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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Biocad
- 入组人数
- 198
- 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 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.
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
- •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).
排除标准
- •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.
研究组 & 干预措施
BCD-261, medium dose induction/ low dose maintenance regimens
Group 1: Subjects in this arm will receive a medium dose of the BCD-261 subcutaneously once every 4 weeks until Week 12 during the induction regimen (Weeks 0-12), followed by a transition to a maintenance regimen with a low dose of the BCD-261 once every 8 weeks from Week 20 to Week 100.
干预措施: anti-TL1A monoclonal antibody, low dose (Biological)
BCD-261, medium dose induction/ low dose maintenance regimens
Group 1: Subjects in this arm will receive a medium dose of the BCD-261 subcutaneously once every 4 weeks until Week 12 during the induction regimen (Weeks 0-12), followed by a transition to a maintenance regimen with a low dose of the BCD-261 once every 8 weeks from Week 20 to Week 100.
干预措施: anti-TL1A monoclonal antibody, medium dose (Biological)
BCD-261, medium dose induction/ medium dose maintenance regimens
Group 2: Subjects in this arm will receive a medium dose of the BCD261 subcutaneously once every 4 weeks until Week 12 during the induction regimen (Weeks 0-12), followed by the maintenance regimen with the same dose of the BCD-261 once every 8 weeks from Week 20 to Week 100.
干预措施: anti-TL1A monoclonal antibody, medium dose (Biological)
BCD-261, high dose induction/ medium dose maintenance regimens
Group 3: Subjects in this arm will receive a high dose of the BCD-261 subcutaneously once every 4 weeks until Week 12 during the induction regimen (Weeks 0-12) , followed by a transition to a maintenance regimen with a medium dose of the BCD-261 once every 8 weeks from Week 20 to Week 100.
干预措施: anti-TL1A monoclonal antibody, medium dose (Biological)
BCD-261, high dose induction/ medium dose maintenance regimens
Group 3: Subjects in this arm will receive a high dose of the BCD-261 subcutaneously once every 4 weeks until Week 12 during the induction regimen (Weeks 0-12) , followed by a transition to a maintenance regimen with a medium dose of the BCD-261 once every 8 weeks from Week 20 to Week 100.
干预措施: anti-TL1A monoclonal antibody, high dose (Biological)
BCD-261, high dose induction/ high dose maintenance regimens
Group 4: Subjects in this arm will receive a high dose of the BCD261 subcutaneously once every 4 weeks until Week 12 during the induction regimen (Weeks 0-12), followed by maintenance regimen with with the same dose of the BCD-261 once every 8 weeks from Week 20 to Week 100.
干预措施: anti-TL1A monoclonal antibody, high dose (Biological)
Placebo
Group 5: Subjects in this arm will receive placebo subcutaneously at Weeks 0, 4, 8, and 12, followed by a medium dose of the BCD-261 subcutaneously once every 4 weeks until Week 28 , followed by a transition to a low dose of the BCD-261 once every 8 weeks from Week 36 to Week 100.
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 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)
次要结局
- Proportion of subjects who achieved clinical remission(week 24)