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
  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

Resource links provided by NLM:


Further study details as provided by InDex Pharmaceuticals:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 131
Study Start Date: December 2011
Study Completion Date: March 2014
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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01493960

  Show 39 Study Locations
Sponsors and Collaborators
InDex Pharmaceuticals
Investigators
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: June 16, 2014
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 August 28, 2014