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

Phase 3TerminatedNCT04985968

InDex Pharmaceuticals171 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

171

Conditions

Ulcerative Colitis

Interventions

Cobitolimod 250 mgDRUG

Rectal administration

Cobitolimod 500 mgDRUG

Rectal administration

PlaceboDRUG

Rectal administration

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (203)

Outcomes

Primary Outcomes

Induction - Proportion of participants with clinical remission.

Clinical remission defined by the 3-component Mayo score.

Time frame: Week 6

Maintenance - Proportion of participants with clinical remission.

Clinical remission defined by the 3-component Mayo score.

Time frame: Week 52

Secondary Outcomes

Induction - Proportion of participants with endoscopic improvement.

Endoscopic improvement defined by the Mayo Endoscopic score.

Time frame: Week 6

Induction - Proportion of participants with symptomatic remission.

Symptomatic remission defined by the 2-component Mayo score.

Time frame: Week 6

Induction - Proportion of participants with clinical response.

Clinical remission defined by the 3-component Mayo score.

Time frame: Week 6

Induction - Proportion of participants with normalisation of stool frequency.

Stool frequency defined by the Mayo score for Stool Frequency.

Time frame: Week 6

Induction - Proportion of participants with absence of rectal bleeding.

Rectal bleeding defined by the Mayo score for Rectal Bleeding.

Time frame: Week 6

Induction - Mean stool frequency.

Mean stool frequency defined by the Mayo score for Stool Frequency.

Data from ClinicalTrials.gov

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Induction - Proportion of participants with histologic improvement.

Defined by the Robarts Histologic Index.

Time frame: Week 6

Induction - Proportion of participants with histologic remission.

Histologic remission defined by the Robarts Histologic Index.

Time frame: Week 6

Induction - Proportion of participants with mucosal healing.

Mucosal healing defined by the Mayo Endoscopic score and Robarts Histologic Index.

Time frame: Week 6

Induction - Mean ln-transformed faecal calprotectin.

Mean ln-transformed faecal calprotectin defined by faecal calprotectin values.

Time frame: Week 6

Induction - Mean 3-component and 4-component Mayo scores.

Defined by 3-component and 4-component Mayo scores.

Time frame: Week 6

Induction - Mean IBDQ total score.

Defined by the Inflammatory Bowel Disease Questionnaire (IBDQ).

Time frame: Week 6

Induction - Proportion of participants with an improvement in IBDQ total score.

Defined by the IBDQ.

Time frame: Week 6

Maintenance - Proportion of participants with endoscopic improvement.

Endoscopic improvement defined by the Mayo Endoscopic score.

Time frame: Week 52

Maintenance - Proportion of participants with clinical remission and steroid-free.

Defined by the 3-component Mayo score and use of glucocorticosteroids.

Time frame: Week 52

Maintenance - Proportion of participants with clinical remission among those who achieved clinical remission

Defined by the 3-component Mayo score.

Time frame: Week 52

Maintenance - Proportion of participants with symptomatic remission.

Symptomatic remission defined by the 2-component Mayo score.

Time frame: Week 52

Maintenance - Proportion of participants with histologic improvement.

Histologic improvement defined by the Robarts Histologic Index.

Time frame: Week 52

Maintenance - Proportion of participants with histologic remission.

Histologic remission defined by the Robarts Histologic Index.

Time frame: Week 52

Maintenance - Proportion of participants with mucosal healing.

Mucosal healing defined by the Mayo Endoscopic score and Robarts Histologic Index.

Time frame: Week 52

Maintenance - Proportion of participants with clinical response.

Clinical response defined by the 3-component Mayo score.

Time frame: Week 52

Maintenance - Proportion of participants with absence of rectal bleeding.

Rectal bleeding defined by the Mayo score for Rectal Bleeding.

Time frame: Week 52

Maintenance - Proportion of participants with normalisation of stool frequency.

Stool frequency defined by the Mayo score for Stool Frequency.

Time frame: Week 52

Maintenance - Mean stool frequency.

Mean stool frequency defined by the Mayo score for Stool Frequency.

Time frame: Week 52

Maintenance - Mean ln-transformed faecal calprotectin.

Mean ln-transformed faecal calprotectin.

Time frame: Week 52

Maintenance - Mean 3-component and 4-component Mayo scores.

Defined by 3-component and 4-component Mayo scores.

Time frame: Week 52

Maintenance - Mean IBDQ total score.

Defined by the use of the Inflammatory Bowel Disease Questionnaire (IBDQ).

Time frame: Week 52

Maintenance - Proportion of participants with an improvement in IBDQ total score.

Defined by the IBDQ.

Time frame: Week 52