Clinical Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-261 in Subjects With Moderate to Severe Active Crohn's Disease

Prior treatment

• Previous resections of the small intestine with a total length of resected segments \>100 cm and/or resection of \>2 segments of the large intestine (ascending colon (including the cecum), transverse colon, descending colon (including the sigmoid colon), rectum)3.
• Failure of ≥3 classes of biologics/targeted immunosuppressors (according to INN) with different mechanisms of action (TNFa inhibitors, anti-integrins, IL-12/23 inhibitors, upadacitinib) or ≥4 biologics/targeted immunosuppressants (according to INN), regardless of the mechanism of actio
  • Use of any of the indicated therapies within the specified time frame or need for therapy with these drugs during the study period:
  • Use of TNFa inhibitors within 8 weeks prior to signing the ICF or during the screening period.
  • Use of anti-integrins or IL-12/23 inhibitors within 12 weeks before signing the ICF or during the screening period.
  • Use of Janus kinase inhibitors (upadacitinib) within 2 weeks prior to signing the ICF or during the screening period.
  • 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.
  • 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.
  • 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.
  • 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 signing the ICF or during screening.

Other illness

• A history of or current at the time of signing the ICF ulcerative colitis, unspecified colitis, ischemic colitis, radiation colitis, microscopic colitis, complicated form of diverticular disease.
• A history of primary sclerosing cholangitis.
• A history of toxic megacolon, intestinal obstruction, intestinal perforation (except for those caused by injury or appendicitis).
• A history of dysplasia in any part of the gastrointestinal tract at the time of signing the ICF.

Other

• Presence of active intra-abdominal or perianal abscess at the time of signing the ICF.
• Presence of an endoscopically obstructed stricture/stenosis of the intestine at the time of signing the ICF.
• Presence of intestinal stoma or artificial rectum or the need for them.

• The diagnosis of Crohn's disease involving the terminal ileum or colon (types L1-L3 according to the Montreal classification), established ≥3 months prior to signing the informed consent form and confirmed by endoscopic findings.
• Moderate to severe active Crohn's disease, manifested by the following signs:
  • (1) Crohn's Disease Activity Index (CDAI) ≥220 and ≤450 points.
  • (2) Simple Endoscopic Score for Crohn's Disease (SES-CD) ≥6 points or ≥4 points for the disease form with isolated involvement of the ileum (according to central independent review).
  • 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 and/or methotrexate at a dose of ≥15.0 mg/week) 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 targeted immunosuppressors (upadacitinib), 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 targeted immunosuppressors (upadacitinib), 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 glucocorticoid therapy and/or immunosuppressors (azathioprine, 6-mercaptopurine, methotrexate) and/or biologic therapies (TNFα inhibitors, anti-integrins, IL-12/23 inhibitors) and/or targeted immunosuppressors (upadacitinib), as determined 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 for ≥4 weeks prior to signing the
  • ICF and in the screening period for immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate).