A Double Blind, Randomized Controlled Study, Evaluating the Safety and Efficacy of RD2 Ver.02 For the Management of Anal Fistulas

Inclusion criteria

• Subject is ≥18 years of age
• Subject has a transsphincteric or long intersphincteric anal fistula (>1.5 cm), with a seton in place for a minimum of 1 month, deemed eligible for primary or repeat fistula repair by anorectal advancement flap or LIFT: Anterior, posterior or lateral fistula, first or recurrent, at any position circumferentially, with one external opening and one internal opening.
• Subjects is unable or unwilling to receive invasive surgical procedures, anorectal advancement flap or LIFT procedure, and is opting for minimally invasive technique of anal fistula management (i.e., fistula tract debridement and suturing of internal opening).
• 2.1.4 Prior to enrollment, during the preceding 3 months from Treatment Visit, subject must undergo a pelvic MRI to evaluate eligibility criteria unable to be assessed clinically.
• Female subjects who are capable of conceiving and all males capable of insemination must use an acceptable form of contraception in order to participate in the study and for 6 months following study procedure (acceptable forms of contraception include condoms for males and contraceptive pills or IUDs for women)

Exclusion criteria

• Subject who has a life expectancy of less than 24 months.
• Subjects who are cognitively impaired and have a healthcare proxy or those who are cognitively impaired and clearly do not understand the contents of the informed consent form.
• Cannot withdraw blood in the required amount (up to 15 mL).
• Women who are pregnant or currently breast feeding.
• Subject is currently receiving (i.e., within the past 30 days) or scheduled to receive systemic steroids (more than 10mg per day).
• Multiple fistula tracts, as confirmed on pelvic MRI
• Short fistula tract that in the surgeon's opinion are amenable to fistulotomy
• Active infection including perianal infection, and/or any active systemic or local infection.
• Presence of a perirectal abscess on pelvic MRI
• Presence of dominant luminal active Crohn's disease, validated by recent colonoscopy from preceding 12 months, requiring immediate therapy
• Rectal and/or anal stenosis and / or active proctitis, if this means a limitation for any surgical procedure.
• Known allergies or hypersensitivity to any of the following: antibiotics including but not limited to penicillin, streptomycin, gentamicin, aminoglycosides; Human Serum Albumin (HSA); Dulbecco Modified Eagle's Medium (DMEM); materials of bovine origin; local anaesthetics or gadolinium (MRI contrast); Known hypersensitivity to reagents and components of RD2 Ver.02 including calcium gluconate, Kaolin or citrate and ethylene oxide.
• Contraindication to MRI scan, (e.g., due to the presence of pacemakers, hip replacements, or severe claustrophobia).
• Known coagulation problems, abnormal thrombocytes level or if heparin is given intravenously. Subjects who are taking Coumadin, Aspirin, Plavix (Clopidogrel), Eliquis or Pradaxa will not be excluded.
• Patients with increased risk for the surgical procedure or major alteration of any of the following laboratory tests:

• Serum Creatinine levels >1.5 times the upper limit of normality (ULN)
• Total bilirubin >1.5 times the ULN (unless predominantly non conjugated due to documented history of Gilbert's syndrome)
• AST/ ALT >3.0 times the ULN
• Hemoglobin <10.0 g/dL
• Platelets <150.0 x109/L
• Albuminemia <3.0 g/dL.
• Patients who do not wish to or cannot comply with study procedures.
• Patients currently receiving or having received within 12 months prior to enrolment into this clinical study, any investigational drug.
• Subjects who need surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study, or for whom such surgery is foreseen in this region in the 24 weeks after treatment administration.
• Contraindication to the anesthetic procedure.
• Subject with a diagnosis of Ulcerative Colitis
• Subject with malignancy, undergoing active treatment
• Rectovaginal fistula
• History of pelvic radiation