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

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

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.

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Cobitolimod; Drug: Placebo

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
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Hradec Kralove, Czechia
    • Site 402
  • Hradec Kralove, Czechia
    • Site 404
  • Ostrava, Czechia
    • Site 406
  • Ostrava, Czechia
    • Site 407
  • Prague, Czechia
    • Site 405
  • Prague, Czechia
    • Site 409
  • Slaný, Czechia
    • Site 403
• France
  • Pierre Bénite, France
    • Site 702
• Germany
  • Berlin, Germany
    • Site 501
  • Bottrop, Germany
    • Site 508
  • Erlangen, Germany
    • Site 514
  • Frankfurt, Germany
    • Site 510
  • Freiburg, Germany
    • Site 509
  • Hannover, Germany
    • Site 504
  • Herne, Germany
    • Site 511
  • Jena, Germany
    • Site 503
  • Regensburg, Germany
    • Site 507
  • Stade, Germany
    • Site 502
  • Stuttgart, Germany
    • Site 513
• Hungary
  • Budapest, Hungary
    • Site 204
  • Budapest, Hungary
    • Site 207
  • Békéscsaba, Hungary
    • Site 205
  • Kaposvar, Hungary
    • Site 203
  • Szekszard, Hungary
    • Site 202
• Italy
  • Rome, Italy
    • Site 302
  • Rome, Italy
    • Site 304
• Poland
  • Krakow, Poland
    • Site 604
  • Lodz, Poland
    • Site 605
  • Lodz, Poland
    • Site 607
  • Rzeszów, Poland
    • Site 606
  • Warszawa, Poland
    • Site 601
  • Warszawa, Poland
    • Site 602
  • Warszawa, Poland
    • Site 603
• United Kingdom
  • Edinburgh, United Kingdom
    • Site 104
  • London, United Kingdom
    • Site 102
  • Norwich, United Kingdom
    • Site 103
  • Nottingham, United Kingdom
    • Site 101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cobitolimod; 2 doses 4 weeks apart	Drug: Cobitolimod; 30 mg rectal dose at week 0 and 4; Other Names: DIMS0150, Kappaproct
Placebo Comparator: Placebo; 2 doses 4 weeks apart	Drug: Placebo; Rectal dose at week 0 and 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction of Clinical Remission	The induction of clinical remission at week 12, defined as a CAI score of ≤4.(Full Analysis Set)	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Time to Colectomy	Median time to colectomy after 1st dose.	Within 12 months
The Rate of Colectomy	Percentage of participants undergoing colectomy at 12 months after 1st dose.	at 12 months
Steroid Free Remission at 12 Months	Percentage of participants with steroid free remission at 12 months after 1st dose.	at 12 months
The Induction of Mucosal Healing	Percentage of participants with induction of mucosal healing, defined as an endoscopic score of 0 or 1, at week 4 and 12.	Week 4 and 12
The Induction of Symptomatic Remission	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.	Week 4, 12
The Induction of Registration Remission	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.	Week 4 and 12

Collaborators and Investigators

• Sponsor: InDex Pharmaceuticals
• Investigators: Principal Investigator: Christopher Hawkey, MD, Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: December 12, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 16, 2011

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Gastrointestinal Diseases; Glucocorticoids; Inflammatory Bowel Diseases; Colitis, Ulcerative; Anti-Inflammatory Agents; Therapeutic uses; Immunomodulatory Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: CSUC-01/10; 2011-003130-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No