A Phase 2b Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MEDI2070 in Subjects With Moderate to Severe Crohn's Disease Who Have Failed or Are Intolerant to Anti-tumor Necrosis Factor-alpha Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 29
- 试验地点
- 51
- 主要终点
- Percentage of Participants With Crohn's Disease Activity Index (CDAI) Remission at Week 8
研究概览
简要总结
A Phase 2b study to evaluate the efficacy and safety of brazikumab (MEDI2070) in participants with moderate to severe Crohn's disease who have failed or are intolerant to anti-tumor necrosis factor-alpha (anti-TNFα) therapy.
详细描述
This is a four-part Phase 2b study comprised of a 16-week, double-blind, placebo-controlled, Induction Period, a 12-week double-blind, placebo-controlled, Maintenance Period, a 24-week, Open-label Period and a post-treatment 28 week observational safety follow-up period designed to evaluate the short-term efficacy and the short- and long term safety of brazikumab in participants with moderate to severe, active Crohn's disease (CD) who have failed or are intolerant to anti-TNFα therapy as determined by the Investigator.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of ileal, ileo-colonic, or colonic Crohn's Disease (CD) for > 3 months prior to screening
- •Men or women age 18 - 80 years at the time of screening
- •Moderate to severely active CD, as defined by Crohn's Disease Activity Index (CDAI) and endoscopic demonstration of inflammation
- •Stable dose of medications for Crohn's disease therapy
- •Prior treatment failure or intolerance with at least one Anti-Tumor Necrosis Factor-Alpha Therapy (anti-TNF α) agent
- •Effective contraception from screening, and for 36 weeks after the last dose of investigational product
- •No known history of active tuberculosis (TB) & negative assessment for TB/latent TB
排除标准
- •Severe underlying immunosuppression
- •Severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation
- •Significant infections at screening; Infected abscess, positive for Clostridium difficile, recent infectious hospitalization
- •Recent treatment with approved or investigational biologic therapy for Crohn's disease
- •Recent or planned live attenuated vaccine
- •History of cancer, except for basal cell carcinoma or carcinoma in situ (CIS) of the cervix with apparent cure ≥ 12 months before screening
- •Pregnancy/breast feeding
- •Drug abuse
研究组 & 干预措施
Placebo
Placebo-matching brazikumab intravenous (IV) infusion and subcutaneous (SC) injection at Weeks 0 and 4 followed by placebo-matching brazikumab SC injection at Weeks 8 and 12 in the induction phase and at Weeks 16, 20 and 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection every 4 weeks up to Week 48 in the open-label period.
干预措施: Brazikumab IV Infusion (Drug)
Placebo
Placebo-matching brazikumab intravenous (IV) infusion and subcutaneous (SC) injection at Weeks 0 and 4 followed by placebo-matching brazikumab SC injection at Weeks 8 and 12 in the induction phase and at Weeks 16, 20 and 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection every 4 weeks up to Week 48 in the open-label period.
干预措施: Brazikumab SC Injection (Drug)
Placebo
Placebo-matching brazikumab intravenous (IV) infusion and subcutaneous (SC) injection at Weeks 0 and 4 followed by placebo-matching brazikumab SC injection at Weeks 8 and 12 in the induction phase and at Weeks 16, 20 and 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection every 4 weeks up to Week 48 in the open-label period.
干预措施: Placebo (Drug)
Brazikumab High Dose
Brazikumab 700 mg, IV infusion and placebo-matching brazikumab, SC injection at Weeks 0 and 4 followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.
干预措施: Brazikumab IV Infusion (Drug)
Brazikumab High Dose
Brazikumab 700 mg, IV infusion and placebo-matching brazikumab, SC injection at Weeks 0 and 4 followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.
干预措施: Brazikumab SC Injection (Drug)
Brazikumab High Dose
Brazikumab 700 mg, IV infusion and placebo-matching brazikumab, SC injection at Weeks 0 and 4 followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.
干预措施: Placebo (Drug)
Brazikumab High-Medium Dose
Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.
干预措施: Brazikumab IV Infusion (Drug)
Brazikumab High-Medium Dose
Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.
干预措施: Brazikumab SC Injection (Drug)
Brazikumab High-Medium Dose
Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.
干预措施: Placebo (Drug)
Brazikumab Low-Medium Dose
Brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 105 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 105 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 105 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
干预措施: Brazikumab IV Infusion (Drug)
Brazikumab Low-Medium Dose
Brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 105 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 105 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 105 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
干预措施: Brazikumab SC Injection (Drug)
Brazikumab Low-Medium Dose
Brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 105 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 105 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 105 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
干预措施: Placebo (Drug)
Brazikumab Low Dose
Brazikumab 70 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 35 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 35 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 35 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
干预措施: Brazikumab IV Infusion (Drug)
Brazikumab Low Dose
Brazikumab 70 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 35 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 35 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 35 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
干预措施: Brazikumab SC Injection (Drug)
Brazikumab Low Dose
Brazikumab 70 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 35 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 35 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 35 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Remission at Week 8
时间窗: Week 8
CDAI remission was defined as a CDAI score of \<150 at Week 8. CDAI score was calculated by summing weighted scores for subjective items \[number of liquid or very soft stools, abdominal pain (on a scale of 0=none to 3=severe) and general well-being (on a scale of 1=generally well to 4=terrible)\] recorded by a diary during a 1-week period, and objective items \[associated symptoms, taking antidiarrheal agents such as loperamide/opiates, abdominal mass, hematocrit, daily morning temperature, and body weight\]. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
次要结局
- Percentage of Participants With Loose/Liquid Stool Frequency Response(Baseline, Weeks 8, 16 and 28)
- Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Response(Baseline, Weeks 16 and 28)
- Percentage of Participants With Loose/Liquid Stool Frequency Remission(Baseline, Weeks 8, 16 and 28)
- Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Remission(Weeks 16 and 28)
- Percentage of Participants With PRO2 Response(Baseline, Weeks 8, 16 and 28)
- Number of Participants With Clinically Significant Laboratory Values(From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80))
- Percentage of Participants With CDAI Clinical Remission(Weeks 16 and 28)
- Number of Participants With Serum Anti-drug Antibodies for Brazikumab(Predose at Weeks 0, 4, 12, 16, 28, 40 and 52)
- Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response(Baseline, Weeks 8, 16 and 28)
- Serum Interleukin (IL)-22 and Serum Lipocalin 2 (LCN2) Concentration as a Biomarker of Brazikumab's Efficacy(Weeks 16 and 28)
- Percentage of Participants With Abdominal Pain Response(Baseline; Weeks 8, 16 and 28)
- Percentage of Participants With Patient Response Outcome-2 (PRO2) Remission(Weeks 8, 16 and 28)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), TEAEs of Special Interest and TEAEs Leading to Discontinuation(From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80))
- Percentage of Participants With CDAI Modified Sustained Clinical Remission at Both Weeks 8 and 28(Weeks 8 and 28)
- Serum Brazikumab Concentration(Predose at Weeks 0, 1, 4, 8, 12, 16, 28; Postdose at Weeks 0 and 4)
- Percentage of Participants With Abdominal Pain Remission(Weeks 8, 16 and 28)