Clinical Trials

Inclusion Criteria:

• Must have the ability to understand and sign a written ICF, which must be obtained prior to initiation of study procedures.
• Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit.
• Females of childbearing potential (as defined in Appendix 7) must have a negative pregnancy test at screening and baseline.
• Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 7.
• Documented diagnosis of CD with a minimum disease duration of 3 months with involvement of the ileum and/or colon at a minimum, documented by the following:
  • Medical record documentation of, or an ileocolonoscopy (full colonoscopy with the intubation of terminal ileum) report dated ≥ 3 months before enrollment, which shows features consistent with CD, determined by the procedure performing physician; AND
  • Medical record documentation of or a histopathology report showing features consistent with CD, determined by the pathologist.
• Moderately or severely active CD as defined by:
  • CDAI total score between 220 and 450 inclusive; AND
  • PRO2 score consisting of abdominal pain ≥ 2 (on CDAI scale of 0 to 3) OR daily stool frequency ≥ 4; AND
  • Evidence of active disease as measured by SES-CD based on central reading:
    • Total score ≥ 6; OR
    • If disease is limited to the ileum and/or right colon, a combined score ≥ 4 in these two segments.
• Meet one of the following TB screening criteria:
  • No evidence of active or latent TB; i.e.,
    • A negative QuantiFERON® TB-Gold In-Tube test (or centrally reported equivalent assay) at screening; AND
    • A chest radiograph (views as per local guidelines) taken at screening or within the 3 months prior to screening (with the report or films available for investigator review) without evidence of active or latent TB infection; AND
    • No history of either untreated or inadequately treated latent or active TB infection.
  • Previously treated for TB; i.e., if a subject has previously received an adequate course of therapy as per local standard of care for either latent TB (e.g., 9 months of isoniazid in a location where rates of primary multi-drug resistant TB infections are < 5% or an acceptable alternative regimen) or active TB (acceptable multi-drug regimen). In these cases, no QuantiFERON® TB-Gold In-Tube test (or centrally reported equivalent assay) need be obtained, but a chest radiograph must be obtained if not done so within 3 months prior to screening (with the report or films available for investigator review). It is the responsibility of the investigator to verify the adequacy of previous anti-TB treatment and provide appropriate documentation.
  • Newly identified latent TB during screening: ie, a subject who has a newly identified positive diagnostic TB test result (defined as a positive QuantiFERON® TB Gold in Tube test [or centrally reported equivalent assay]) in which active TB has been ruled out and for which appropriate, ongoing, prophylactic treatment for latent TB has been initiated for a minimum of 4 weeks prior to the first administration of study medication. Adequate treatment for latent TB is defined according to local country guidelines for immunocompromised subjects. Quantiferon testing may not be repeated except in the case of a single repeat for indeterminate results.   
  • Cases falling under category “b” and “c” need to be approved by the Sponsor prior to enrollment in the study. No subject with currently ACTIVE TB may be enrolled in the study, regardless of past or present anti-TB medication use.
• Laboratory parameters (subjects who fail to meet below reference laboratory tests may be re-tested once at discretion of investigator prior to being considered a screen failure):
  • Hepatic panel (AST, ALT, total bilirubin) ≤ 2 times ULN;
  • Estimated CrCl ≥ 40 ml/min as calculated by the CC&G equation;
  • Hemoglobin ≥ 8 g/dL (both males and females);
  • Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1,500/mm^3);
  • Platelets ≥ 100 × 10^9/L;
  • White blood cells (WBC) ≥ 3.0 x 10^9/L;
  • Absolute lymphocyte count >750/mm^3.
• May be receiving the following drugs (subjects on these therapies must be willing to remain on stable doses for the noted times):
  • Oral 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must remain stable for the first 10 weeks after randomization;
  • Azathioprine or 6-MP or MTX provided the dose prescribed has been stable for 4 weeks prior to randomization; dose must remain stable for the first 10 weeks after randomization;
  • Oral corticosteroid therapy (prednisone prescribed at a stable dose ≤ 30 mg/day or budesonide prescribed at a stable dose of ≤ 9 mg/day) provided the dose prescribed has been stable for 2 weeks prior to randomization; dose must remain stable for the first 14 weeks after randomization;
  • Antibiotics for the treatment of CD (eg, metronidazole, ciprofloxacin) provided the dose prescribed has been stable for 2 weeks prior to randomization. Dose must remain stable for the first 10 weeks after randomization. Subjects who are on cyclic therapy must continue their standard low-dose regimen without change for the first 10 weeks after randomization.
• Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose.
• Must be up to date on colorectal cancer screening and surveillance as standard of care according to local guidelines.

Exclusion Criteria:

• Pregnant or lactating females.
• Males and females of reproductive potential who are unwilling to abide by protocol-specified contraceptive methods as defined by Appendix 7.
• Females who may wish to become pregnant and/or plan to undergo egg donation or egg harvesting for the purpose of current or future fertilization during the course of the study and up to 35 days after the last dose of the study drug.
• Male subjects unwilling to refrain from sperm donation during the study and for at least 90 days after the last dose of study drug.
• Known hypersensitivity to filgotinib, its metabolites, or formulation excipients.
• Currently have complications of CD as any of the following:
  • Symptomatic strictures; OR
  • Severe (impassable) rectal/anal stenosis; OR
  • Fistulae other than perianal fistulae; OR
  • Short bowel syndrome; OR
  • Any other complications which could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with filgotinib.
• Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to Day 1 and are not anticipated to require surgery.
• History of major surgery or trauma within 30 days prior to screening.
• Presence of UC, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon.
• History of total colectomy, subtotal colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study.
• Dependence on parenteral nutrition.
• History or evidence of incompletely resected colonic mucosal dysplasia.
• Stool sample positive for Clostridium difficile (C. diff) toxin, pathogenic Escherichia coli (E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp 14) Stool sample positive for ova and parasites test (O&P) unless approved by the medical monitor.
• Active clinically significant infection or any infection requiring hospitalization or treatment with intravenous anti-infectives within 30 days of screening (or 8 weeks of Day 1); or any infection requiring oral anti-infective therapy within 2 weeks of screening (or 6 weeks of Day 1).
• Infection with HIV, hepatitis B, or hepatitis C.
• Presence of Child-Pugh Class C hepatic impairment.
• Active TB or history of latent TB that has not been treated.
• History of malignancy within the last 5 years except for subjects who have been treated or resected for non-melanoma skin cancer or cervical carcinoma in situ.
• History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma.
• History of treatment with lymphocyte-depleting therapies, including but not limited to alemtuzumab, cyclophosphamide, total lymphoid irradiation, and rituximab.
• History of cytapheresis ≤ 2 months prior to screening.
• Use of any prohibited concomitant medications.
• Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) or psychiatric problem (including, but not limited to alcohol or drug abuse) that, in the opinion of the Investigator or Sponsor, would make the subject unsuitable for the study or would prevent compliance with the study protocol.
• Administration of a live or attenuated vaccine within 30 days of randomization.
• History of opportunistic infection or immunodeficiency syndrome.
• Currently on any chronic systemic (oral or intravenous) anti-infective therapy for chronic infection (such as pneumocystis (PCP), cytomegalovirus (CMV), herpes zoster, atypical mycobacteria).
• History of disseminated Staphylococcus aureus.
• History of symptomatic herpes zoster or herpes simplex within 12 weeks of screening, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or central nervous system zoster.