rheumatism Rheumatoid Arthritis
Conditions
Interventions
Filgotinib 200 mg group: filgotinib (200 mg once daily [q.d.]) + PTM filgotinib
100 mg (PTM q.d.) (N=141)
Filgotinib 100 mg group: filgotinib (100 mg q.d.) + PTM filgotinib 200 mg (PTM
q.d.) (N=141)
Rheumatism
Rheumatoid arthritis
Sponsors
Gilead Sciences
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: For a complete list of study inclusion and exclusion criteria, please refer to Sections 4.2.;1) Male or female subjects who are *18 years of age, on the day of signing informed consent.;2) Have a diagnosis of RA (2010 ACR/EULAR criteria for RA), and are ACR functional class I-III.;3) Have *6 swollen joints (from a SJC66) and *6 tender joints (from a TJC68) at Screening and Day 1;4) Have serum CRP * 4 mg/L based on central laboratory analysis at Screening;5) Ongoing treatment with a stable prescription of 1 or 2 csDMARD(s) as follows:;Permitted csDMARDs a) Use of MTX for at least 12 weeks prior to Day 1. Subject is on a stably prescribed dose and route of administration of 7.5-25 mg/weekly for at least 4 weeks prior to Day 1. Stable weekly doses 25 mg weekly are not permitted.;b) Subjects on MTX should be receiving an adequate and stable dose of folic acid (*5 mg/week total dose or as per local clinical practice) which should be confirmed or initiated at Screening, and continued throughout the study. MTX is not permitted to be used in combination with leflunomide.;c) Oral hydroxychloroquine *400 mg/day or chloroquine *250 mg/day with prescription having been stable for at least 4 weeks prior to Day 1;d) Oral sulfasalazine 1 g to 3 g/day with prescription having been stable for at least 4 weeks prior to Day 1;e) Oral leflunomide 10-20 mg/day, with prescription having been stable for at least 4 weeks prior to Day 1;The treatment with csDMARD should be continued at a stable dose until the end of the study. Dose adjustments are only permitted for the management of toxicity. Prior treatment with additional csDMARDs is allowed, however, subject may only be on 1 or 2 csDMARDs at Day 1 and appropriate wash out needs to be satisfied according protocol (Section 5.3), in order to be eligible for the study.;6) Have received at least one bDMARD for the treatment of RA to which they have had an inadequate response or intolerance. An inadequate response is defined as documented continued or recurrent disease activity after at least 12 weeks of treatment with any investigational or licensed bDMARD, including biosimilars, for the treatment of RA. Intolerance is defined as treatment discontinuation due to any documented adverse effect associated with a bDMARD used according to its respective label. There is no limit to the prior number of bDMARDs that may have been used by the subject, however the subject may not be on a bDMARD at Day 1 or during the study.
Exclusion criteria
Exclusion criteria: For a complete list of study exclusion criteria, please refer to study protocol (Sections 4.3):;1) Prior treatments for RA as defined in Section 4.3 of the protocol;2) Known hypersensitivity or allergy to the study drug(s), its metabolites, or formulation excipients.;3) Oral steroids at a dose >10 mg/day of prednisone equivalent or a prescription for oral steroids which has changed within 4 weeks of Day 1.;4) Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to Day 1.;5) Use of nonsteroidal anti-inflammatory drugs (NSAID(s) which have not been at a stable dose (defined as no change in prescription) for at least 2 weeks prior to Day 1. ;6) Administration of a live/ attenuated vaccine within 30 days prior to Day 1, or planned during the study.;7) Participation in any clinical study of an investigational drug/device within 4 weeks or 5 half-lives prior to Screening, whichever is longer. Exposure to investigational biologics should be discussed with the sponsor.;8) Have undergone surgical treatments for RA including synovectomy or arthroplasty in >4 joints and/or within the last 12 weeks prior to Screening;9) Have any chronic, uncontrolled medical condition, which would put the subject at increased risk during study participation, such as uncontrolled: diabetes, hypertension, morbid obesity, thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other disease of concern, as per judgment of investigator;10) Have a history of major surgery (requiring regional block or general anaesthesia) within the last 12 weeks prior to Screening or planned major surgery during the study.;11) Have a moderately to severely active, generalized musculoskeletal disorder that would interfere with assessment of study parameters or increase risk to the subject by participating in the study;12) Active autoimmune disease other than those listed above, that would interfere with assessment of study parameters or increase risk to the subject by participating in the study, eg, inflammatory bowel disease, uncontrolled thyroiditis, systemic vasculitis, transverse myelitis or uveitis.;13) History of or current moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), or within the last 6 months, a cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia or new or significant ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the investigator, would put the subject at risk by participation in the study. ;14) History of malignancy within the past 5 years prior to Screening (except for adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ with no evidence of recurrence). ;15) History of lymphoproliferative disease or current lymphoproliferative disease.;16) History of gastrointestinal perforation.;17) History of organ or bone marrow transplant. ;18) Positive serology for human immunodeficiency virus (HIV) 1 or 2;19) Evidence of active Hepatitis C Virus (HCV) infection;20) Evidence of active Hepatitis B Virus (HBV) infection. ;21) History of opportunistic infection or immunodeficiency syndrome which would put the subject at risk, as per investigator judgment.;22) Active infection that is clinically significant, as per judgment of the investigator, or any infection requiring hospitalization or treatment with intravenous anti-infe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Safety will be assessed by the documentation of AEs, clinical laboratory tests, physical examination, vital signs, and 12-lead ECGs during the study. Efficacy: The primary endpoint is the proportion of subjects who achieve an ACR20 response at Week 12. Pharmacokinetics: Plasma concentrations of filgotinib and its active metabolite (GS-829845) will be analyzed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: The key secondary endpoints are: The proportion of subjects who achieve DAS28 (CRP) *3.2 at Week 12 Change from baseline in the HAQ-DI score at Week 12 | — |
Countries
Argentina, Australia, Belgium, France, Germany, Hungary, Israel, Italy, Japan, Korea (the Republic of), Mexico, Spain, Switzerland, United Kingdom, United States of America
Outcome results
None listed