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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

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.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Cobitolimod Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
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 Cobitolimod as an add-on to Current Practice in Chronic Active Treatment Refractory Ulcerative Colitis Patients
Study Start Date : December 2011
Actual Primary Completion Date : June 2013
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cobitolimod
2 doses 4 weeks apart
Drug: Cobitolimod
30 mg rectal dose at week 0 and 4
Other Name: DIMS0150, Kappaproct
Placebo Comparator: Placebo
2 doses 4 weeks apart
Drug: Placebo
Rectal dose at week 0 and 4



Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. The Time to Colectomy [ Time Frame: Within 12 months ]
    Median time to colectomy after 1st dose.

  2. The Rate of Colectomy [ Time Frame: at 12 months ]
    Percentage of participants undergoing colectomy at 12 months after 1st dose.

  3. Steroid Free Remission at 12 Months [ Time Frame: at 12 months ]
    Percentage of participants with steroid free remission at 12 months after 1st dose.

  4. 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.

  5. 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.

  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01493960


  Hide Study Locations
Locations
Czechia
Site 402
Hradec Kralove, Czechia
Site 404
Hradec Kralove, Czechia
Site 406
Ostrava, Czechia
Site 407
Ostrava, Czechia
Site 405
Prague, Czechia
Site 409
Prague, Czechia
Site 403
Slaný, Czechia
France
Site 702
Pierre Bénite, France
Germany
Site 501
Berlin, Germany
Site 508
Bottrop, Germany
Site 514
Erlangen, Germany
Site 510
Frankfurt, Germany
Site 509
Freiburg, Germany
Site 504
Hannover, Germany
Site 511
Herne, Germany
Site 503
Jena, Germany
Site 507
Regensburg, Germany
Site 502
Stade, Germany
Site 513
Stuttgart, Germany
Hungary
Site 204
Budapest, Hungary
Site 207
Budapest, Hungary
Site 205
Békéscsaba, Hungary
Site 203
Kaposvar, Hungary
Site 202
Szekszard, Hungary
Italy
Site 302
Rome, Italy
Site 304
Rome, Italy
Poland
Site 604
Krakow, Poland
Site 605
Lodz, Poland
Site 607
Lodz, Poland
Site 606
Rzeszów, Poland
Site 601
Warszawa, Poland
Site 602
Warszawa, Poland
Site 603
Warszawa, Poland
United Kingdom
Site 104
Edinburgh, United Kingdom
Site 102
London, United Kingdom
Site 103
Norwich, United Kingdom
Site 101
Nottingham, United Kingdom
Sponsors and Collaborators
InDex Pharmaceuticals
Investigators
Principal Investigator: Christopher Hawkey, MD Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK

Responsible Party: InDex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01493960     History of Changes
Other Study ID Numbers: CSUC-01/10
2011-003130-14 ( EudraCT Number )
First Posted: December 16, 2011    Key Record Dates
Results First Posted: January 24, 2018
Last Update Posted: January 24, 2018
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases