Eligibility Details:
Inclusion Criteria:
1. Signed informed consent.
2. Participants of either gender greater than or equal to (>=) 18 years and less than or
equal to (<=) 75 years of age.
3. Participants with CD diagnosed at least 6 months prior to Screening visit in
accordance with accepted clinical, endoscopic, histological and/or radiological
criteria.
4. Presence of complex perianal fistula(s) with a maximum of 2 internal openings and a
maximum of 3 external openings based on clinical assessment; a central reading of a
locally performed contrast enhanced (gadolinium) pelvic MRI will be performed to
confirm location of the fistula and potential associated perianal abscess(es).
Fistula(s) must have been draining for at least 6 weeks prior to Screening visit.
Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are
not allowed in this study. A complex perianal fistula is defined as a fistula that
meets one or more of the following criteria :
- High inter-sphincteric, high trans-sphincteric, extra-sphincteric or
suprasphincteric.
- Presence of >=2 external openings.
- Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm 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. Clinically controlled, nonactive or mildly active CD, during the last six months prior
to Screening visit with:
- A patient reported outcomes (PRO-2) score <14 at Screening, AND
- A colonoscopy documenting the absence of ulcers larger than 0.5 cm in the colonic
mucosa:
- If colonoscopy data are not available within 6 months prior to Screening:
- A simple endoscopic score for Crohn's Disease (SES-CD) <=6 with absence of rectal
ulcers larger than 0.5 cm must be documented in a colonoscopy performed at
Screening before randomization.
- If colonoscopy data are available within 6 months prior to Screening, the
following must be documented, otherwise a new colonoscopy (as above) will be
mandatory:
- The absence of ulcers larger than 0.5 cm in the colonic mucosa AND
- the improvement or no worsening in abdominal pain and/or in the diarrhea,
sustained for one week or more, since the last colonoscopy was performed in the
clinical records until Screening visit.
AND
o No hemoglobin decrease >=2.0 gram per deciliter (g/dL) or an unexplained rising
C-reactive protein (CRP), > 5.0 milligram per liter (mg/L) to a concentration above
the referenced upper limit of normal (ULN) (unless the rise is due to a known process
other than luminal Crohn's Disease), since the last colonoscopy was performed as
compared to results during the Screening visit.
AND
o no initiation or intensification of treatment with corticosteroids,
immunosuppressants or monoclonal antibodies (mAbs) dose regimen since the last
endoscopy up to Screening visit.
6. Participants whose perianal fistulas were previously treated and have shown an
inadequate response or a loss of response while they were receiving either an
immunosuppressive agent or tumour necrosis factor (TNF)-alpha antagonist or
vedolizumab or ustekinumab, or having documented intolerance to any of these
treatments administered at least at approved or recommended doses during the minimum
period mentioned:
- Immunosuppressive agents: at least 3 months treatment with azathioprine (2-3
milligram per kilogram per day [mg/kg/day]), 6-mercaptopurine (1-1.5 mg/kg/day),
or subcutaneous/intramuscular methotrexate (25 mg/week) prior to Screening for
the study.
- TNFalpha antagonists:
- Infliximab: at least 14 weeks treatment at the approved doses for induction
and/or maintenance in Crohn´s disease prior to screening for the study. For
induction: 1 intravenous dose of 5 milligram per kilogram (mg/kg) followed by the
same dose 2 and 6 weeks after. For maintenance: 5-10 mg/kg intravenously every 8
weeks, or more frequently.
- Adalimumab: at least 14 weeks treatment at the approved doses for induction
and/or maintenance in Crohn's disease prior to screening for the study. For
induction: 1 subcutaneous dose of 160 milligram (mg), followed by 80 mg 2 weeks
after. For maintenance: 40 mg subcutaneously every other week, or weekly.
- Certolizumab l: at least 14 weeks treatment at the approved doses for induction
and/or maintenance in Crohn´s disease prior to screening for the study. For
induction: 1 subcutaneous dose of 400 mg, followed by the same dose 2 and 4 weeks
after. For maintenance: 400 mg subcutaneously every 2 to 4 weeks.
- Anti-integrin: at least 14 weeks treatment of the approved dose for induction
and/or maintenance in Crohn´s disease prior to screening for the study. For
induction: Vedolizumab 300 mg. For maintenance: Vedolizumab 300 mg every 4 to 8
weeks.
- Anti-interleukin (IL)-12/23: at least 16 weeks treatment of the approved dose in
Crohn´s disease prior to screening for the study. For induction: Ustekinumab,
approximately 6mg/kg intravenously initially then followed by 90 mg
subcutaneously every 8 weeks.
7. Women of childbearing potential (WCBP) must have negative serum pregnancy test at
screening (sensitive to 25 international units [IU] human chorionic gonadotropin
[hCG]). Both WCBP or male participants participating in this study, with a WCBP as
partner, must agree to use an adequate method of contraception during the entire
duration of the study. An adequate method of contraception is defined as complete,
non-periodic sexual abstinence (refraining from heterosexual intercourse),
single-barrier method, vasectomy, adequate hormonal contraception (to have started at
least 7 days prior to Screening visit), or an intra-uterine device (to have been in
place for at least 2 months prior to Screening visit).
Exclusion Criteria:
1. Concomitant rectovaginal or rectovesical fistula(s).
2. Participant naïve to prior specific medical treatment for complex perianal fistula(s)
including immunosuppressant (IS) or anti-TNFs.
3. Presence of a perianal collection >2 cm in at least two dimensions on the central
reading MRI at Screening visit that was not adequately drained as confirmed by the
surgeon during the preparation procedure (week -3 to day 0).
4. Severe rectal and/or anal stenosis and/or severe proctitis (defined as the presence of
large >0.5 cm ulcers in the rectum) that make impossible to follow the surgery
procedure manual.
5. Participant with diverting stomas.
6. Active, uncontrolled infection requiring parenteral antibiotics.
7. Participant with ongoing systemic or rectal steroids for CD in the last 2 weeks prior
to the Preparation visit.
8. Participants with major alteration on any of the following laboratory tests or
increased risk for the surgical procedure:
- Serum creatinine levels >1.5 times the ULN
- Total bilirubin >1.5 ULN
- Aspartate Transaminase (AST)/ Alanine Transaminase (ALT) >3 times ULN
- Hemoglobin <10.0 g/dL
- Platelets <75.0*10^9/L
- Albuminemia <3.0 g/dL
9. Suspected or documented infectious enterocolitis within two weeks prior to Screening
visit.
10. Any prior invasive malignancy diagnosed within the last 5 years prior to Screening
visit. Participants with basal-cell carcinoma of the skin completely resected outside
the perineal region can be included.
11. Current or recent (within 6 months prior to the Screening visit) history of severe,
progressive, and/or uncontrolled hepatic, haematological, gastrointestinal (GI) (other
than CD), renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease
that may result in participants increased risk from study participation and/or lack of
compliance with study procedures.
12. Participants with primary sclerosing cholangitis.
13. Participants with known chronically active hepatopathy of any origin, including
cirrhosis and participants with persistent positive Hepatitis B Virus (HBV) surface
antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive
serology for Hepatitis C Virus (HCV) and quantitative HCV PCR within 6 months prior to
Screening.
14. Congenital or acquired immunodeficiencies, including participants known to be HIV
carriers
15. Known allergies or hypersensitivity to penicillin or aminoglycosides; Dulbecco
Modified Eagle's Medium (DMEM); bovine serum; local anaesthetics or gadolinium (MRI
contrast).
16. Contraindication to MRI scan (example, due to the presence of pacemakers, hip
replacements or severe claustrophobia).
17. Severe trauma within 6 months prior to Screening visit.
18. Pregnant or breastfeeding women.
19. Participants who do not wish to or cannot comply with study procedures.
20. Participants currently receiving, or having received any investigational drug within 3
months prior to Screening visit.
21. Participants previously treated with Cx601 or other allogeneic stem-cell therapy
cannot be enrolled into this clinical study.
22. Any major surgery of the GI tract (including one or more segments of the colon or
terminal ileum) within 6 months prior the screening or any minor surgery of the GI
tract within 3 months prior to screening.
23. Participants who had local perianal surgery other than drainage for the fistula within
6 months prior to the Screening visit, or those who may need surgery in the perianal
region for reasons other than fistulas at the time of inclusion in the study.
24. Contraindication to the anaesthetic procedure.
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