A 52 Week Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Maintenance of Remission in Subjects With Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 229
- 试验地点
- 1
- 主要终点
- Percentage of Participants in Clinical Remission (Crohn's Disease Activity Index , CDAI Score <150 Points) at Both Weeks 28 and 52 of the 52-week Treatment Period
研究概览
简要总结
A randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two doses (500 mg once daily and 500 mg twice daily) of GSK1605786A in maintaining remission over 52 weeks in adult subjects with Crohn's disease. Efficacy will be assessed by the Crohn's Disease Activity Index (CDAI) score. Eligible subjects will have achieved response (CDAI decrease of at least 100 points) and/or remission (CDAI less than 150) in a prior GSK sponsored induction study. The primary endpoint will be proportion of subjects in remission at both Weeks 28 and 52. Safety will be assessed by recording of adverse events, clinical laboratory parameters including liver function tests, vital signs and electrocardiogram. Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work Productivity and Activity Impairment - Crohn's Disease (WPAI-CD) and disability.
详细描述
This is a multi-centre, randomised, placebo-controlled, double-blind parallel group study in adult subjects with Crohn's disease who previously achieved clinical response (CDAI decrease of at least 100 points) and/or remission (CDAI less than 150) in a prior Phase III induction study (Study CCX114151 or another GSK sponsored induction study). Subjects will be randomised to 52 weeks of oral treatment with GSK1605786A 500 mg once daily or 500 mg twice daily or placebo. Subjects who are receiving concomitant corticosteroids at entry will undergo dose tapering following a defined schedule. Subjects who complete the treatment period may be eligible to enter an open-label extension study. Subjects who experience disease worsening and require additional (rescue) treatment will be withdrawn and may be eligible to enter the open-label study. Subjects who do not enter the open-label study must complete a follow-up assessment 4 weeks after completion of treatment. Approximately 756 subjects will be enrolled.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects achieving clinical response (CDAI decrease of at least 100 points) and/or remission (CDAI less than 150) upon completion of treatment in Study CCX114151 or another GSK sponsored induction study
- •Written informed consent prior to any CCX114157 specific study procedures
- •Females of child-bearing potential must be sexually inactive or commit to use of consistent and correct use of contraceptive methods with a failure rate of less than 1 percent
- •Stable doses of Crohn's disease medications
- •Subjects on corticosteroids at entry must be willing to undergo corticosteroid dose taper during the study
排除标准
- •If female, is pregnant, has a positive pregnancy test or is breast-feeding
- •Subjects with known or suspected coeliac disease or a positive screening test (anti-tissue transglutaminase antibodies) should have been excluded from enrolment into the induction studies. Subjects in whom a diagnosis of coeliac disease is subsequently suspected should have this excluded with testing for anti-tissue transglutaminase antibodies prior to enrolment into the maintenance study.
- •Known or suspected fixed symptomatic small bowel stricture
- •Enterocutaneous, abdominal or pelvic fistulae likely to require surgery during the study period
- •Current sepsis or infections requiring intravenous antibiotic therapy for greater than 2 weeks
- •Evidence of hepatic dysfunction, viral hepatitis, or liver function abnormalities
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
GSK1605786A once daily
500 milligrams once daily
干预措施: GSK1605786A (Drug)
GSK1605786A twice daily
500 milligrams twice daily
干预措施: GSK1605786A (Drug)
结局指标
主要结局
Percentage of Participants in Clinical Remission (Crohn's Disease Activity Index , CDAI Score <150 Points) at Both Weeks 28 and 52 of the 52-week Treatment Period
时间窗: Week 28 and 52
Clinical remission is defined as a CDAI score \<150 points. In the missing=no effect imputation, participants with missing CDAI scores was considered not to be in clinical remission. Data for percentage of participants in at both Weeks 28 and 52 of the 52-week treatment period have been presented.
次要结局
- Percentage of Participants in Clinical Remission (CDAI Score <150 Points) and Not Taking Corticosteroids at Both Weeks 28 and 52 of the 52-week Treatment Period(Week 28 and 52)
- Percentage of Participants in Clinical Remission at Both Weeks 28 and 52 of the 52-week Treatment Period Among Those Participants Who Were in Clinical Remission at Baseline(Week 28 and 52)
- Percentage of Participants in Clinical Remission at All Visits (Continuous Clinical Remission) During the 52-week Treatment Period Among Participants in Clinical Remission at Baseline(Upto Week 52)
- Percentage of Participants in Clinical Remission at Week 52(Week 52)
- Percentage of Participants With a Clinical Response (CDAI Decrease >=100 Points) at Both Weeks 28 and 52 of the 52-week Treatment Period(Week 28 and 52)
- Time to Induction of Clinical Remission in Participants Who Had Achieved Clinical Response During Induction Therapy But Were Not in Clinical Remission at Baseline(Upto Week 52)
- Change From Baseline in CDAI Score at Weeks 4, 8, 12, 20, 28, 36, 44, and 52(Baseline (Week 0) and Weeks 4, 8, 12, 20, 28, 36, 44, and 52)
- Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 52(Baseline (Week 0) and Week 52)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Upto 56 weeks)
- Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56(Baseline (Week 0) and Weeks 4, 8, 12, 20, 28, 36, 44, 52, 56)
- Change From Baseline in Vital Sign Heart Rate Upto Week 56(Baseline (Week 0) and Weeks 4, 8, 12, 20, 28, 36, 44, 52 and 56)
- Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56(Baseline (Week 0) and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56)
- Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56(Baseline (Week 0) and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56)
- Number of Participants With 12 Lead Electocardiogram (ECG) Abnormalities at Week 28 and 52(Week 28 and 52)
- Change From Baseline in Short Form - 36 Version 2 (SF-36 v2) at Weeks 28 and 52(Baseline (Week 0) and Weeks 28 and 52)
- Number of Participants With Shift From Baseline in Hematology Parameters(Upto Week 56)
- Number of Participants With Shift From Baseline in Clinical Chemistry Parameters(Upto Week 56)
- Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56.(Baseline (Week 0) and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56.)
- Change From Baseline in European Quality of Life (EuroQol ) Five Dimensions Questionnaire (EQ-5D) at Weeks 28 and 52(Baseline (Week 0) and Weeks 28 and 52)
- Change From Baseline in Work Productivity & Activity Impairment - Crohn's Disease (WPAI-CD) at Weeks 28 and 52(Baseline (Week 0) and Weeks 28 and 52)
- Receipt of Disability Benefits at Weeks 28 and 52(Weeks 28 and 52)
- Change From Baseline in Health-related Resource Utilization at Weeks 28 and 52(Baseline (Week 0) and Weeks 28 and 52)
- Change From Baseline in C Reactive Protein (CRP) at Weeks 28 and 52(Baseline (Week 0 and Weeks 28 and 52)
- Change From Baseline in Faecal Calprotectin at Weeks 28 and 52(Baseline (Week 0) and Weeks 28 and 52)