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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Allogeneic (consented-maternal donor) E4ORF1+ (pro-survival gene transduced) human umbilical vein endothelial cells (percutaneous injection formulation)
Weill Cornell Medicine
New York, New York, United States
RECRUITINGNumber of severe injection site reactions
Severe refers to Grade ≥ 3 as per CTCAE v5.0 terms and grading
Time frame: Up to 180 days
Number of severe injection site reactions that are serious adverse events related to IP
Time frame: Up to 180 days
Proportion of treated responders
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
Time frame: Up to 180 days
Changes in severity of pain on defecation (NRS) from (Day 0) baseline
Based on Numerical Rating Scale (NRS) measures at timepoints compared to baseline. Scale ranges from 0-10 with 0 representing no pain and severity of pain increasing chronologically.
Time frame: Days 0, 14, 21, 28, 42, 56, 90 and 180
Change in proportion of treated responders
Treated responders are defined as ≥ 50% reduction in pain-on defecation (using numerical rating scale (NRS)) and ≥ 50% reduction in fissure-wound-area (mm2) from baseline (Day 0)
Time frame: Days 0, 14, 21, 28, 42, 56, 90 and 180
Proportion of treated subjects who have complete cessation of fissure-related symptoms
Time frame: Up to 180 days
Median percent change in fissure-wound from baseline (Day 0)
Median percent change in fissure wound size based on mm\^2 using digital photo-image analysis
Time frame: Days 0, 14, 21, 28, 42, 56, 90 and 180
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Mean percent change in fissure-wound from baseline (Day 0)
Mean percent change in fissure wound size based on mm\^2 using digital photo-image analysis
Time frame: Days 0, 14, 21, 28, 42, 56, 90 and 180
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 14
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 21
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 28
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 42
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 56
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 90
Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0)
Time frame: Day 180
Time-to-response in days in treated responders
Treated responders are defined as those with ≥50% reduction in pain on defecation (using numerical rating scale (NRS)) and ≥50% reduction in fissure-wound area from baseline (Day 0).
Time frame: Up to 180 days
Time-to symptom improvement in days in treated subjects who achieved symptom improvement
Symptom improvement is defined as a minimum 50% reduction in pain-on defecation (using numerical rating scale (NRS)) in treated subjects.
Time frame: Up to 180 days
Time-to 50% wound closure in days in subjects who achieved at least 50% wound closure
Time frame: Up to 180 days
Time-to complete wound closure in days in subjects who achieved complete wound closure
Time frame: Up to 80
Cumulative number of severe adverse events, defined and graded by NCI CTCAE v5.0
Time frame: Up to 180 days
Percent of serious adverse events, including relatedness category
Percent of SAE and relatedness categories of SAE as defined and graded by NCI CTCAE v5.0
Time frame: Up to 180 days
Percent of treatment-emergent adverse events per system organ class (SOC)
Time frame: Up to 180 days
Proportion of fissure relapse in treated subjects
Fissure relapse is defined as worsening of pain and increase in size after healing.
Time frame: Up to 180 days
Time-to-relapse in days in subjects who experienced relapse
Days to relapse from time of healing.
Time frame: Up to 180 days