A Phase 2a 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
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8
研究概览
简要总结
The study is designed to evaluate the clinical efficacy and safety of MEDI2070 as compared to placebo. Investigational product will be administered as intravenous infusion in double-blind period, and as a subcutaneous injection in open-label period
详细描述
This is a two-part Phase 2a study compromising a 12-week, double-blind, placebo-controlled, treatment period followed by a 100-week, open label, treatment period to evaluate short-term efficacy, and the short- and long-term safety of MEDI2070 in subjects with moderate to severe, active CD who have failed or are intolerant to anti-TNFα therapy as determined by the investigator. Approximately 120 subjects will be randomized in a 1:1 ratio to initially receive a fixed IV dose of MEDI2070 or placebo on Week 0(Day1) and Week 4 (Day 29) during the 12-week, double-blind, placebo-controlled, treatment period. At the completion of the double-blind, placebo-controlled, treatment period (Week 12), subjects will have the option to enter a 100-week, open-label, treatment period where they will receive open-label MEDI2070 (SC) Q4W (Week 12 through Week 112). Subjects will be followed for safety at 3 visits over 28 weeks after their last dose of IP. Subjects will also be contacted by phone 36 weeks after their last dose of IP for safety.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed ileal, ileo-colonic, or colonic CD at least 6 months prior to screening.
- •Men or women age 18 - 65 years at the time of screening.
- •Moderate-sever active Crohn's Disease (CD), defined by a Crohn's Disease Activity Index (CDAI) score higher or equal 220 and lower or equal 450 at Day
- •No known history of active tuberculosis (TB).
- •Received at least one anti-TNFα agent for the treatment of CD and did not initially respond.
排除标准
- •Pregnant or breastfeeding women.
- •Presence of ileostomy and/or colostomy.
- •Short bowel syndrome.
- •Bowel perforation or obstruction.
- •History of cancer.
研究组 & 干预措施
1
MEDI2070 iv infusion
干预措施: MEDI2070 (Drug)
2
placebo iv infusion
干预措施: placebo (Drug)
open-label
MEDI2070 sc injection; open-label arm is available for all subjects upon completion of first placebo-controlled treatment period
干预措施: MEDI2070 (Drug)
结局指标
主要结局
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8
时间窗: Week 8
A CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days includes subject reported symptoms, physician-assessed signs, and laboratory markers. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity. The CDAI response at Week 8 is defined as either CDAI score of less than (\<)150 or CDAI reduction from baseline of at least 100 points, where baseline was last non-missing observation prior to first administration of the study drug. Modified Intent-to-treat (mITT)population was analysed for this end point, which included all subjects who were randomized and received at least 1 dose of study drug in double-blind period.
次要结局
- Number of Participants With ADA Positive to MEDI2070 in Open-label Period(Up to 28 week post last dose (approximately 140 weeks))
- Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period(From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks))
- Percentage of Participants With CDAI-70 Point Improvement at Week 8(Week 8)
- Percentage of Participants With CDAI Response at Week 12(Week 12)
- Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period(From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks))
- Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period(Post-dose on Week 0 (Day 1); pre and post-dose on Week 4; pre-dose on Week 8)
- Percentage of Participants With CDAI Remission at Week 8(Week 8)
- Percentage of Participants With CDAI-100 Point Improvement at Week 8(Week 8)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period(From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks))
- Change From Baseline in CDAI Total Score at Week 8(Week 8)
- Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period(From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks))
- Number of Participants With TEAEs in Open-label Period(From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks))
- Number of Participants With TESAEs in Open-label Period(From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks))
- Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period(From study drug administration (Day 1) to 36 weeks post last blinded dose (up to 48 weeks))
- Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period(From first open-label dose administration (Week 12) to 36 weeks post last dose (up to 148 weeks))
- Number of Participants With Positive Anti-drug Antibody (ADA) to MEDI2070 in Double-blind Period(Baseline (Week0/Day 1) up to 28 week post last dose (approximately 40 weeks))
- Maximum Mean Serum Concentration of MEDI2070 in Open-label Period(Pre-dose on Weeks 12, 24, and 112)