A Phase 2 Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-center Study To Investigate The Safety And Efficacy Of Multistem (Pf-05285401) In Subjects With Moderate To Severe Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 105
- 试验地点
- 58
- 主要终点
- Change From Baseline in Endoscopic Score (as Measured by Modified Baron Score) at Week 8
研究概览
简要总结
MultiStem(r) is a new biological product, manufactured from human stem cells obtained from adult bone marrow or other nonembryonic tissue sources. Factors expressed by MultiStem cells are believed to reduce inflammation and regulate immune system function, protect damaged or injured cells and tissue, promote formation of new blood vessels, and augment tissue repair and healing. MultiStem cell treatment resulted in significant efficacy in a mouse model of Graft versus Host Disease with almost complete reversal of gastrointestinal pathology (similar to pathology that would be expected in Ulcerative Colitis). These data, together with safety data generated in 2 other clinical trials, suggest that MultiStem has the potential to be a new treatment option for patients with ulcerative colitis. This is the first study of MultiStem in this patient population and will cautiously explore the safety/toleration and potential benefit of this new treatment in patients with moderate to severe disease.
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
- Triple (Participant, 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 must have a documented diagnosis of ulcerative colitis at least 6 months prior to screening.
- •Subjects must have active moderate-to-severe ulcerative colitis based on Mayo score.
- •Subjects must have Modified Baron endoscopic score of at least 2 determined within 7 days of first dosing.
- •Subjects must have failed or be intolerant (as determined by the investigator) of at least one of the following treatments for UC: Oral corticosteroids, azathioprine or 6-mercaptopurine (6-MP), or anti-tumor necrosis factor (TNF) therapy, eg, infliximab or adalimumab.
- •Subjects must be on stable steroid doses.
排除标准
- •Subjects who have abnormal organ and marrow function.
- •Subjects with a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn's disease.
- •Subjects who meet Truelove-Witts criteria for severe ulcerative colitis.
- •Subjects receiving or who are expected to receive Infliximab or other biologic treatment within 8 weeks of the Day 1 study visit.
- •Subjects receiving or who are expected to receive Cyclosporine, mycophenolate, or tacrolimus within 4 weeks of the Day 1 study visit.
研究组 & 干预措施
Cohort 3
These subjects (total n=88 evaluable patients) will receive either Placebo or MultiStem (1:1 randomization) as an intravenous infusion on Day 1. In addition all subjects in Cohort 3 will receive a single infusion of either MultiStem or Placebo at Week 8, depending on their randomization schedule. A total of ~22 patients will receive an additional infusion of MultiStem, ~44 patients will receive the alternative blinded therapy to that which they received for Day 1 infusion, and ~22 patients will receive an additional infusion of placebo.
干预措施: MultiStem high dose (Drug)
Cohort 3
These subjects (total n=88 evaluable patients) will receive either Placebo or MultiStem (1:1 randomization) as an intravenous infusion on Day 1. In addition all subjects in Cohort 3 will receive a single infusion of either MultiStem or Placebo at Week 8, depending on their randomization schedule. A total of ~22 patients will receive an additional infusion of MultiStem, ~44 patients will receive the alternative blinded therapy to that which they received for Day 1 infusion, and ~22 patients will receive an additional infusion of placebo.
干预措施: placebo (Drug)
Cohort 1
The first 9 subjects will be recruited into Cohort 1 and will receive either placebo (n=3) or MultiStem low dose (n=6) as an intravenous infusion on Day 1. The first five patients enrolled constitute a subgroup of Cohort 1 and these patients will receive multiple doses, once every day for 7 days for 3 doses (Day 1 and Weeks 1 & 2).
干预措施: placebo (Drug)
Cohort 2
This group will receive either placebo (n=3) or MultiStem high dose (n=6) as an intravenous infusion on Day 1. The subjects then receive the opposite dose of study medication at Week 8.
干预措施: placebo (Drug)
Cohort 2
This group will receive either placebo (n=3) or MultiStem high dose (n=6) as an intravenous infusion on Day 1. The subjects then receive the opposite dose of study medication at Week 8.
干预措施: MultiStem high dose (Drug)
Cohort 1
The first 9 subjects will be recruited into Cohort 1 and will receive either placebo (n=3) or MultiStem low dose (n=6) as an intravenous infusion on Day 1. The first five patients enrolled constitute a subgroup of Cohort 1 and these patients will receive multiple doses, once every day for 7 days for 3 doses (Day 1 and Weeks 1 & 2).
干预措施: MultiStem low dose (Drug)
结局指标
主要结局
Change From Baseline in Endoscopic Score (as Measured by Modified Baron Score) at Week 8
时间窗: Baseline and Week 8
Modified Baron Score is an instrument designed to measure endoscopic activity of ulcerative colitis. It classifies the mucosal inflammation in 4 grades (0=normal, 1=granular mucosa with an abnormal vascular pattern, 2=friable mucosa, 3=microulceration with spontaneous bleeding, 4=gross ulceration with spontaneous bleeding).
Change From Baseline in Rectal Bleeding Mayo Subscore at Week 4
时间窗: Baseline and Week 4
Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.
Change From Baseline in Rectal Bleeding Mayo Subscore at Week 8
时间窗: Baseline and Week 8
Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to Week 52
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Number of Participants With Treatment-Emergent AEs by System Organ Class (SOC)
时间窗: Baseline up to Week 52
Number of Treatment-Emergent AEs by Severity
时间窗: Baseline up to Week 52
The intensity grades were defined as follows: mild=does not interfere with participant's usual function; moderate=interferes to some extent with participant's usual function; severe=interferes significantly with participant's usual function.
次要结局
- Percentage of Participants With Rectal Bleeding Mayo Subscore of Zero at Weeks 4, 8, 12, and 16(Week 4, 8, 12 and 16)
- Percentage of Participants in Endoscopic Remission at Week 8(Week 8)
- Percentage of Participants in Clinical Remission at Week 8(Week 8)
- Percentage of Participants With Decrease From Baseline of at Least 1 Point in Rectal Bleeding Mayo Subscore at Weeks 4, 8, 12, and 16(Baseline, Weeks 4, 8, 12 and 16)
- Percentage of Participants With Endoscopic Response at Week 8(Week 8)
- Percentage of Participants in Clinical Response at Week 8(Week 8)
- Change From Baseline in Total Mayo Scores at Week 8(Baseline, Week 8)
- Change From Baseline in Partial Mayo Scores at Weeks 4, 8, 12, and 16(Baseline, Weeks 4, 8, 12 and 16)
- Change From Baseline in Rectal Bleeding Mayo Subscore at Week 12 and Week 16(Baseline, Week 12, Week 16)
- Number of Participants With Laboratory Test Abnormalities(Baseline up to Week 24)
- Number of Participants With Potentially Clinically Significant Vital Signs Findings(Baseline up to Week 52)
- Fold Change From Baseline in Fecal Calprotectin at Weeks 4, 8, 12, and 16(Baseline, Weeks 4, 8, 12 and 16)
- Fold Change From Baseline in C-Reactive Protein (CRP) at Weeks 4, 8, 12, and 16(Baseline, Weeks 4, 8, 12 and 16)
- Change From Baseline in Biopsy Histology Scores at Week 8(Baseline and Week 8)
- Change From Baseline in Patient-Reported Rectal Bleeding up to Week 16(Baseline and Week 16)