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 Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Biocad
- 入组人数
- 204
- 试验地点
- 19
- 主要终点
- Proportion of subjects who achieved clinical remission
研究概览
简要总结
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 Crohn's Disease. The study will be conducted in a population of male and female subjects ≥18 years and ≤75 years with moderate to severe active Crohn's Disease and an inadequate response to prior treatment with glucocorticoids, immunosuppressants, or biologics/targeted immunosuppressants.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
- •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.
- •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.
- •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)
- •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, 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.
研究组 & 干预措施
BCD-261, medium dose induction/ low dose maintenance regimens
Subjects in this arm will receive a medium dose of the BCD-261 during the induction regimen (Weeks 0-12), followed by a transition to a maintenance regimen with a low dose of the BCD-261
干预措施: anti-TL1A monoclonal antibody, low dose (Biological)
BCD-261, medium dose induction/ low dose maintenance regimens
Subjects in this arm will receive a medium dose of the BCD-261 during the induction regimen (Weeks 0-12), followed by a transition to a maintenance regimen with a low dose of the BCD-261
干预措施: anti-TL1A monoclonal antibody, medium dose (Biological)
BCD-261, medium dose induction/ medium dose maintenance regimens
Subjects in this arm will receive a medium dose of the BCD261 during both the induction phase (Weeks 0-12) and the maintenance regimen
干预措施: anti-TL1A monoclonal antibody, medium dose (Biological)
BCD-261, high dose induction/ medium dose maintenance regimens
Subjects in this arm will receive a high dose of the BCD-261 during the induction regimen (Weeks 0-12), followed by a transition to a maintenance regimen with a medium dose of the BCD-261
干预措施: anti-TL1A monoclonal antibody, medium dose (Biological)
BCD-261, high dose induction/ medium dose maintenance regimens
Subjects in this arm will receive a high dose of the BCD-261 during the induction regimen (Weeks 0-12), followed by a transition to a maintenance regimen with a medium dose of the BCD-261
干预措施: anti-TL1A monoclonal antibody, high dose (Biological)
BCD-261, high dose induction/ high dose maintenance regimens
Subjects in this arm will receive a high dose of the BCD261 during both the induction phase (Weeks 0-12) and the maintenance regimen
干预措施: anti-TL1A monoclonal antibody, high dose (Biological)
Placebo
Subjects in this arm will receive placebo till the assessment of the primary endpoint and then will be switched to BCD-261medium studied dose
干预措施: Placebo (Other)
结局指标
主要结局
Proportion of subjects who achieved clinical remission
时间窗: week 14
Proportion of subjects with Crohn's Disease Activity Index (CDAI) score of \<150
Proportion of subjects who achieved an endoscopic response
时间窗: week 14
Proportion of subjects with ≥50% reduction Simple Endoscopic Score for Crohn's Disease (SES-CD) from the baseline
次要结局
- Proportion of subjects who achieved clinical remission(week 24)