USTekinumab in Fistulising Perianal Crohn's Disease (USTAP)

Inclusion Criteria:

• Age ≥18 years

• Adults with moderate to severe Crohn's disease for at least six months

• Patients with at least one active perianal fistula track (between the anus or lowrectum and the perineum or vulva) confirmed by MRI within the previous 12 weeks

• Patients either naïve to anti-TNF therapy (50%) or refractory to anti-TNF therapy (50%).

• If female, subject is either not of child bearing potential, defined aspost-menopausal for at least1 year, surgically sterile (bilateral tubal ligation,bilateral oophorectomy or hysterectomy), or is of childbearing potential andpracticing one of the following methods of birth control during the study and for 150 days after the last dose:

• Condoms, sponge and foam, jellies with diaphragm or intrauterine device (IUD).IUDs may fail during azathioprine treatment. Alternative or additionalcontraceptive measures are advised, if azathioprine is initiated

• Oral or parenteral contraceptives for 3 months prior to study drugadministration

• A vasectomized partner

• Male subjects must agree to use an acceptable form of birth control, listed above atthe start of azathioprine administration and for 90 days after last dose ofazathioprine. Males should also commit to inform his partner(s) about it and toreport any pregnancy to the investigator.

• If female, subject is not breast-feeding throughout the study and for 150 days afterlast dose.

• Subjects or his/her legal representative have voluntarily signed and dated aninformed consent approved by and compliant with the requirements of this studyprotocol which has been approved by an Institutional Review Board (IRB)/IndependentEthics Committee (IEC)

• Adequate cardiac, renal and hepatic function as determined by the PrincipalInvestigator and demonstrated by Screening laboratory evaluations, questionnairesand physical examination results that do not indicate an abnormal clinical conditionwhich would place the subject at undue risk and thus preclude subject participationin the study

• Subject with a negative tuberculosis (TB) Screening Assessment [(including aPurified Protein Derivative (PPD) test < 5 mm and/or negative QuantiFERON-TB Goldtest or equivalent and negative Chest X-Ray (CXR) (PA and lateral view)] atscreening

Exclusion Criteria:

• Absence of written consent. People unable to give their consent (because of theirphysical or mental state)

• Pregnancy or breastfeeding

• Rectovaginal fistulas

• Rectal and/or anal stenosis

• Diverting stomas

• Abscess or collections >2 cm which are not properly drained ((i.e not drained atleast 3 weeks before baseline and adequately treated provided that there is noanticipated need for any further surgery)

• History of colectomy.

• History of colonic mucosal dysplasia or adenomatous colonic polyps that are notremoved.

• Screening stool trial positive for enteric pathogens or Clostridium difficile toxin.History of ongoing, chronic or recurrent infectious disease

• Positive HIV, Hepatitis B Virus (HBV),Hepatitis C Virus (HCV)

• Severe infection, chronic infection, history of recurrent infections, activeinfection including TB

• Malignancies or history of malignancies

• History of congestive heart failure (NYHA: Grade III and IV), demyelinating disease,current signs or history of severe/ progressive/uncontrolled renal, hepatic,endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, orsystemic lupus erythematosus (SLE).

• History of transplanted organ, lymphoproliferative disease, any known malignancy

• Previous allergy immunotherapy for anaphylaxis, hypersensitivity to ustekinumab orto any excipients, or metronidazole or ciprofloxacin

• Previous use of a biologic agent targeting Interleukin 12 (IL12) and/or Interleukin 23 (IL 23), including but not limited to ustekinumab

• Oral corticosteroids at a dose > 40 mg prednisone or its equivalent per day atinclusion (oral steroids should be at stable dose at least 7 days before inclusion)

• Any current or previous use of the following within 8 weeks before the first trialagent injection : cyclosporine, tacrolimus, anti-TNF biologic agents or other agentsintended to suppress or eliminate Tumor Necrosing Factor (TNF), and other biologics,including anti-integrin antibodies (approved or investigational), Janus Kinase (JAK)inhibitors (approved or investigational), or any current or previous use of aninvestigational agent

• Non-autologous stem cell therapy or biologic agents that deplete B or T cells <12months prior to baseline

• Current or recent (less than 4 weeks) vaccination with attenuated live vaccines

• Patients using a prohibited medication

• Patients participating in another trial or being in a follow-up period for anothertrial