Ulcerative Colitis
Conditions
Keywords
Colitis, Ulcerative, Gastrointestinal Disease, Inflammatory Bowel Diseases, Glucocorticosteroids, Anti-Inflammatory Agents, Therapeutic uses, Cobitolimod, Toll like receptor 9 agonist, TLR9 agonist, Kappaproct, IDX0150, DIMS0150
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.
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.
Interventions
DRUGCobitolimod 250 mg
Rectal administration
DRUGCobitolimod 500 mg
Rectal administration
DRUGPlacebo
Rectal administration
Sponsors
InDex Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Canada, Croatia, Denmark, France, Georgia, Germany, Hungary, Israel, Italy, Lithuania, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, South Korea, Sweden, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed