A Phase III, Multicenter, Placebo-controlled, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of PROCHYMAL® (ex Vivo Cultured Adult Human Mesenchymal Stem Cells) Intravenous Infusion for the Induction of Remission in Subjects Experiencing Treatment-refractory Moderate-to-severe Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 330
- 试验地点
- 56
- 主要终点
- Disease remission (CDAI at or below 150)
研究概览
简要总结
Protocol 603 is enrolling subjects with moderate-to-severe Crohn's disease who are intolerant to, or have previously failed therapy with, at least one steroid and at least one immunosuppressant and a biologic monoclonal anti-body to tumor necrosis factor alpha. The protocol investigates the safety and efficacy of using PROCHYMAL® adult human stem cells to induce remission. PROCHYMAL is delivered through a vein in the arm four times over two weeks, for approximately an hour each time.
详细描述
A significant number of individuals with Crohn's disease do not find relief with existing steroidal, immunosuppressive, or biologic therapies, and are forced to seek surgery or other drastic measures for treatment.
PROCHYMAL® adult human stem cells are manufactured from healthy, volunteer donors, extensively tested, and are stored to be available as needed. Human and animal studies have shown that the cells do not require any donor-recipient matching. The cells may have both immunosuppressive and healing benefits in Crohn's disease. The cells naturally migrate specifically to sites of inflammation, so their effects are believed to be local and self-limiting rather than systemic.
Protocol 603 is enrolling subjects to evaluate the ability of PROCHYMAL to induce remission in subjects with moderate-to-severe disease (Crohn's disease activity index -- CDAI -- of between 250 and 450, inclusive) who have failed or been intolerant of at least one drug in each of the steroid, immunosuppressant, and biologic classes.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •failed (within last 2 yr) or intolerant of at least one steroid AND at least one immunosuppressant AND at EXACTLY one biologic
- •CDAI between 250 and 450, inclusive
- •endoscopically or radiographically confirmed Crohn's disease of ileus or colon or both
- •C-Reactive Protein Test (CRP) of at least 5 mg/l (0.5 mg/dl)*OR* CDAI of at least 300
- •weight between 40 and 150 kg, inclusive
- •adequate renal function
- •negative tuberculosis skin (PPD) test (or evaluated low risk of TB activation)
排除标准
- •HIV or hepatitis infection active
- •allergy to CT contrast agents, or to bovine or porcine products
- •symptomatic fibrostenotic Crohn's disease
- •permanent ostomy
- •biologic therapy within past 90 d
- •prednisone greater than 20 mg/d within past month
- •short-bowel syndrome
- •total parenteral nutrition
- •abnormal liver function
- •malignancy active within past 5 years (except completely resected basal or squamous cell carcinoma of skin)
- •enteric pathogens, including C. difficile
- •history of colonic mucosal dysplasia
- •current or prior evidence of tuberculosis (TB) (unless risk of activation or re-activation deemed low)
研究组 & 干预措施
Placebo
Participants will receive matching placebo administered as intravenous (IV) infusions.
干预措施: Placebo (Drug)
Prochymal® - Low dose
Participants will receive a total dose of Prochymal® 600 x 10^6 cells, IV infusion, on four days, once daily.
干预措施: Prochymal® (Drug)
Prochymal® - High dose
Participants will receive a total dose of Prochymal® 1200 x 10^6 cells, IV infusion, on four days, once daily.
干预措施: Prochymal® (Drug)
结局指标
主要结局
Disease remission (CDAI at or below 150)
时间窗: 28 days
次要结局
- Improvement in quality of life (IBDQ)(28 days)
- Reduction in number of draining fistulas(28 days)
- Disease improvement (Reduction by at least 100 points in CDAI)(28 days)