E-CEL UVEC Treatment for Anal Fissures

Phase 1

Recruiting

• Conditions: Chronic Anal Fissure
• Interventions: Biological: E-CEL UVEC cells (AB-207)

• Registration Number: NCT06456073
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2024-06-06
• Study First Submitted QC: 2024-06-06
• Study First Posted: 2024-06-13
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-16
• Last Update Posted: 2024-08-19
• Study Start: 2024-09
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Adults 18 years and older

2. Anterior or posterior chronic anal fissure (CAF) - chronicity defined as presence of anal fissure ≥ 6 weeks

3. Inadequate response to medical treatment of anal fissure (1 month of failed vasodilator treatment plus declined or failed botulinum injection treatment)

4. Recent history of pain on defecation at a level 4 or higher on the numerical rating scale (NRS)

5. Vital signs upon screening:

   • Blood pressure: systolic ≥ 90 and < 140; and diastolic ≥ 60 and < 90.
   • 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%

6. Willing to take adequate contraceptive measures

7. Willing to sign an informed consent form and follow instructions for the trial including appearing for visits and filling out questionnaires

Exclusion Criteria

1. Lateral anal fissure

2. 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)

3. Active, untreated or medically unresponsive infection of the anal fissure or fistula (e.g., erythema and pus)

4. 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

5. Presence of inflammatory bowel diseases (e.g., Crohn's, ulcerative colitis)

6. Taking systemic chemotherapy or local pelvic radiation treatments

7. Renal impairment defined by serum creatinine ≥ 1.5 x upper limit of normality (ULN)

8. 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

9. Active alcohol or substance use that, in the opinion of the site investigator, will interfere with study follow-up.

10. Active malignant tumor (tumors must be in remission for ≥ 6 months without maintenance chemotherapy and/or radiation)

11. Ongoing or recent history (within 6 months) of abnormal, severe, progressive, or uncontrolled hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases

12. Congenital immunodeficiencies

13. History of major surgery or severe trauma within the previous 3 months

14. 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)

15. Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during the study (180 days)

16. Subjects who have known hypersensitivity or documented allergy to DMSO

17. Subjects who do not wish to or cannot comply with study procedures

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention Arm	E-CEL UVEC cells (AB-207)	Local percutaneous injection of E-CEL UVEC cells around the anal fissure

Primary Outcome Measures

Name	Time	Method
Number of severe injection site reactions	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	Up to 180 days
Proportion of treated responders	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

Secondary Outcome Measures

Name	Time	Method
Change in proportion of treated responders	Days 0, 14, 21, 28, 42, 56, 90 and 180	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-to-response in days in treated responders	Up to 180 days	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).
Changes in severity of pain on defecation (NRS) from (Day 0) baseline	Days 0, 14, 21, 28, 42, 56, 90 and 180	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-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	Percent of SAE and relatedness categories of SAE as defined and graded by NCI CTCAE v5.0
Time-to-relapse in days in subjects who experienced relapse	Up to 180 days	Days to relapse from time of healing.
Mean percent change in fissure-wound from baseline (Day 0)	Days 0, 14, 21, 28, 42, 56, 90 and 180	Mean percent change in fissure wound size based on mm\^2 using digital photo-image analysis
Median percent change in fissure-wound from baseline (Day 0)	Days 0, 14, 21, 28, 42, 56, 90 and 180	Median percent change in fissure wound size based on mm\^2 using digital photo-image analysis
Proportion of fissure relapse in treated subjects	Up to 180 days	Fissure relapse is defined as worsening of pain and increase in size after healing.
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	Symptom improvement is defined as a minimum 50% reduction in pain-on defecation (using numerical rating scale (NRS)) in treated subjects.

Trial Locations

Locations (1)

Weill Cornell Medicine; 🇺🇸 New York, New York, United States