Colitis, UlcerativePhase 3COLLECTNCT01493960
The Efficacy and Safety of Cobitolimod (Kappaproct®) in Chronic Active Treatment Refractory Ulcerative Colitis Patients
A Phase 3 study testing Cobitolimod in people with Colitis, Ulcerative, run by InDex Pharmaceuticals at 37 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Cobitolimod
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 37 sitesin 7 countries
- Study dates
- Dec 2011to Mar 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
37 sites in 7 countries.
37 sites in 7 countries
Germany11 sites
Site 501
Berlin
Site 508
Bottrop
Site 514
Erlangen
Site 510
Frankfurt
Site 509
Freiburg im Breisgau
Site 504
Hanover
Site 511
Herne
Site 503
Jena
Site 507
Regensburg
Site 502
Stade
Site 513
Stuttgart
Czechia7 sites
Site 402
Hradec Králové
Site 404
Hradec Králové
Site 406
Ostrava
Site 407
Ostrava
Site 405
Prague
Site 409
Prague
Site 403
Slaný
Poland7 sites
Site 604
Krakow
Site 605
Lodz
Site 607
Lodz
Site 606
Rzeszów
Site 601
Warsaw
Site 602
Warsaw
Site 603
Warsaw
Hungary5 sites
Site 205
Békéscsaba
Site 204
Budapest
Site 207
Budapest
Site 203
Kaposvár
Site 202
Szekszárd
United Kingdom4 sites
Site 104
Edinburgh
Site 102
London
Site 103
Norwich
Site 101
Nottingham
About this study
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
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.
Read the 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.
- Conditions
- Colitis, Ulcerative
- Being tested
- Cobitolimod, Placebo
- Keywords
- Colitis, Ulcerative, Gastrointestinal Diseases, Inflammatory Bowel Diseases, Immunomodulatory Therapy, Glucocorticoids, Anti-Inflammatory Agents, Therapeutic uses
- Medical subject headings
- Colitis, Ulcerative, Gastrointestinal Diseases, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobitolimodDrug
Also called DIMS0150, Kappaproct
30 mg rectal dose at week 0 and 4
PlaceboDrug
Rectal dose at week 0 and 4
| Study group | Role | What they receive |
|---|---|---|
| Cobitolimod | Experimental | 2 doses 4 weeks apart Receives: Drug: Cobitolimod |
| Placebo | Placebo comparator | 2 doses 4 weeks apart Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Induction of Clinical Remission
The induction of clinical remission at week 12, defined as a CAI score of ≤4.(Full Analysis Set)
Measured: Week 12
Secondary outcomes (6)
The Time to Colectomy
Median time to colectomy after 1st dose.
Measured: Within 12 months
The Rate of Colectomy
Percentage of participants undergoing colectomy at 12 months after 1st dose.
Measured: at 12 months
Steroid Free Remission at 12 Months
Percentage of participants with steroid free remission at 12 months after 1st dose.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 4 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionJun 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- InDex Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christopher Hawkey, MD, Principal investigator, Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01493960
- Sponsor's protocol ID
- CSUC-01/10
- Other IDs
- 2011-003130-14
- Acronym
- COLLECT
- Status last verified
- Dec 2022
- First submitted
- 12 Dec 2011
- Last updated
- 10 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 30120066
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01493960
- Acronym / sponsor ID
- COLLECT / CSUC-01/10
- Conditions
- Colitis, Ulcerative
- Keywords
- Colitis, Ulcerative, Gastrointestinal Diseases, Inflammatory Bowel Diseases, Immunomodulatory Therapy, Glucocorticoids, Anti-Inflammatory Agents, Therapeutic uses
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- InDex PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 16 Dec 2011 (estimated)
- Results
- Posted 24 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cobitolimod | Experimental | Drug: Cobitolimod2 doses 4 weeks apart |
| Placebo | Placebo comparator | Drug: Placebo2 doses 4 weeks apart |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobitolimodAlso: DIMS0150, Kappaproct30 mg rectal dose at week 0 and 4 | Drug | Cobitolimod |
| PlaceboRectal dose at week 0 and 4 | Drug | Placebo |
Primary outcome
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)
6 secondary outcomes
The Time to Colectomy
Time frame: Within 12 months
The Rate of Colectomy
Time frame: at 12 months
Steroid Free Remission at 12 Months
Time frame: at 12 months
The Induction of Mucosal Healing
Time frame: Week 4 and 12
The Induction of Symptomatic Remission
Time frame: Week 4, 12
The Induction of Registration Remission
Time frame: Week 4 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30120066Atreya 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.
- Individual participant dataSharing planned: No
Related trials for Colitis, Ulcerative
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Hawkey, MD principal investigator
Nottingham Digestive Diseases Centre, Queens Campus University Hospitals, Nottingham, UK
37 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cobitolimod in people with Colitis, Ulcerative, run by InDex Pharmaceuticals at 37 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in Germany, Czechia, Poland, Hungary, United Kingdom and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Induction of Clinical Remission (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01493960, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2023.