An Open-Label, Single-Center, Investigator Initiated Phase 1B Trial of E-CEL UVEC Cell Therapy for the Treatment of Chronic Anal Fissure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of severe injection site reactions
研究概览
简要总结
This clinical trial is being conducted by investigators who are colorectal surgeons. Eligible study participants will receive the experimental treatment E-CEL UVEC cells by direct injection into the anal fissure. The study is being conducted to determine if E-CEL UVEC cell injections will be safe and would have any effects on healing of the anal fissure.
详细描述
This Phase 1b trial is conducted to evaluate the initial safety and efficacy of local (percutaneous) injections of E-CEL UVEC cells, genetically-engineered (pro-survival gene, E4ORF1+), human umbilical vein endothelial cells, as an experimental treatment of patients with chronic anal fissure (CAF) who have failed medical therapy (i.e., topical vasodilators ± botulinum injection). The study is a non-randomized, open-label, single arm study, meaning every study participant will receive some dose of the experimental study drug (no placebo). Consented, eligible participants will receive percutaneous injections of E-CEL UVEC cell product along the sides of the fissure; the treatments are spaced 3 to 4 weeks apart. Initial safety and efficacy parameters will be observed over a 6-month period, followed by a long-term follow-up consisting of annual questionnaire provided by electronic means.
This research study is being done because, in animal studies, E-CEL UVEC cells have been shown to aid in restoring or accelerating the normal healing in various tissues. This study will test if it is safe to use E-CEL UVEC cell therapy and if they it would aid in restoring or improve healing of CAF that was not responding to medical therapy. This study is being led by Dr. Kelly Garrett, Associate Professor of Surgery, and conducted by surgeons in the Colon and Rectal Surgery Division of Weill Cornell Medical College.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults 18 years and older
- •Anterior or posterior chronic anal fissure (CAF) - chronicity defined as presence of anal fissure ≥ 6 weeks
- •Inadequate response to medical treatment of anal fissure (1 month of failed vasodilator treatment plus declined or failed botulinum injection treatment)
- •Recent history of pain on defecation at a level 4 or higher on the numerical rating scale (NRS)
- •Vital signs upon screening:
- •Blood pressure: systolic ≥ 90 and < 140; and diastolic ≥ 60 and <
- •Breathing: ≥ 12 and ≤ 20 breaths per minute.
- •Pulse: ≥ 60 and ≤ 100 beats per minute.
- •Temperature: ≥ 97.8°F and ≤ 99.1°F (36.5°C to 37.3°C)
- •O2 saturation: > 92%
- •Willing to take adequate contraceptive measures
- •Willing to sign an informed consent form and follow instructions for the trial including appearing for visits and filling out questionnaires
排除标准
- •Lateral anal fissure
- •Presence of peri-anal or rectovaginal fistula, rectal or anal stenosis, or peri-anal abscess or non-healing peri-anal post-surgical wounds that are not anal fissures (subjects with history of anorectal surgery with healed surgical wound is not excluded)
- •Active, untreated or medically unresponsive infection of the anal fissure or fistula (e.g., erythema and pus)
- •Active systemic infection (e.g., bacteremia, sepsis) - stable, controlled and treated HIV+ subjects (e.g., recent plasma HIV RNA <200 copies/mL) are not excluded
- •Presence of inflammatory bowel diseases (e.g., Crohn's, ulcerative colitis)
- •Taking systemic chemotherapy or local pelvic radiation treatments
- •Renal impairment defined by serum creatinine ≥ 1.5 x upper limit of normality (ULN)
- •Hepatic impairment defined by both of the following laboratory ranges:
- •(a) total bilirubin ≥ 1.5 x ULN unless benign congenital hyperbilirubinemia; and (b) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 x ULN
- •Active alcohol or substance use that, in the opinion of the site investigator, will interfere with study follow-up.
- •Active malignant tumor (tumors must be in remission for ≥ 6 months without maintenance chemotherapy and/or radiation)
- •Ongoing or recent history (within 6 months) of abnormal, severe, progressive, or uncontrolled hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases
- •Congenital immunodeficiencies
- •History of major surgery or severe trauma within the previous 3 months
- •Subjects who are actively being considered as candidates for solid organ transplantation or who may have a high likelihood of needing a solid organ transplant (ex. Progressive heart failure)
- •Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during the study (180 days)
- •Subjects who have known hypersensitivity or documented allergy to DMSO
- •Subjects who do not wish to or cannot comply with study procedures
研究组 & 干预措施
Intervention Arm
Local percutaneous injection of E-CEL UVEC cells around the anal fissure
干预措施: E-CEL UVEC cells (AB-207) (Biological)
结局指标
主要结局
Number of severe injection site reactions
时间窗: Up to 180 days
Severe refers to Grade ≥ 3 as per CTCAE v5.0 terms and grading
Number of severe injection site reactions that are serious adverse events related to IP
时间窗: Up to 180 days
Proportion of treated responders
时间窗: Up to 180 days
Treated responders is defined as ≥ 50% reduction in pain-on-defecation (using numerical rating scale (NRS)) and ≥ 50% reduction in fissure-wound area (based on clinical examination supplemented by photo-documentation) from baseline
次要结局
- Change in proportion of treated responders(Days 0, 14, 21, 28, 42, 56, 90 and 180)
- Time-to-response in days in treated responders(Up to 180 days)
- Changes in severity of pain on defecation (NRS) from (Day 0) baseline(Days 0, 14, 21, 28, 42, 56, 90 and 180)
- Time-to complete wound closure in days in subjects who achieved complete wound closure(Up to 80)
- Percent of treatment-emergent adverse events per system organ class (SOC)(Up to 180 days)
- Proportion of treated subjects who have complete cessation of fissure-related symptoms(Up to 180 days)
- Time-to 50% wound closure in days in subjects who achieved at least 50% wound closure(Up to 180 days)
- Cumulative number of severe adverse events, defined and graded by NCI CTCAE v5.0(Up to 180 days)
- Percent of serious adverse events, including relatedness category(Up to 180 days)
- Time-to-relapse in days in subjects who experienced relapse(Up to 180 days)
- Median percent change in fissure-wound from baseline (Day 0)(Days 0, 14, 21, 28, 42, 56, 90 and 180)
- Proportion of fissure relapse in treated subjects(Up to 180 days)
- Mean percent change in fissure-wound from baseline (Day 0)(Days 0, 14, 21, 28, 42, 56, 90 and 180)
- Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)(Day 180)
- Time-to symptom improvement in days in treated subjects who achieved symptom improvement(Up to 180 days)