The aim of the study is to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of study drug (BCD-261) in comparison with placebo and to characterize the dose-response relationship in patients with moderate to severe active ulcerative colitis. The study will be conducted in a population of male and female subjects ≥18 years and ≤75 years with moderate to severe active ulcerative colitis and an inadequate response to prior treatment with glucocorticoids, immunosuppressants, or biologics/targeted immunosuppressants.
Persistent symptoms of disease activity despite treatment with at least one course of glucocorticoids including prednisolone at a dose of ≥40 mg/day or equivalent or budesonide ≥9 mg/day or equivalent for at least 2 weeks with oral administration (at least 1 week with intravenous administration at a dose equivalent to oral prednisolone ≥40 mg/day).
Steroid dependence manifested by an increase in disease activity after initial improvement, with a decrease in the dose of glucocorticoids below the dose equivalent to 10 mg of oral prednisolone per day, within 3 months from the beginning of treatment, or a relapse of the disease within 3 months after the end of glucocorticoid use.
Persistent symptoms of disease activity despite treatment with at least one course of immunosuppressants (azathioprine at a dose of ≥2.0 mg/kg and/or 6-mercaptopurine at a dose of ≥1.0 mg/kg) for ≥12 weeks, or in response to another treatment regimen with these drugs according to a regional standard of care.
Primary lack of response to therapy with TNFa inhibitors and/or anti-integrins, and/or IL-12/23 inhibitors, and/or Janus kinase inhibitors, and/or sphingosine-1-phosphate receptor modulators, defined as the persistence of symptoms of disease activity despite at least one course of induction of remission according to a treatment scheme approved by the regional standard.
A history of or current at the time of signing the ICF Crohn's disease, unspecified colitis, ischemic colitis, radiation colitis, microscopic colitis, complicated form of diverticular disease.
A history of primary sclerosing cholangitis.
A history of fulminant colitis, toxic dilation of the colon, intestinal obstruction, intestinal perforation (except for those caused by injury or appendicitis).
A history of dysplasia of any grade in any part of the gastrointestinal tract at the time of signing the ICF.
Parallel
anti-TL1A monoclonal antibody, low dose
Biological/Vaccineinjection
anti-TL1A monoclonal antibody, medium dose
Biological/Vaccineinjection
anti-TL1A monoclonal antibody, high dose
Biological/Vaccineinjection
Placebo
Other interventioninjection
Proportion of subjects who achieved clinical remission
Proportion of subjects with modified Mayo score ≤2 points (endoscopic mucosal score ≤1, stool blood score = 0, stool frequency score ≤1, assessment for each component should not exceed the baseline level)
Proportion of subjects who achieved clinical remission
Proportion of subjects with modified Mayo score ≤2 points (endoscopic mucosal score ≤1, stool blood score = 0, stool frequency score ≤1, assessment for each component should not exceed the baseline level)
Proportion of subjects who achieved a clinical response
Proportion of subjects modified Mayo score of ≥2 points and ≥30% from the baseline with a decrease in the estimated stool blood score of ≥1 point from the baseline or the estimated stool blood score of ≤1 point)
Proportion of subjects who achieved clinical remission
Proportion of subjects with modified Mayo score ≤2 points (endoscopic mucosal score ≤1, stool blood score = 0, stool frequency score ≤1, assessment for each component should not exceed the baseline level)
Proportion of subjects who achieved clinical remission
Proportion of subjects with modified Mayo score ≤2 points (endoscopic mucosal score ≤1, stool blood score = 0, stool frequency score ≤1, assessment for each component should not exceed the baseline level) among subjects who had a clinical response according to the modified Mayo score at Week 14
Proportion of subjects who achieved clinical remission
Proportion of subjects with modified Mayo score ≤2 points (endoscopic mucosal score ≤1, stool blood score = 0, stool frequency score ≤1, assessment for each component should not exceed the baseline level) without the use of glucocorticoids (for at least 12 weeks) among subjects who initially received glucocorticoid therapy
