E-CEL UVEC as an Adjunct Cell Therapy for Treatment of Anal Fistulas

Study Overview
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Brief Summary
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The purpose of this study is to determine if endothelial cells derived from human umbilical vein are safe for use in conjunction with fistulotomy for the treatment of simple anal fistulas. Endothelial cells are a special kind of cell in the body that line the inside surface of blood vessels. The goal of the study is to evaluate the preliminary safety of human umbilical vein cells in anal fistula healing.

Detailed Description
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The purpose of this study is to test the safety of E-CEL UVEC® cells and see what effects (good and bad) it has on your anal fistula. It is hoped, that the E-CEL UVEC® cells may help to improve healing of your fistula after surgery. E-CEL UVEC® cells are genetically engineered human endothelial cells that are taken from the umbilical cords of newborn babies. The endothelial cells are cells that line the inside of blood vessels including the umbilical cord. Human umbilical endothelial cells are collected from the umbilical cord of a healthy newborn baby. The cells are obtained under strict United States (U.S.) Food and Drug Administration (FDA) regulations. The endothelial cells are engineered in the laboratory, meaning an extra gene is added. A gene is taken from a virus (just a single gene, not the entire virus) and inserted into the endothelial cells.This causes the endothelial cells to be more stable and improves their growth capabilities. In animal studies, the endothelial cells were cleared from the body within a month. No negative side effects related to the endothelial cells were seen in animal studies. A higher than normal healing response was seen in animal studies. This research study is being done because, in animal studies, E-CEL UVEC® cells have been shown to speed up healing in various tissues and organs. This study will test if it is safe to use E-CEL UVEC® cells and if they help to improve healing of your fistula after surgery.

Official Title
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An Open-Label, Single-Center, Investigator Initiated Phase 1B Trial of E-CEL UVEC as an Adjunct Cell Therapy for Treatment of Anal Fistulas

Conditions
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Anal Fistula

Intervention / Treatment
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* Drug: E-CEL UVEC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject ages 18 or older Subject willing and able to provide informed consent Subject is medically eligible and have agreed to undergo a fistulotomy Subject with simple perianal fistula with 2 or fewer fistula tracts Maximum tract length of 3 inches Subject without history of Crohn's disease/ Ulcerative Colitis For female subjects of childbearing potential: A negative serum or urine pregnancy test at screening is required prior to enrollment Subject must be willing to use a highly effective method of contraception from the start of the screening period throughout the study period For males who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception: Subject must be willing to use a recommended method of contraception and refrain from sperm donation from the start of the conditioning therapy for at least 1 year after completion and discussion with a treating physician Exclusion Criteria: Concomitant rectovaginal fistulas Subjects with an abscess Presence of active infections findings (e.g.; redness, swelling, tenderness or fever) Presence of rectal and/or anal stenosis The presence of setons unless removed prior to the treatment Subjects with ongoing steroid treatment or treated with steroids in the last 4 weeks Subjects with HbA1c ≥ 7.0 Renal impairment defined by creatinine clearance below 90 mL/min calculated using Cockcroft-Gault formula or by serum creatinine ≥ 1.5 x upper limit of normality (ULN) Hepatic impairment defined by both of the following laboratory ranges: Total bilirubin ≥ 1.5 x ULN unless benign congenital hyperbilirubinemia Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 x ULN Known history of abuse of alcohol or other addictive substances in the 6 months prior to enrollment Active malignant tumor within 5 years Current recent history of abnormal, severe, progressive, uncontrolled hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases Congenital or acquired immunodeficiencies including human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) Major surgery or severe trauma within the previous 6 months Females who are who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment Subjects who have known hypersensitivity or documented allergy to DMSO Subjects who do not wish to or cannot comply with study procedures Subjects currently receiving, or having received any investigational drug within 3 months prior to E-CEL UVEC cell therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cell Therapy Treatment<br>Patients who present with simple anal fistula and elect to undergo fistulotomy for treatment will be eligible to have E-CEL UVEC injected into the fistula at the time of fistulotomy to aid in healing. | Drug: E-CEL UVEC<br>* Injection of E-CEL UVEC<br>|
| Experimental: Cell Therapy Treatment Part B<br>Adult subjects with simple perianal fistula who meet all eligibility criteria to participate in Part B of the study will be treated in the outpatient setting with curettage and E-CEL UVEC cells without fistulotomy. E-CEL UVEC cells will be injected along the two sides (180 degrees apart from each other) of the whole length of the curetted anal fistula tract. | Drug: E-CEL UVEC<br>* Injection of E-CEL UVEC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of dose escalation, as measured by incidence rate of treatment emergent adverse events following the administration of E-CEL UVEC | The short term safety of escalating dose of E-CEL UVEC cells in subjects with anal fistulas will be assessed by monitoring and recording all adverse events for 2 weeks following the administration of E-CEL UVEC. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-Term Safety of E-CEL UVEC, as measured by the number of adverse events at 6 weeks following the administration of E-CEL UVEC | The long term safety of E-CEL UVEC cells in subjects with anal fistulas will be by assessed by monitoring and recording adverse events for 24 weeks following the administration of E-CEL UVEC. | 6 weeks | 
| Long-Term Safety of E-CEL UVEC, as measured by the number of adverse events for 24 weeks following the administration of E-CEL UVEC | The long term safety of E-CEL UVEC cells in subjects with anal fistulas will be by assessed by monitoring and recording adverse events for 24 weeks following the administration of E-CEL UVEC. | 24 weeks | 
| Efficacy of E-CEL UVEC, as measured the rate of subjects presenting with relapse in treated fistula | Efficacy of E-CEL UVEC, as measured the rate of subjects presenting with relapse in treated fistula at week 6 and 24 | 6, 24 weeks after surgery | 
| Efficacy of E-CEL UVEC, as measured by time to complete healing of each side | Efficacy of E-CEL UVEC, as measured by time to complete healing of each side of injection site | 24 weeks after surgery |