Filgotinib Alone and in Combination With Methotrexate (MTX) in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Are Naive to MTX Therapy
- Conditions
- Health Condition 1: M058- Other rheumatoid arthritis with rheumatoid factor
- Registration Number
- CTRI/2017/08/009474
- Lead Sponsor
- Gilead Sciences Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1) Male or female subjects who are greater than or equal to 18 years of age, on the day of signing informed consent.
2) Have a diagnosis of RA (2010 ACR/EULAR criteria) (Appendix 8), and are ACR functional class I-III
3) Have greater than or equal to 6 swollen joints (from a SJC66) and greater than or equal to 6 tender joints (from a TJC68) at both
Screening and Day 1 (need not be the same joints) (Appendix 7)
4) Must meet at least one of the following parameters at Screening:
a) Greater than or equal to 1 documented joint erosion on radiographs of the hands, wrists or feet by central
Reading
Or
b) positivity for either RF or anti-CCP Ab (based on central laboratory)
OR
c) Serum CRP greater than or equal to 4 mg/L (based on central laboratory)
5) Have limited or no prior treatment with MTX, ie, no more than 3 doses of MTX greater than or equal to 25 mg each in the subjectâ??s lifetime for the treatment of RA, with the last dose at least 28 days prior to Day 1, and are an appropriate candidate for MTX therapy, as per investigator judgment
6) Females of childbearing potential (as defined in Appendix 5) must have a negative pregnancy test at Screening and Day 1
7) 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 5
8) Lactating female subjects must agree to discontinue nursing from Screening through the end of their study participation.
9) Meet one of the following tuberculosis (TB) Screening criteria:
a) No evidence of active or latent TB:
I)A negative QuantiFERON® TB-Gold In-Tube test at Screening and
II)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
III)No history of either untreated or inadequately treated latent or active TB infection
b) Previously treated for TB: ie, if a subject has previously received an adequate course of
therapy as per local standard of care for either latent TB (9 months of isoniazid in a
location where rates of primary multi-drug resistant TB infections are greater than 5% or an
acceptable alternative regimen) or active TB (acceptable multi-drug regimen). In these
cases, no QuantiFERON® TB-Gold In-Tube test (or 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-tuberculosis treatment and provide
appropriate documentation.
c) 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 equivalent assay]) in which active TB has been ruled out and for which
appropriate, ongoing, prophylactic treatment for latent tuberculosis has been initiated
prior to the first administration of study medicatio
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Prior treatments for RA as follows:
a)Alkylating agents, eg, chlorambucil or cyclophosphamide, at any time
b)Previous treatment with any JAK inhibitor
c)Previous therapy with csDMARDs other than MTX or hydroxychloroquine
(eg, gold salts, cyclosporine, leflunomide, azathioprine, sulfasalazine or any other immunosuppressive).
NOTE: Subjects with prior exposure to csDMARD may be enrolled if the subject had limited exposure (less than 3 months of total exposure). Washout periods need to be satisfied per protocol (section 5.4).
d)Use of any licensed or investigational biologic DMARDs (eg, B-cell depleting agents, tumor necrosis factor (TNF) alpha inhibitors, and/or interleukin (IL)-1, IL-6, IL-17, IL-12/23 inhibitors, including but not limited to abatacept, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, secukinumab, ustekinumab or tocilizumab
2) Known hypersensitivity or allergy to study drug, its metabolites, or formulation excipients.
3) Known hypersensitivity or allergy to the MTX, its metabolites, or formulation excipients.
4) Oral steroids at a dose greater than 10 mg/day of prednisone (or equivalent) or a prescription for oral steroids which has changed within 4 weeks of Day 1.
5) Receipt of an intra-articular or other injectable corticosteroid within 4 weeks prior to Day 1.
6) Use of nonsteroidal anti-inflammatory drugs (NSAIDs) which have not been at a stable dose (defined as no change in prescription) for at least 2 weeks prior to Day 1. NOTE: subjects are permitted to take acetylsalicylic acid at a dose of greater than or equal to 325mg daily for cardiac prophylaxis, or occasional NSAIDs for non-RA indications (eg, headache).
7) Administration of a live/attenuated vaccine within 30 days from Day 1, or planned during the study.
8) 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 are excluded as outlined in 1d.
9) Have undergone surgical treatments for RA, including synovectomy or arthroplasty in greater than 4 joints
10) 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.
11) Have a history of major surgery (requiring regional block or general anesthesia) within the last 3 months prior to Screening or planned major surgery during the study.
Exclusion criteria for MRI substudy
1) Inability to undergo an MRI examination (e.g., presence of a pacemaker, defibrillator, or other contraindicated implanted metallic device, such as anterior interbody cages, aneurysm clip or pedicle screws, severe claustrophobia or weight greater than 350 lb)
2) Metallic pigment-containing tattoos in the area of examination
3) Known allergy to gadolinium-based contrast agents
4) Difficult peripheral intravascular access
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint is the proportion of subjects who achieve an ACR20 response at Week 24.Timepoint: The primary endpoint is the proportion of subjects who achieve an ACR20 response at Week 24.
- Secondary Outcome Measures
Name Time Method The key secondary endpoints are: <br/ ><br>Change from Baseline in the HAQ-DI score at Week 24 <br/ ><br>The proportion of subjects who achieve DAS28 (CRP)2.6 at Week 24 <br/ ><br>Change from Baseline in mTSS at Week 24Timepoint: Week 24