comparator: Placebo
    2 doses 4 weeks apart
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
131
March 2014
June 2013   (final data collection date for primary outcome measure)

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.
  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 study (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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Czech Republic,   France,   Germany,   Hungary,   Italy,   Poland,   United Kingdom
 
NCT01493960
CSUC-01/10, 2011-003130-14
Yes
InDex Pharmaceuticals
InDex Pharmaceuticals
Not Provided
Principal Investigator: Christopher Hawkey, MD Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK
InDex Pharmaceuticals
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP