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

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ClinicalTrials.gov Identifier: NCT01493960
Recruitment Status : Completed
First Posted : December 16, 2011
Results First Posted : January 24, 2018
Last Update Posted : January 24, 2018
Sponsor:
Information provided by (Responsible Party):
InDex Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE December 12, 2011
First Posted Date  ICMJE December 16, 2011
Results First Submitted Date  ICMJE September 30, 2016
Results First Posted Date  ICMJE January 24, 2018
Last Update Posted Date January 24, 2018
Study Start Date  ICMJE December 2011
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
Induction of Clinical Remission [ Time Frame: Week 12 ]
The induction of clinical remission at week 12, defined as a CAI score of ≤4.(Full Analysis Set)
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2011)
Clinical remission [ Time Frame: Week 12 ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
  • The Time to Colectomy [ Time Frame: Within 12 months ]
    Median time to colectomy after 1st dose.
  • The Rate of Colectomy [ Time Frame: at 12 months ]
    Percentage of participants undergoing colectomy at 12 months after 1st dose.
  • Steroid Free Remission at 12 Months [ Time Frame: at 12 months ]
    Percentage of participants with steroid free remission at 12 months after 1st dose.
  • The Induction of Mucosal Healing [ Time Frame: Week 4 and 12 ]
    Percentage of participants with induction of mucosal healing, defined as an endoscopic score of 0 or 1, at week 4 and 12.
  • The Induction of Symptomatic Remission [ Time Frame: Week 4, 12 ]
    Percentage 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 4 and 12.
  • The Induction of Registration Remission [ Time Frame: Week 4 and 12 ]
    Percentage 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2011)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Efficacy and Safety of Cobitolimod (Kappaproct®) in Chronic Active Treatment Refractory Ulcerative Colitis Patients
Official Title  ICMJE A Placebo-controlled, Double-blind, Randomised Study to Assess the Efficacy and Safety of Cobitolimod as an add-on to Current Practice in Chronic Active Treatment Refractory Ulcerative Colitis Patients
Brief 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.
Detailed Description

The study is a placebo-controlled, double-blind, randomised study to assess the efficacy and safety of cobitolimod 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. Cobitolimod/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.

Cobitolimod (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 cobitolimod 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 cobitolimod of cobitolimod. 131 eligible patients was randomly assigned in a 2:1 allocation to receive two single rectal doses of cobitolimod 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Colitis, Ulcerative
Intervention  ICMJE
  • Drug: Cobitolimod
    30 mg rectal dose at week 0 and 4
    Other Name: DIMS0150, Kappaproct
  • Drug: Placebo
    Rectal dose at week 0 and 4
Study Arms  ICMJE
  • Experimental: Cobitolimod
    2 doses 4 weeks apart
    Intervention: Drug: Cobitolimod
  • Placebo Comparator: Placebo
    2 doses 4 weeks apart
    Intervention: Drug: Placebo
Publications * Atreya R, Reinisch W, Peyrin-Biroulet L, Scaldaferri F, Admyre C, Knittel T, Kowalski J, Neurath MF, Hawkey C. Clinical efficacy of the Toll-like receptor 9 agonist cobitolimod using patient-reported-outcomes defined clinical endpoints in patients with ulcerative colitis. Dig Liver Dis. 2018 Oct;50(10):1019-1029. doi: 10.1016/j.dld.2018.06.010. Epub 2018 Jun 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 16, 2014)
131
Original Estimated Enrollment  ICMJE
 (submitted: December 14, 2011)
120
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   France,   Germany,   Hungary,   Italy,   Poland,   United Kingdom
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01493960
Other Study ID Numbers  ICMJE CSUC-01/10
2011-003130-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party InDex Pharmaceuticals
Study Sponsor  ICMJE InDex Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christopher Hawkey, MD Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK
PRS Account InDex Pharmaceuticals
Verification Date June 2017

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