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

NCT01493960 | Completed Phase 3 Results DMC

• 2 other identifiers: CSUC-01/102011-003130-14
• Study Type: interventional
• Target: 131
• Locations: 7 countries
• Sites: 37

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.

Conditions

Colitis, Ulcerative

Keywords

Colitis, Ulcerative; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Immunomodulatory Therapy; Glucocorticoids; Anti-Inflammatory Agents; Therapeutic uses

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• The Time to Colectomy

  Within 12 months

• The Rate of Colectomy

  at 12 months

• Steroid Free Remission at 12 Months

  at 12 months

• The Induction of Mucosal Healing

  Week 4 and 12

• The Induction of Symptomatic Remission

  Week 4, 12

Study Arms (2)

Cobitolimod

EXPERIMENTAL

2 doses 4 weeks apart

Drug: Cobitolimod

Placebo

PLACEBO COMPARATOR

2 doses 4 weeks apart

Drug: Placebo

Interventions

Cobitolimod DRUG

30 mg rectal dose at week 0 and 4

Also known as: DIMS0150, Kappaproct

Cobitolimod

Placebo DRUG

Rectal dose at week 0 and 4

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• 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.
• 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.
• Ability to understand the treatment, willingness to comply with all study requirements, and ability to provide informed consent.

You may not qualify if:

• 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.
• 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.
• Patients with acute fulminant UC and/or signs of systemic toxicity to an extent that requires immediate surgical action.
• History or presence of any colonic malignancy and/or dysplasia.
• 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.
• Treatment with antibiotics or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within two weeks before enrolment.
• An active ongoing infection.
• 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.
• Known history of HIV infection based on documented history with positive serology or HIV positive serology.
• 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.
• Positive Clostridium difficile stool assay.
• Currently receiving parenteral nutrition or blood transfusions.
• Pregnancy or breast-feeding.
• 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).
• 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.

Sponsors & Collaborators

• InDex Pharmaceuticals: lead

Study Sites (37)

Site 402

Hradec Králové, Czechia

Location

Site 404

Hradec Králové, Czechia

Location

Site 406

Ostrava, Czechia

Location

Site 407

Ostrava, Czechia

Location

Site 405

Prague, Czechia

Location

Site 409

Prague, Czechia

Location

Site 403

Slaný, Czechia

Location

Site 702

Pierre-Bénite, France

Location

Site 501

Berlin, Germany

Location

Site 508

Bottrop, Germany

Location

Site 514

Erlangen, Germany

Location

Site 510

Frankfurt, Germany

Location

Site 509

Freiburg im Breisgau, Germany

Location

Site 504

Hanover, Germany

Location

Site 511

Herne, Germany

Location

Site 503

Jena, Germany

Location

Site 507

Regensburg, Germany

Location

Site 502

Stade, Germany

Location

Site 513

Stuttgart, Germany

Location

Site 205

Békéscsaba, Hungary

Location

Site 204

Budapest, Hungary

Location

Site 207

Budapest, Hungary

Location

Site 203

Kaposvár, Hungary

Location

Site 202

Szekszárd, Hungary

Location

Site 302

Rome, Italy

Location

Site 304

Rome, Italy

Location

Site 604

Krakow, Poland

Location

Site 605

Lodz, Poland

Location

Site 607

Lodz, Poland

Location

Site 606

Rzeszów, Poland

Location

Site 601

Warsaw, Poland

Location

Site 602

Warsaw, Poland

Location

Site 603

Warsaw, Poland

Location

Site 104

Edinburgh, United Kingdom

Location

Site 102

London, United Kingdom

Location

Site 103

Norwich, United Kingdom

Location

Site 101

Nottingham, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30120066 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Gastrointestinal Diseases; Inflammatory Bowel Diseases

Interventions

cobitolimod; DIMS0150

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Dr Thomas Knittel
• Organization: Index Pharmaceuticals

thomas.knittel@indexpharma.com

0046 8 508 847 31

Study Officials

• Christopher Hawkey, MD

  Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 16, 2011
• Study Start: December 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: March 1, 2014
• Last Updated: January 10, 2023
• Results First Posted: January 24, 2018

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (7); HU (5); IT (2); DE (11); GB (4); CZ (7); FR (1)