Chronic Anal Fissure
Conditions
Keywords
Chronic Anal Fissure
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. Improvement of CAF would be assessed in a standard, clinical manner (using brief digital palpation by the doctor), a method acceptable to the FDA, versus the original method (detailed quantitative photo-documentation). 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.
Interventions
BIOLOGICALE-CEL UVEC cells (AB-207)
Allogeneic (consented-maternal donor) E4ORF1+ (pro-survival gene transduced) human umbilical vein endothelial cells (percutaneous injection formulation)
Sponsors
Weill Medical College of Cornell University
Angiocrine Bioscience
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 defined as absence of the anal fissure with digital (e.g., index finger) palpation by investigator (supplemented by photo-documentation whenever possible) from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Proportion of treated responders | Days 14, 21, 28, 42, 56, 90 and 180 | Treated responders defined as absence of the anal fissure with digital (e.g., index finger) palpation by investigator (supplemented by photo-documentation whenever possible) from baseline (Day 0) |
| Change in proportion of subjects | Days 0, 14, 21, 28, 42, 56, 90 and 180 | Subjects with ≥ 50% reduction in pain-on-defecation (NRS) from baseline (Day 0) |
| Proportion of treated subjects who have complete cessation of fissure-related symptoms | Up to 180 days | — |
| 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 |
| 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 |
| Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) | Day 14 | — |
| 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). |
| 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. |
| Time-to 50% wound closure in days in subjects who achieved at least 50% wound closure | Up to 180 days | — |
| Time-to complete wound closure in days in subjects who achieved complete wound closure | Up to 80 | — |
| 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 |
| Percent of treatment-emergent adverse events per system organ class (SOC) | Up to 180 days | — |
| 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. |
| Time-to-relapse in days in subjects who experienced relapse | Up to 180 days | Days to relapse from time of healing. |
Countries
United States
Contacts
CONTACTKelly Garrett, MD
CONTACTKM Muktasid
PRINCIPAL_INVESTIGATORKelly Garrett, MD
Weill Medical College of Cornell University
Outcome results
None listed