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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Anal Fistula
• Intervention / Treatment: Drug: E-CEL UVEC

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Julianna Brouwer, MPH; Phone Number: 6469622394; Email: jub2024@med.cornell.edu
• Study Contact Backup: Name: Rohit Rasane; Phone Number: 646-962-2789; Email: rkr4004@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical College - NewYork-Presbyterian Hospital
      • Contact: Julianna Brouwer; Phone Number: 646-962-2394; Email: jub2024@med.cornell.edu
      • Sub-Investigator: Heather Yeo, MD
      • Sub-Investigator: Kelly Garrett, MD
      • Sub-Investigator: Lea Lowenfeld, MD
      • Sub-Investigator: Alessio Pigazzi, MD, PhD
      • Sub-Investigator: Mehraneh Jafari, MD
      • Principal Investigator: Jeffrey Milsom, MD
      • Contact: Rohit Rasane; Phone Number: 646-962-2789; Email: rkr4004@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cell Therapy Treatment; 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; Injection of E-CEL UVEC
Experimental: Cell Therapy Treatment Part B; 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; Injection of E-CEL UVEC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Angiocrine Bioscience
• Investigators: Principal Investigator: Jeffrey W Milsom, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Rectal Diseases; Intestinal Fistula; Digestive System Fistula; Fistula; Rectal Fistula
• Other Study ID Numbers: 19-04020122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No