Filgotinib in Combination With Methotrexate in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
- Conditions
- Health Condition 1: M058- Other rheumatoid arthritis with rheumatoid factor
- Registration Number
- CTRI/2017/08/009478
- 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 for RA) (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 to1 documented joint erosion on radiographs of the hands, wrists or feet by central
reading AND positive result for anti-CCP Ab or RF (based on central laboratory),
OR
b) Greater than or equal to3 documented erosions on radiographs of the hands, wrists or feet by central reading if both antibodies (ie, RF, anti-CCP) are negative (based on central laboratory),
OR
c) Serum CRP greater than or equal to 6 mg/L (based on central laboratory)
5) Ongoing treatment with a stable dose of MTX as described below:
a) Use of oral MTX on a continuous basis for at least 12 weeks prior to Day 1 and on astably prescribed dose of 7.5-25 mg/weekly for at least 4 weeks prior to Day 1. Stable doses of greater than 7.5 mg/week are allowed only in the presence of intolerance or toxicity to higher doses or where higher doses are prohibited by the local label or local clinical practice. Doses greater than25 mg weekly are not permitted during the study.
b) Subjects should be receiving an adequate and prescribed stable dose of folic acid
( greater than or equal to 5 mg/week total dose or as per local clinical practice) which should be confirmed or initiated at Screening, and continued throughout the study.
c) Subjects may use concomitant hydroxychloroquine (HCQ) greater than or equal to 400 mg/day or chloroquine greater than or equal to 250 mg/day during the study with the prescription having been stable for at least 4 weeks prior to Day 1.
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:
o A negative QuantiFERON® TB-Gold In-Tube test at Screening and
o 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
o 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 mult
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
Prior treatments for RA as follows:
Alkylating agents, eg, chlorambucil or cyclophosphamide, at any time
Previous treatment with any JAK inhibitor
Previous therapy with csDMARDs other than MTX or hydroxychloroquine
(eg, gold salts, cyclosporine, leflunomide, azathioprine, sulfasalazine or any other immunosuppressive).
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
) Known hypersensitivity or allergy to study drug, its metabolites, or formulation excipients.
Known hypersensitivity or allergy to the MTX, its metabolites, or formulation excipients.
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.
Receipt of an intra-articular or other injectable corticosteroid within 4 weeks prior to Day 1.
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
Administration of a live/attenuated vaccine within 30 days from Day 1, or planned during the study.
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.
Have undergone surgical treatments for RA, including synovectomy or arthroplasty in greater than 4 joints
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.
MRI Sub-Study Criteria
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 12Timepoint: Week 12
- Secondary Outcome Measures
Name Time Method The key secondary endpoints are: <br/ ><br>1. The proportion of subjects who achieve DAS28 (CRP)â?¤3.2 at Week 12 <br/ ><br>2. Change from Baseline in the HAQ-DI score at Week 12 <br/ ><br>3. The proportion of subjects who achieve DAS28 (CRP)2.6 at Week 24 <br/ ><br>4. Change from Baseline in mTSS at Week 24Timepoint: Week 12, Week 24