Randomized, Single-blind, Placebo Controlled Multicenter Phase III Study to Assess the Efficacy and Safety of Expanded Autologous Adipose-derived Stem Cells (ASCs) (CX-401), for Treatment of Complex Perianal Fistulas in Perianal Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 56
- 试验地点
- 12
- 主要终点
- Percentage of subjects in whom the external openings of the treated perianal fistula have closed
研究概览
简要总结
The purpose of this study is to determine safety and efficacy of eASCs (expanded adult stem cells) for treatment of complex perianal fistulas in patients with Crohn's disease.
详细描述
Complex perianal fistulas are a source of great distress for suffers. In Crohn's disease, options are limited, and surgery is often associated with incontinence and recurrence.
The biological properties of stem cells derived from adult tissues make them candidates for the treatment of pathologies requiring tissue regeneration or in diseases where the healing process is altered.
A proof-of-concept study, a phase 1 study and a phase 2 study [Clinicaltrials.gov identifier: NCT00115466] have all suggested that this approach is promising, even in patients whose fistula is associated with Crohn's disease.
The present multicenter, placebo-controlled, phase 3 study aims to confirm the efficacy and safety shown in the previous phase 1 and phase 2 studies in the treatment of complex perianal fistulas in patients with Crohn's disease after 24 weeks from initial administration. Fistula closure is defined as absence of suppuration through the external orifice with complete re-epithelization of the external orifice and absence of collections >2cm directly related to the fistula tract treated, as measured by MRI.
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
- Single (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
- •Signed informed consent
- •Patients with Crohn's disease diagnosed at least 12 months earlier in accordance with accepted clinical, endoscopic, anatomopathological and/or radiologic criteria
- •Presence of complex perianal fistula with 3 or fewer fistulous tracts assessed by MRI
- •Patients with persistent and active complex perianal fistula and non-active luminal Crohn's disease defined by a CDAI ≤
- •(Complex perianal fistula is defined as a fistula that meets one or more of the following criteria: High fistulas [high inter-sphincteric, high trans-sphincteric, extra-sphincteric or supra-sphincteric], presence of 3 or fewer external openings [tracts] associated with a complex perianal fistula, or pain/fluctuation
- •Good general state of health according to the findings of the clinical history and the physical examination
- •Women of a childbearing age with negative serum or urine pregnancy test (sensitive to 25 IU hCG). Both men and women should use appropriate birth control methods defined by the investigator
排除标准
- •Presence of severe proctitis (prominent friability, spontaneous bleeding, multiple erosions, deep ulcers) or dominant active luminal disease requiring immediate therapy, assessed by rectosigmoidoscopy
- •Patients with a CDAI ≥201
- •Patients with an abscess unless a complete toilet of the area with drainage of the collections and the absence of abscess and other collections is confirmed prior to treatment start
- •The presence of setons unless removed prior to the study procedure
- •Presence of >3 fistulous tracts and/or external openings
- •Patients with rectal and/or anal stenosis evaluated by rectoscopy or EUA
- •Patients who have received infliximab or any other anti-TNF agent in the 8 weeks before the cell treatment administration
- •Patients who have received tacrolimus or cyclosporine in the 4 weeks before the cell treatment administration
- •Patients with rectovaginal fistula, anal fistula(s), and/or non-perianal enterocutaneous fistula
- •Patients with HIV, HBV, HCV or treponema infection, whether active or latent
- •Patients with a history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion
- •Patients with malignant tumor, except for basal cell or cutaneous squamous cell carcinoma, or patients with a prior history of malignant tumors, unless the neoplastic disease has been in remission for the previous 5 years
- •Patients with cardiopulmonary disease which, in the opinion of the investigator, is unstable or sufficiently serious to exclude the patient from the study.
- •Patients with any type of medical or psychiatric disease which, in the opinion of the investigator, could be grounds for exclusion from the study
- •Patients with congenital or acquired immunodeficiencies
- •Patients with abnormal laboratory test findings that contraindicate their inclusion in the study
- •Patients allergic to local anesthetics or gadolinium (MRI contrast)
- •MRI is unfeasible, (e.g. due to the presence of pacemakers, hip replacements or severe claustrophobia)
- •Liposuction with extraction of at least 100 cm3 of fat from the abdominal wall is technically unfeasible or the patient does not consent to the procedure
- •Patients in need of surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study, or a need for such surgery is foreseen in this region in the 26 weeks after treatment administration.
- •Patients who have suffered major surgery or severe trauma in the prior 6 months
- •Pregnant or breastfeeding women
- •Patients who do not wish to or cannot comply with study procedures
- •Patients currently receiving, or having received within 1 month prior to enrolment into this clinical trial, any investigational drug
- •Patients unlikely to comply with study procedures
研究组 & 干预措施
ASCs
Intralesional dose of 20 million cells at baseline with a possible second administration of 40 million cells in case of incomplete fistula closure following week 12 assessment.
干预措施: Expanded autologous adipose-derived adult stem cells (eASCs) (Drug)
Placebo
Instillation of saline solution into the fistulous tract, following identical tract preparation process as for the investigational treatment group.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
时间窗: 24 weeks
次要结局
- Percentage of subjects in whom the external openings of the treated perianal fistula have closed(12 weeks)
- Percentage of subjects for whom surgery is avoided(24 weeks)
- Adverse events(4, 10, 12, 16, 22 and 24 weeks)
- Clinically relevant variations in vital signs(4, 10, 12, 16, 22 and 24 weeks)
- Clinically relevant variations in laboratory tests(4, 10, 12, 16, 22 and 24 weeks)
- Changes over time in the Perianal Disease Activity Index(4, 10, 12, 16, 22 and 24 weeks)
- Changes over time in the Crohn's Disease Activity Index(10 and 22 weeks)
- Changes over time in the MRI Score of Severity (MSS)(12 and 24 weeks)
- Quality of life assessment using the SF-36 questionnaire(12 and 24 weeks)