E-CEL UVEC Treatment for Anal Fissures

Официальное название

An Open-Label, Single-Center, Investigator Initiated Phase 1B Trial of E-CEL UVEC Cell Therapy for the Treatment of Chronic Anal Fissure

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат E-CEL UVEC cells (AB-207)
  Allogeneic (consented-maternal donor) E4ORF1+ (pro-survival gene transduced) human umbilical vein endothelial cells (percutaneous injection formulation)

Первичные конечные точки

• Number of severe injection site reactions [Срок оценки: Up to 180 days]
• Number of severe injection site reactions that are serious adverse events related to IP [Срок оценки: Up to 180 days]
• Proportion of treated responders [Срок оценки: Up to 180 days]

Вторичные конечные точки (12)

• Changes in severity of pain on defecation (NRS) from (Day 0) baseline [Срок оценки: Days 0, 14, 21, 28, 42, 56, 90 and 180]
• Proportion of treated responders [Срок оценки: Days 14, 21, 28, 42, 56, 90 and 180]
• Change in proportion of subjects [Срок оценки: Days 0, 14, 21, 28, 42, 56, 90 and 180]
• Proportion of treated subjects who have complete cessation of fissure-related symptoms [Срок оценки: Up to 180 days]
• Median percent change in fissure-wound from baseline (Day 0) [Срок оценки: Days 0, 14, 21, 28, 42, 56, 90 and 180]
• Mean percent change in fissure-wound from baseline (Day 0) [Срок оценки: Days 0, 14, 21, 28, 42, 56, 90 and 180]
• Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) [Срок оценки: Day 14]
• Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) [Срок оценки: Day 21]
• Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) [Срок оценки: Day 28]
• Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) [Срок оценки: Day 42]
• Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) [Срок оценки: Day 56]
• Proportion of treated subjects who have ≥ 50% wound closure from baseline (Day 0) [Срок оценки: Day 90]

Критерии участия

Критерии включения

• Adults 18 years and older
• Anterior or posterior chronic anal fissure (CAF) - chronicity defined as presence of anal fissure ≥ 6 weeks
• Inadequate response to medical treatment of anal fissure (1 month of failed vasodilator treatment plus declined or failed botulinum injection treatment)
• Recent history of pain on defecation at a level 4 or higher on the numerical rating scale (NRS)
• 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%
• Willing to take adequate contraceptive measures
• Willing to sign an informed consent form and follow instructions for the trial including appearing for visits and filling out questionnaires

Критерии исключения

• Lateral anal fissure
• 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)
• Active, untreated or medically unresponsive infection of the anal fissure or fistula (e.g., erythema and pus)
• 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
• Presence of inflammatory bowel diseases (e.g., Crohn's, ulcerative colitis)
• Taking systemic chemotherapy or local pelvic radiation treatments
• Renal impairment defined by serum creatinine ≥ 1.5 x upper limit of normality (ULN)
• 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

• Active alcohol or substance use that, in the opinion of the site investigator, will interfere with study follow-up.
• Active malignant tumor (tumors must be in remission for ≥ 6 months without maintenance chemotherapy and/or radiation)
• Ongoing or recent history (within 6 months) of abnormal, severe, progressive, or uncontrolled hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases
• Congenital immunodeficiencies
• History of major surgery or severe trauma within the previous 3 months
• 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)
• Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during the study (180 days)
• Subjects who have known hypersensitivity or documented allergy to DMSO
• Subjects who do not wish to or cannot comply with study procedures

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Weill Cornell Medicine — New York

Идентификаторы

NCT: NCT06456073 · 23-11026760

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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