Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-261 in Subjects With Moderate to Severe Active Ulcerative Colitis

Official title

A Randomized Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-261 in Subjects With Moderate to Severe Active Ulcerative Colitis

Overview

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.

Detailed description

Subjects meeting the eligibility criteria will be randomized in 5 groups to receive one of four studied dosage regimens of BCD-261 or placebo. The study groups will differ in drug dosages of BCD-261 (low, medium, high) during the induction and maintenance periods of therapy. After the primary endpoint assessment subjects in placebo group will be switched to BCD-261 medium studied dose.

Interventions

• Biological anti-TL1A monoclonal antibody, low dose
  injection
• Biological anti-TL1A monoclonal antibody, medium dose
  injection
• Biological anti-TL1A monoclonal antibody, high dose
  injection
• Other Placebo
  injection

Primary outcome measures

• Proportion of subjects who achieved clinical remission [Time frame: week 14]

Secondary outcome measures (1)

• Proportion of subjects who achieved clinical remission [Time frame: week 24]

Eligibility criteria

Inclusion criteria

1\. Diagnosis of ulcerative colitis with involvement of the colon proximal to the rectum (≥15 cm from the distal edge of the anal canal), established ≥3 months before signing the ICF and confirmed by endoscopic examination data.

2\. Moderate to severe active ulcerative colitis with a modified Mayo score (mMS) of ≥4 and ≤9 points, which includes an endoscopic component of ≥2 points (according to a central independent review) and a stool blood score of ≥1 point.

3\. Inadequate response to therapy according to the investigator's assessment, manifested by at least one of the following signs:

• 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.
• Loss 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 appearance of symptoms of disease activity after initial improvement as a result of treatment with at least one course of induction of remission and at least one course of maintenance of remission according to a treatment scheme approved by the regional standard.
• A history of intolerance to glucocorticoids and/or immunosuppressants (azathioprine, 6-mercaptopurine) and/or biological therapy/targeted immunosuppressants (TNFa inhibitors, anti-integrins, anti-IL-12/23 monoclonal antibodies, Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators) established by the treating physician.

4\. Maintaining a stable dose of concomitant medications for ≥2 weeks prior to signing the ICF and in the screening period for glucocorticoids and 5-ASCs and for ≥4 weeks prior to signing the ICF and in the screening period for immunosuppressants (azathioprine, 6-mercaptopurine).

Exclusion criteria

• 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.
• Presence of intestinal stoma or artificial rectum or the need for them.
• Failure of ≥3 classes of biologics/targeted immunosuppressors (according to INN) with different mechanisms of action (TNFa inhibitors, anti-integrins, IL-12/23 inhibitors, Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators) or ≥4 biologics/targeted immunosuppressants, regardless of the mechanism of action.
• Use of any of the indicated therapies within the specified time frame or need for therapy with these drugs during the study period:

(1) Use of Janus kinase inhibitors within 2 weeks prior to signing the ICF or during the screening period.

(2) Use of TNFa inhibitors within 8 weeks prior to signing the ICF or during the screening period.

(3) Using modulators of sphingosine-1-phosphate receptors within 10 weeks prior to signing the ICF or during the screening period.

(4) Use of anti-integrins, IL-12/23 inhibitors within 12 weeks before signing the ICF or during the screening period.

(5) Use of oral glucocorticoids at a dose equivalent to prednisone >20 mg/day or budesonide >9 mg/day or rectal administration of glucocorticoids at any dose within

2 weeks prior to signing the ICF or during the screening period or parenteral administration of glucocorticoids at any dose within 4 weeks prior to signing the ICF or during the screening period.

(6) Rectal administration of 5-ASCs within 2 weeks prior to signing the ICF or during the screening period.

(7) Use of immunosuppressants not included in the approved therapy (tacrolimus, cyclosporine, mycophenolate mofetil, rapamycin, leflunomide, penicillamine, etc.) within 4 weeks before signing the ICF or during the screening period.

(8) Long-term regular use of non-steroidal anti-inflammatory drugs (≥3 times a week for ≥6 weeks) for 2 weeks prior to signing the ICF.

(9) Use of any other investigational drugs in other clinical trials at the time of signing the ICF or less than 8 weeks or 5 half-lives (whichever is longer) before the date of randomization.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Russia · 20 centers

• LLC Medical Center "ASTRA" — Barnaul
• Republican Clinical Hospital named after G.G. Kuvatov — Ufa
• Federal State Educational Institution of Higher Education "Rostov State Medical University — Rostov-on-Don
• Federal State Educational Institution of Higher Education "Rostov State Medical University — Rostov-on-Don
• State Autonomous Institution of Healthcare "Republican Clinical Hospital of the Ministry o — Kazan'
• "South Ural State Medical University" of the Ministry of Health of the Russian Federation — Chelyabinsk
• Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agen — Krasnoyarsk
• Regional State Healthcare Institution "Regional Clinical Hospital" — Krasnoyarsk
• … and 12 more centers

Identifiers

NCT: NCT07080034 · BCD-261-4

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗