Inclusion Criteria:
1. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.
2. The participant signs and dates a written, informed consent form (ICF) and any
required privacy authorization before the initiation of any study procedures.
3. The participant is male or female and aged 18 years or older.
4. The participant has complex perianal fistula(s) with a maximum of 2 internal openings
and a maximum of 3 external openings based on clinical assessment and a reading of a
locally-performed contrast enhanced (gadolinium) pelvic MRI. Fistula(s) must have been
draining for at least 6 weeks prior to baseline visit. A complex perianal fistula is
defined as a fistula that meets 1 or more of the following criteria:
1. High inter-sphincteric, high trans-sphincteric, extra-sphincteric or
suprasphincteric.
2. Presence of ≥2 external openings.
3. Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm in at
least 2 dimensions on MRI must be confirmed to have been drained adequately by
the surgeon during the preparation curettage in order to be eligible.
5. The participant has already received treatment with darvadstrocel for a complex
perianal fistula at least 6 months prior to baseline visit for retreatment, and their
physician has planned a repeat treatment administration for the original tract (full
remission not obtained or relapse of fistula draining) or for a new complex perianal
fistula tract.
6. The participant has controlled or mildly active CD (defined as patient reported
outcomes measure derived from CDAI patient reported outcome score-2 [PRO-2] score
<14).
7. A male participant who is nonsterilized and sexually active with a female partner of
childbearing potential agrees to use barrier method of contraception (e.g. condom with
or without spermicide) from signing of informed consent and until 1 year after repeat
administration.
8. A female participant of childbearing potential who is sexually active with a
nonsterilized male partner agrees to use a highly effective/effective method of
contraception from signing of informed consent and until 1 year after repeat
administration.
Exclusion Criteria:
1. The participant has lack of clinical response to prior treatment with darvadstrocel,
where clinical response is defined as closure of at least 50% of all treated external
fistula openings that were draining at baseline despite gentle finger compression or
in the case of a unique fistula, a partial closure of the fistula.
2. The participant has a history of hypersensitivity or allergies to darvadstrocel or
related compounds.
3. The participant has a history of hypersensitivity or allergies to penicillin or
aminoglycosides; Dulbecco modified eagle medium; bovine serum; local anesthetics or
gadolinium.
4. The participant is currently participating in a double-blind clinical study with
darvadstrocel. Participants participating in the ongoing INSPIRE registry
(Alofisel-5003) study would need to withdraw from that study in order to enroll in
this study.
5. The participant is currently receiving or has received any other investigational
medicinal product (IMP) within the last 3 months or at least 5 times the respective
elimination half-life time, whichever is longer, before signing the ICF.
6. The participant has known or suspected COVID-19 by the investigator within the past 2
months (additional testing may be performed at the discretion of the investigator).
Positive antibody testing for COVID without other evidence of current or recent active
infection does not exclude participation.
a) Participants who were in screening at the time that COVID 19-related factors
resulted in discontinuation may also be rescreened with approval of the sponsor or
designee.
7. The participant has major alterations in any of the following laboratory tests:
1. Serum creatinine levels >1.5 times the upper limit of normal (ULN).
2. Total bilirubin >1.5 × ULN.
3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3.0 × ULN.
4. Hemoglobin <10.0 g/dL.
5. Platelets <75.0 × 109/L.
6. Albumin <3.0 g/dL.
8. The participant has an increased risk for surgical procedure.
9. The participant has a known chronically active hepatopathy of any origin, including
cirrhosis and participants with persistent positive hepatitis B surface antigen and
quantitative hepatitis B virus polymerase chain reaction (PCR) or positive serology
for hepatitis C virus (HCV) and quantitative HCV PCR within 6 months before the
baseline visit.
10. If female, the participant is pregnant or breastfeeding, or intending to become
pregnant before participating in this study, during the study, or intending to donate
ova during such time period.
11. If male, the participant intends to donate sperm during this study.
12. The participant has a contraindication to MRI scan (e.g., due to the presence of
pacemaker, hip replacement, severe claustrophobia, or renal insufficiency as defined
by local clinical guidelines).
13. The participant has a contraindication to the anesthetic procedure.
14. The participant has severe rectal and/or anal stenosis that would make it impossible
to follow the surgery procedure.
15. The participant has severe proctitis (rectal ulcers >0.5 cm) that would make it
impossible to follow the surgery procedure.
16. The participant has any prior invasive malignancy diagnosed within the last 3 years
before baseline visit. Participants with basal cell carcinoma of the skin completely
resected outside the perineal region can be included.
17. The participant has a current or recent (within 6 months before the baseline visit)
history of severe, progressive, and/or uncontrolled hepatic, hematologic,
gastrointestinal (other than CD), renal, endocrine, pulmonary, cardiac, neurologic, or
psychiatric disease that may result in participant's increased risk from study
participation and/or lack of compliance with study procedures.
18. The participant has had major surgery of the gastrointestinal tract within 6 months
before baseline or any minor surgery of the gastrointestinal tract 3 months before
baseline.
19. The participant had local major perianal surgery, and/or treatment with darvadstrocel
within 6 months before baseline. The abscess drainage, cleaning surgery, or seton
placement are not considered as "local major surgery" in this protocol.
20. The participant does not wish to or cannot comply with study procedures.
