E-CEL UVEC Cell Injection Treatment of Perianal Fistulas

Inclusion criteria

• Age 18 or older
• Willing and able to provide informed consent and medically eligible
• Diagnosed with perianal fistula per the following criteria:

• Diagnosis documented by physical/clinical examination and imaging specifically performed to assess the number and course of the perianal fistula tract---i.e., magnetic resonance imaging (MRI) and/or ultrasound
• Single tract without residual abscess cavity
• Low transsphincteric and intersphincteric fistulas that cross less than 30% of the external sphincter

i. Fistula internal opening width ≤ 3 mm. d. Maximum tract length of 10 cm e. Consistent with cryptoglandular origin f. Fistula-related pain of NRS < 3 (NRS 0-10) g. Absence of history of Crohn's disease, ulcerative colitis or other inflammatory bowel diseases

• For female patients of childbearing potential:

• A negative serum or urine pregnancy test at screening is required prior to enrollment
• Patient must be willing to use a highly effective method of contraception from the start of the screening period until at least 3 months after completion of last treatment
• For male patients who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception:

• Patient must be willing to use a recommended method of contraception and refrain from sperm donation from the start of screening period until for at least 3 months after completion of the last treatment

Exclusion criteria

• Concomitant rectovaginal fistulas
• Patients with an active abscess or suspicion of an active, untreated microabscess
• Presence of signs and symptoms suggestive or suspicious of an acute active infection or flare-up.
• Fistula-related pain measured as NRS ≥ 3 (NRS Scale 0-10) in the last 7 days.

• If the subject is eligible except for this exclusion criteria of fistula-related pain, then it is recommended that a loose seton be placed to reduce the fistula pain. In this particular situation, once the fistula-related pain is ≤ 2 on NRS (preferably 0 or 1), then the subject may be enrolled and the loose seton removed just prior to the 1st treatment with the investigational product.
• Presence of rectal and/or anal stenosis
• Presence of setons unless removed prior to the treatment
• Patients with known bleeding disorders.
• Patients with known risk factors for thrombus formation.
• Patients with overlying wound and skin infections.
• Patients with ongoing systemic steroid treatment or treated with steroids within the last 4 weeks prior to treatment
• 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 untreated alcohol or other addictive substance abuse in the 6 months prior to enrollment
• Active malignant tumor (tumors must be in complete remission for ≥ 6 months with completion of maintenance chemotherapy and/or radiation cycles), at least 6 months prior to first treatment
• Current recent history of abnormal, severe, progressive, uncontrolled hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases
• Congenital immunodeficiencies
• Major surgery or severe trauma within the previous 3 months
• Patients who are candidates for solid organ transplantation or who may have a high likelihood of needing a solid organ transplant (e.g., progressive heart failure)
• Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during the treatment regimen with investigational product (Arm A: 0-12 weeks; Arm B (with crossover): 0-24 weeks).
• Patients who have known hypersensitivity or documented allergy to dimethyl sulfoxide (DMSO)
• Patients who do not wish to or cannot comply with study procedures, including completion of all scheduled study visits and treatments
• Patients currently receiving, or having received any investigational drug within 6 months prior to E-CEL UVEC cell therapy