CONCLUDE: The Efficacy and Safety of Cobitolimod in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis

Sponsor

InDex Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04985968

Collaborator

(none)

440

Enrollment

Locations

Arms

37.2

Anticipated Duration (Months)

17.6

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy of cobitolimod treatment compared to placebo in inducing clinical remission, in participants with moderate to severe active left-sided UC and to evaluate the efficacy of cobitolimod maintenance treatment compared to placebo in inducing or maintaining clinical remission at week 52, in participants with clinical response at week 6 after induction treatment with cobitolimod.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Cobitolimod 250 mg Drug: Cobitolimod 500 mg Drug: Placebo	Phase 3

Detailed Description

This phase III study protocol includes an induction study for 6 weeks and a maintenance study for an additional 45 weeks.

In the induction study there will be an initial phase to explore the best dose, between cobitolimod 250 mg and cobitolimod 500 mg using adaptive design.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

440 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomised Double-Blind Placebo-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Cobitolimod as an Induction and Maintenance Therapy in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis

Actual Study Start Date :

Nov 24, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cobitolimod 250 mg Dose of 250 mg cobitolimod 2 treatments during induction study and subsequently every third week	Drug: Cobitolimod 250 mg Rectal administration Other Names: Kappaproct
Experimental: Cobitolimod 500 mg Dose of 500 mg cobitolimod 2 treatments during induction study and subsequently every third week	Drug: Cobitolimod 500 mg Rectal administration Other Names: Kappaproct
Placebo Comparator: Placebo Dose of Placebo 2 treatments during induction study and subsequently every third week	Drug: Placebo Rectal administration

Arm

Intervention/Treatment

Experimental: Cobitolimod 250 mg

Dose of 250 mg cobitolimod 2 treatments during induction study and subsequently every third week

Drug: Cobitolimod 250 mg

Rectal administration

Other Names:

Kappaproct

Experimental: Cobitolimod 500 mg

Dose of 500 mg cobitolimod 2 treatments during induction study and subsequently every third week

Drug: Cobitolimod 500 mg

Rectal administration

Other Names:

Kappaproct

Placebo Comparator: Placebo

Dose of Placebo 2 treatments during induction study and subsequently every third week

Drug: Placebo

Rectal administration

Outcome Measures

Primary Outcome Measures

Induction - Proportion of participants with clinical remission. [Week 6]
Clinical remission defined by the 3-component Mayo score.
Maintenance - Proportion of participants with clinical remission. [Week 52]
Clinical remission defined by the 3-component Mayo score.

Secondary Outcome Measures

Induction - Proportion of participants with endoscopic improvement. [Week 6]
Endoscopic improvement defined by the Mayo Endoscopic score.
Induction - Proportion of participants with symptomatic remission. [Week 6]
Symptomatic remission defined by the 2-component Mayo score.
Induction - Proportion of participants with clinical response. [Week 6]
Clinical remission defined by the 3-component Mayo score.
Induction - Proportion of participants with normalisation of stool frequency. [Week 6]
Stool frequency defined by the Mayo score for Stool Frequency.
Induction - Proportion of participants with absence of rectal bleeding. [Week 6]
Rectal bleeding defined by the Mayo score for Rectal Bleeding.
Induction - Mean stool frequency. [Week 6]
Mean stool frequency defined by the Mayo score for Stool Frequency.
Induction - Proportion of participants with histologic improvement. [Week 6]
Defined by the Robarts Histologic Index.
Induction - Proportion of participants with histologic remission. [Week 6]
Histologic remission defined by the Robarts Histologic Index.
Induction - Proportion of participants with mucosal healing. [Week 6]
Mucosal healing defined by the Mayo Endoscopic score and Robarts Histologic Index.
Induction - Mean ln-transformed faecal calprotectin. [Week 6]
Mean ln-transformed faecal calprotectin defined by faecal calprotectin values.
Induction - Mean 3-component and 4-component Mayo scores. [Week 6]
Defined by 3-component and 4-component Mayo scores.
Induction - Mean IBDQ total score. [Week 6]
Defined by the Inflammatory Bowel Disease Questionnaire (IBDQ).
Induction - Proportion of participants with an improvement in IBDQ total score. [Week 6]
Defined by the IBDQ.
Maintenance - Proportion of participants with endoscopic improvement. [Week 52]
Endoscopic improvement defined by the Mayo Endoscopic score.
Maintenance - Proportion of participants with clinical remission and steroid-free. [Week 52]
Defined by the 3-component Mayo score and use of glucocorticosteroids.
Maintenance - Proportion of participants with clinical remission among those who achieved clinical remission [Week 52]
Defined by the 3-component Mayo score.
Maintenance - Proportion of participants with symptomatic remission. [Week 52]
Symptomatic remission defined by the 2-component Mayo score.
Maintenance - Proportion of participants with histologic improvement. [Week 52]
Histologic improvement defined by the Robarts Histologic Index.
Maintenance - Proportion of participants with histologic remission. [Week 52]
Histologic remission defined by the Robarts Histologic Index.
Maintenance - Proportion of participants with mucosal healing. [Week 52]
Mucosal healing defined by the Mayo Endoscopic score and Robarts Histologic Index.
Maintenance - Proportion of participants with clinical response. [Week 52]
Clinical response defined by the 3-component Mayo score.
Maintenance - Proportion of participants with absence of rectal bleeding. [Week 52]
Rectal bleeding defined by the Mayo score for Rectal Bleeding.
Maintenance - Proportion of participants with normalisation of stool frequency. [Week 52]
Stool frequency defined by the Mayo score for Stool Frequency.
Maintenance - Mean stool frequency. [Week 52]
Mean stool frequency defined by the Mayo score for Stool Frequency.
Maintenance - Mean ln-transformed faecal calprotectin. [Week 52]
Mean ln-transformed faecal calprotectin.
Maintenance - Mean 3-component and 4-component Mayo scores. [Week 52]
Defined by 3-component and 4-component Mayo scores.
Maintenance - Mean IBDQ total score. [Week 52]
Defined by the use of the Inflammatory Bowel Disease Questionnaire (IBDQ).
Maintenance - Proportion of participants with an improvement in IBDQ total score. [Week 52]
Defined by the IBDQ.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria Induction:

Male or female ≥ 18 years of age.
Established diagnosis of UC.
Moderate to severe active left-sided UC assessed by central reading.
Have inadequate response, loss of response or be intolerant of at least one of the following treatments: Oral GCS, AZA/6-MP, Biologics, JAK-inhibitors, or other approved advanced therapies for UC.
Allowed to receive a therapeutic dose of the following UC drugs during the study: Oral GCS therapy (≤20 mg prednisone or equivalent/day) , Oral 5-ASA/SP compounds, AZA/6-MP.
Ability to understand the treatment, willingness to comply with all study requirements, and ability to provide informed consent.

Exclusion Criteria Induction:

Suspicion of differential diagnosis.
Acute fulminant UC and/or signs of systemic toxicity.
UC limited to the rectum or extending beyond the splenic flexure.
Have failed treatment with more than three advanced therapies of two different therapeutic classes.
Have had surgery for treatment of UC.
History of malignancy, unless treated with no relapse of the disease and ≥ 5 years since last treatment (cured).
History or presence of any clinically significant disorder.
Concomitant treatment with cyclosporine, methotrexate, tacrolimus, or advanced therapies or similar immunosuppressants and immunomodulators.
Treatment with rectal GCS, 5-ASA/SP or tacrolimus.
Long-term treatment (>14 days) with antibiotics or NSAIDs .
Serious known active infection including history of latent or active tuberculosis.
Gastrointestinal infections including positive Clostridium difficile stool assay.
Females who are lactating or have a positive serum pregnancy test.
Women of childbearing potential not using highly effective contraceptive methods.
Concurrent participation in another clinical study.
Previous exposure to cobitolimod.

Inclusion Criteria Maintenance:

Participants are eligible to be included in the maintenance study if they have achieved clinical response at week 6 and have adhered to the protocol procedures of the induction study.

Exclusion Criteria Maintenance:

Participants will not be eligible for the maintenance study if they are not willing to comply with all further study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gastroenterology Group Of Naples	Naples	Florida	United States	34102
2	The Alfred Hospital	Melbourne		Australia
3	Universitätsklinikum Salzburg	Salzburg		Austria
4	AZ Groeninge - Campus Kennedylaan	Kortrijk		Belgium
5	Polyclinic Dr. Al-Tawil	Sarajevo		Bosnia and Herzegovina
6	University Hospital Centre Zagreb	Zagreb		Croatia
7	Hillerod Hospital	Hillerød		Denmark
8	CHU de Nancy Brabois	Nancy		France
9	JSC " Evex Hospitals"	Batumi		Georgia
10	Universitätsklinikum Erlangen	Erlangen		Germany
11	Pannónia Magánorvosi Centrum Kft	Budapest		Hungary
12	Shaare Zedek Medical Center	Jerusalem		Israel
13	Policlinico Universitario Agostino Gemelli	Roma		Italy
14	Kyung Hee University Hospital - Internal Medicine	Soeul		Korea, Democratic People's Republic of
15	Vilniaus Universiteto ligonines Santariskiu Klinikos	Vilnius		Lithuania
16	Radboud University Medical Center	Nijmegen		Netherlands
17	Vestfold Hjertesenter As	Tønsberg		Norway
18	Centrum Medyczne Plejady	Kraków		Poland
19	Hospital de Braga	Braga		Portugal
20	Cabinet Particular Policlinic Algomed	Timişoara		Romania
21	Zvezdara University Medical Center	Belgrad		Serbia
22	ENDOMED s.r.o.	Košice		Slovakia
23	Uppsala University Hospital, Akademiska	Uppsala		Sweden
24	Mersin Universtiy Medical Faculty	Mersin		Turkey
25	The Pennine Acute Hospitals NHS Trust	Manchester		United Kingdom