Amendment 1: •Updated projected study centers based on recent site selection metrics •Added a secondary objective for the evaluation of proctitis remission • Updates made to 3 exploratory objectives •Added randomization stratum of proctitis status •Removed inclusion criterion of perianal CDAI(PDAI)>4 •Clarified inclusion criterion around the acceptability of non-perianal fistulae and concurrent noncutting perianal seton(s) removal prior to randomization •Added inclusion of participants that had previously demonstrated treatment failure to a 4-week regimen of antibiotics for the treatment of perianal fistulae •Removed corticosteroids and vedolizumab from the inclusion criterion for defining participants as inadequate clinical responders •Updated to clarify that administration of stable doses of permitted concomitant medications was mandatory •Extended requirement for stable doses of corticosteroid therapy prior to randomization •Decreased the maximum dose permitted for prednisone (or equivalent) •Removed inclusion criterion around participant willingness and ability to take antibiotic treatment for perianal fistulizing Crohn’s disease (CD) and > 3 draining fistula of any type •Updated exclusionary CD activity index (CDAI) value •Clarified that participants must have an intact rectum in order to assess active proctitis at baseline •Added flexible sigmoidoscopy procedure and Simple Endoscopic Score (SES)-CD scoring •Clarified LTE study eligibility requirements for participants who met responder criteria •Added text to clarify when study and/or study drug discontinuation was mandatory •Added a data monitoring committee •Updated table of definitions to include all new definitions in alignment with changes to the objectives of the study •Updated background section of the protocol, including rationale for this study •Added a secondary efficacy end point of the proportion of participants achieving proctitis remission at Week 24

Amendment 2: • Added ClinicalTrials.gov identifier • Updated secondary objectives and end points to eliminate redundancy • Added study duration • Updated background information with emerging relevant clinical data and to ensure consistency with Edition 12 of the Investigator’s Brochure for filgotinib • Added formula for creatinine clearance calculation • Updated biomarker language to align with Gilead’s current protocol template • Updated inclusion criterion to clarify that QuantiFERON TB testing could not be repeated except in the case of a single repeat for indeterminate results • Added a new inclusion criterion to ensure standard of care colorectal cancer screening for patient population • Updated Exclusion 7 to remove tattoo as a contraindication to MRI examination • Updated exclusion criteria to clarify the required washout period before entry of participants who had been previously treated with ustekinumab • Added guidance for missed doses • Added guidance for initiation of new induction therapies prior to screening • Added instructions for budesonide taper • Added detailed descriptions of key assessments • Updated safety reporting language to align with Gilead’s current protocol template • Added wording to the informed consent process to ensure investigators counseled male participants on the associated risks of male infertility • Removed PDAI from screening • Added urinalysis to Week 24 • Separated fasting lipids from serum chemistry • Defined the duration of fasting • Removed fasting requirement from screening • Appendix 9 updated based on findings of drug-drug interaction study for filgotinib and hormonal contraceptives and to clarify the definitions of childbearing potential

Amendment 3: • Further clarified the eligible participant population via updates to study inclusion/exclusion criteria • Ensured study end points were evaluable for early terminating participants by addition of assessments at the early termination (ET) visit • Updated study director and medical monitor contact information • Updated Data Monitoring Committee meeting schedule to reflect the committee charter

Amendment 4: • Incorporated criteria for the assessment of non-response of perianal fistulae using patient reported symptom subscores of the PDAI • Allowed the concurrent use of vedolizumab therapy • Expanded the definition of dual refractory male participants in the United States • Replaced a stratification factor • Added an interim futility analysis for efficacy • Clarified that endoscopic assessment of anal canal was being conducted as part of the centrally read flexible sigmoidoscopy • Added a new exploratory objective for the study • Added a new exploratory end point for the study

Amendment 5: • Included additional criteria for luminal disease non-response • Included discontinuation criteria for thromboembolic events at the request of the United States Food and Drug Administration (US FDA) • Included a criterion to trigger an ad hoc DMC meeting at the request of the US FDA • Described a cardiovascular safety end point adjudication committee (CVEAC) that Gilead established at the request of the FDA • Included new guidance for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) screening and surveillance