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

Colitis, Ulcerative Clinical Trial

— COLLECT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01493960
• Other study ID #: CSUC-01/10
• Secondary ID: 2011-003130-14
• Status: Completed
• Phase: Phase 3
• Start date: December 2011
• Est. completion date: March 2014

Study information

• Verified date: December 2022
• Source: InDex Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: March 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Cobitolimod
30 mg rectal dose at week 0 and 4
• Placebo
Rectal dose at week 0 and 4

Locations

Country	Name	City	State
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
France	Site 702	Pierre Bénite
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
Hungary	Site 205	Békéscsaba
Hungary	Site 204	Budapest
Hungary	Site 207	Budapest
Hungary	Site 203	Kaposvar
Hungary	Site 202	Szekszard
Italy	Site 302	Rome
Italy	Site 304	Rome
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
United Kingdom	Site 104	Edinburgh
United Kingdom	Site 102	London
United Kingdom	Site 103	Norwich
United Kingdom	Site 101	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
InDex Pharmaceuticals

Countries where clinical trial is conducted

Czechia,  France,  Germany,  Hungary,  Italy,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The Time to Colectomy	Median time to colectomy after 1st dose.	Within 12 months
Secondary	The Rate of Colectomy	Percentage of participants undergoing colectomy at 12 months after 1st dose.	at 12 months
Secondary	Steroid Free Remission at 12 Months	Percentage of participants with steroid free remission at 12 months after 1st dose.	at 12 months
Secondary	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
Secondary	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
Secondary	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