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

• ClinicalTrials.gov Identifier: NCT04190862
• Recruitment Status: Recruiting
• First Posted: December 9, 2019
• Last Update Posted: December 9, 2019
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Angiocrine Bioscience
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anal Fistula	Drug: E-CEL UVEC	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 6 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Center, Investigator Initiated Phase 1B Trial of E-CEL UVEC as an Adjunct Cell Therapy for Treatment of Anal Fistulas
• Estimated Study Start Date: December 5, 2019
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety of dose escalation, as measured by incidence rate of treatment emergent adverse events following the administration of E-CEL UVEC [ Time Frame: 2 weeks ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: 6 weeks ]
   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.
2. 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 [ Time Frame: 24 weeks ]
   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.
3. Efficacy of E-CEL UVEC, as measured the rate of subjects presenting with relapse in treated fistula [ Time Frame: 6, 24 weeks after surgery ]
   Efficacy of E-CEL UVEC, as measured the rate of subjects presenting with relapse in treated fistula at week 6 and 24
4. Efficacy of E-CEL UVEC, as measured by time to complete healing of each side [ Time Frame: 24 weeks after surgery ]
   Efficacy of E-CEL UVEC, as measured by time to complete healing of each side of injection site

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Julianna Brouwer, MPH; 212-746-8539; jub2024@med.cornell.edu

Contact: Ashley Graham, BS; 646-962-4642; arg2005@med.cornell.edu

Locations

United States, New York

Weill Cornell Medical College - NewYork-Presbyterian Hospital; Recruiting

New York, New York, United States, 10065

Contact: Jeffrey W Milsom, MD 646-962-2270 jwm2001@med.cornell.edu

Contact: Julianna Brouwer, MPH 212-746-8539 jub2024@med.cornell.edu

Sub-Investigator: Heather Yeo, MD

Sub-Investigator: Parul Shukla, MD

Sub-Investigator: Kelly Garrett, MD

Sponsors and Collaborators

Weill Medical College of Cornell University

Angiocrine Bioscience

Investigators

• Principal Investigator: Jeffrey W Milsom, MD; Weill Medical College of Cornell University

More Information

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT04190862
• Other Study ID Numbers: 19-04020122
• First Posted: December 9, 2019
• Last Update Posted: December 9, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Rectal Fistula; Fistula; Pathological Conditions, Anatomical; Intestinal Fistula; Digestive System Fistula; Digestive System Diseases; Intestinal Diseases; Gastrointestinal Diseases; Rectal Diseases