Clinical Trials List
Protocol NumberGS-US-417-0301
NCT Number(ClinicalTrials.gov Identfier)NCT02889796
2016-12-01 - 2021-12-31
Phase III
Terminated11
ICD-10M06.9
Rheumatoid arthritis, unspecified
ICD-10M06
Other rheumatoid arthritis
A Randomized, Double-blind, Placebo- and Active-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 52 weeks in Combination with Methotrexate to Subjects with Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
-
Trial Applicant
GILEAD SCIENCES HONG KONG LIMITED
-
Sponsor
GILEAD SCIENCES HONG KONG LIMITED, TAIWAN BRANCH
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
方耀凡
Co-Principal Investigator
- Ping-Han Tsai 無
- Chang-Fu Kuo 無
- 張哲慈 無
- Shue-Fen Lo 無
- 陳彥輔 無
- TianMing Zhan 無
The Actual Total Number of Participants Enrolled
3 Terminated
Audit
None
Co-Principal Investigator
- 郭佑民 無
- CHIEH-YU SHEN 無
- CHENG-HAN WU 無
- SONG-CHOU HSIEH 無
- CHIH-WEI YU 無
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Rheumatoid arthritis
Objectives
This is a randomized, double-blind, placebo- and active-controlled,Phase 3 study in adult male and female subjects with active RA who have an inadequate response to MTX (MTX-IR). The study is designed to evaluate the efficacy, safety, and tolerability of filgotinib as well as its effect on work productivity, fatigue, and quality of life.
Test Drug
Filgotinib
Active Ingredient
Filgotinib
Dosage Form
Tablet
Dosage
100 mg/Tablet、200 mg/Tablet
Endpoints
The primary endpoint is:
The proportion of subjects who achieve an ACR20 response at Week 12
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
The proportion of subjects who achieve DAS28 (CRP)<2.6 at Week 24
Change from Baseline in mTSS at Week 24
Other secondary endpoints include:
The proportion of subjects who achieve ACR50 and ACR70 at Weeks 4, 12, 24 and 52,
ACR20 at Weeks 4, 24, and 52, and ACR20/50/70 over time from Day 1 through Week 52
Change from Baseline in individual components of the ACR response at Weeks 4, 12, 24,
and 52 and over time from Day 1 through Week 52
The proportion of subjects who achieve change in HAQ-DI of ≥0.22 at Weeks 4, 12, 24, and
52, and over time from Day 1 through Week 52
Change from Baseline in DAS28 (CRP) at Weeks 4, 12, 24, and 52, and over time from
Day 1 through Week 52
The proportion of subjects who achieve DAS28 (CRP)≤3.2 at Weeks 4, 24, and 52, and over
time from Day 1 through Week 52
The proportion of subjects who achieve DAS28 (CRP)<2.6 at Weeks 4, 12, and 52, and over
time from Day 1 through Week 52
ACR-N and EULAR response at Weeks 4, 12, 24, and 52, and over time from Day 1 through
Week 52
Change from Baseline in CDAI at Weeks 4, 12, 24, and 52, and over time from Day 1
through Week 52
Change from Baseline in SDAI at Weeks 4, 12, 24, and 52, and over time from Day 1
through Week 24
Change from Baseline in the mTSS at Week 52
The proportion of subjects with no radiographic progression from Baseline at Week 24 and
52
Absolute value and change from Baseline in SF-36, FACIT-Fatigue, and the EQ-5D over
time at Weeks 4, 12, 24 and 52, and over time from Day 1 through Week 52
Absolute value and change from Baseline in WPAI-RA at Weeks 4, 12, 24, and 52, and over
time from Day 1 through Week 52
The proportion of subjects who achieve an ACR20 response at Week 12
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
The proportion of subjects who achieve DAS28 (CRP)<2.6 at Week 24
Change from Baseline in mTSS at Week 24
Other secondary endpoints include:
The proportion of subjects who achieve ACR50 and ACR70 at Weeks 4, 12, 24 and 52,
ACR20 at Weeks 4, 24, and 52, and ACR20/50/70 over time from Day 1 through Week 52
Change from Baseline in individual components of the ACR response at Weeks 4, 12, 24,
and 52 and over time from Day 1 through Week 52
The proportion of subjects who achieve change in HAQ-DI of ≥0.22 at Weeks 4, 12, 24, and
52, and over time from Day 1 through Week 52
Change from Baseline in DAS28 (CRP) at Weeks 4, 12, 24, and 52, and over time from
Day 1 through Week 52
The proportion of subjects who achieve DAS28 (CRP)≤3.2 at Weeks 4, 24, and 52, and over
time from Day 1 through Week 52
The proportion of subjects who achieve DAS28 (CRP)<2.6 at Weeks 4, 12, and 52, and over
time from Day 1 through Week 52
ACR-N and EULAR response at Weeks 4, 12, 24, and 52, and over time from Day 1 through
Week 52
Change from Baseline in CDAI at Weeks 4, 12, 24, and 52, and over time from Day 1
through Week 52
Change from Baseline in SDAI at Weeks 4, 12, 24, and 52, and over time from Day 1
through Week 24
Change from Baseline in the mTSS at Week 52
The proportion of subjects with no radiographic progression from Baseline at Week 24 and
52
Absolute value and change from Baseline in SF-36, FACIT-Fatigue, and the EQ-5D over
time at Weeks 4, 12, 24 and 52, and over time from Day 1 through Week 52
Absolute value and change from Baseline in WPAI-RA at Weeks 4, 12, 24, and 52, and over
time from Day 1 through Week 52
Inclution Criteria
1) Male or female subjects who are ≥18 years of age, on the day of signing informed consent. (In Taiwan, only subjects who are ≥20 years of age will be enrolled.)
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 both Screening and Day 1 (need not be the same joints).
4) Must meet at least one of the following parameters at Screening:
a) ≥1 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) ≥3 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 ≥ 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 a stably prescribed dose of 7.5-25 mg/weekly for at least 4 weeks prior to Day 1. Stable doses of <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 >25 mg weekly are not permitted during the study.
b) Subjects should be receiving an adequate and prescribed 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.
c) Subjects may use concomitant hydroxychloroquine (HCQ) ≤400 mg/day or chloroquine ≤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 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. You may ask your study doctor for detailed information.
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:
A negative QuantiFERON® TB-Gold In-Tube test 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
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 <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 medication. Adequate treatment for latent TB is defined according to local country guidelines for immunocompromised subjects.
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.
10) Able and willing to sign the informed consent as approved by the Research Ethics Committee (REC). Written consent must be provided before initiating any screening evaluations. Subjects must have read and understood the informed consent form (ICF), must fully understand the requirements of the study, and must be willing to comply with all study visits and assessments; subjects who cannot read or understand the ICF may not be enrolled by a guardian or any other individual.
11) Able and willing to perform subcutaneous self-injections or have a caregiver able, willing and available to administer the injections.
12) Subjects receiving non-prohibited medication for any reason should be be on a stable dose (defined as no change in prescription) within 7 days or 5 half-lives (whichever is longer) prior to the first administration of study drug on Day 1.
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 both Screening and Day 1 (need not be the same joints).
4) Must meet at least one of the following parameters at Screening:
a) ≥1 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) ≥3 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 ≥ 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 a stably prescribed dose of 7.5-25 mg/weekly for at least 4 weeks prior to Day 1. Stable doses of <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 >25 mg weekly are not permitted during the study.
b) Subjects should be receiving an adequate and prescribed 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.
c) Subjects may use concomitant hydroxychloroquine (HCQ) ≤400 mg/day or chloroquine ≤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 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. You may ask your study doctor for detailed information.
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:
A negative QuantiFERON® TB-Gold In-Tube test 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
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 <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 medication. Adequate treatment for latent TB is defined according to local country guidelines for immunocompromised subjects.
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.
10) Able and willing to sign the informed consent as approved by the Research Ethics Committee (REC). Written consent must be provided before initiating any screening evaluations. Subjects must have read and understood the informed consent form (ICF), must fully understand the requirements of the study, and must be willing to comply with all study visits and assessments; subjects who cannot read or understand the ICF may not be enrolled by a guardian or any other individual.
11) Able and willing to perform subcutaneous self-injections or have a caregiver able, willing and available to administer the injections.
12) Subjects receiving non-prohibited medication for any reason should be be on a stable dose (defined as no change in prescription) within 7 days or 5 half-lives (whichever is longer) prior to the first administration of study drug on Day 1.
Exclusion Criteria
1) Prior treatments for RA as follows:
a) Alkylating agents, eg chlorambucil or cyclophosphamide, at any time
b) Previous treatment with JAK inhibitor
c) Leflunomide use within 8 weeks prior to Day 1 or in the case of cholestyramine washout, within 4 weeks prior to Day 1
d) Discontinuation of hydroxychloroquine or chloroquine less than 4 weeks prior to Day 1
e) Cyclosporine, other calcineurin inhibitors, gold therapy, sulfasalazine, mycophenolate mofetil, or azathioprine within 4 weeks of Day 1 visit
f) Subjects that have failed prior therapy with a bDMARD are not eligible to participate. Subjects with prior exposure to one bDMARD may be enrolled (approximately 20% of total study population) if there is documented evidence of limited exposure (ie, less than 3 months) to the bDMARD
g) Any previous use of adalimumab
h) Any previous use of rituximab or other selective B lymphocyte depleting agents (including experimental agents)
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 (or 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 (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 ≤325mg daily for cardiac prophylaxis, or occasional NSAIDs for non-RA indications (eg, headache).
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
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 anesthesia) within the last 3 months 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, eg, generalized osteoarthritis, systemic inflammatory condition other than RA such as, but not limited to: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, inflammatory bowel disease associated arthropathies, systemic lupus erythematosus, scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, or gout. Subjects with any history of Felty’s syndrome or juvenile idiopathic arthritis are excluded, regardless of the disease activity level at Screening. (NOTE: subjects with concurrent Sjogren's syndrome or limited cutaneous vasculitis associated with RA are not excluded, and may be enrolled, based on investigator judgment).
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, 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.
I am aware that if the test result is found to be HIV positive during screening, my study doctor will report to regulatory authorities as required by law.
Signature of subject: ___________________ Date of Signature :______________________
19) Evidence of active Hepatitis C Virus (HCV) infection. Subjects with positive HCVAb at screening, require reflex testing for HCV RNA. Subjects with positive Hep C RNA viral load (VL) at screening will be excluded. Subjects with positive HCV Ab, but negative HCV RNA VL are eligible per investigator judgment, but require ongoing monitoring as outlined in the schedule of assessments. Subject with active HCV during the study, as evidenced by RNA positivity will be discontinued from study drug as outlined in the protocol.
20) Evidence of active Hepatitis B Virus (HBV) infection. Subjects with positive HBV surface antigen (HBsAg) at screening are excluded from the study. Subjects with positive HBV core Ab and negative HBsAg, require reflex testing for HBV DNA. Subjects with positive HBV DNA at screening will be excluded. Subjects with positive HBV core Ab, and negative HBV DNA are eligible per investigator judgment, but may require prophylactic treatment in accordance with HBV treatment guidelines/local standard of care and require ongoing monitoring with blood tests for HBV DNA every 3 months, as outlined in the schedule of assessments. Subject with evidence of active Hepatitis B during the study, as evidenced by RNA positivity, will be discontinued from study drug as outlined in the protocol.
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-infectives within 60 days of Screening; or any infection requiring oral anti‑infective therapy within 30 days of Screening.
23) Currently on any therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, and atypical mycobacteria). Past history of disseminated Staphylococcus aureus or disseminated Herpes simplex infection.
24) History of symptomatic herpes zoster infection within 12 weeks prior to Screening or have history of disseminated/complicated herpes zoster infection (multi dermatomal involvement, ophthalmic zoster, central nervous system involvement or postherpetic neuralgia)
25) History of an infected joint prosthesis or other implanted device with retention of the prosthesis or device in situ.
26) Current drug, tobacco or alcohol abuse, per investigator judgement.
27) Any known condition or contraindication as addressed in the local labeling for adalimumab and/or MTX that would preclude the subject from participating in this study.
28) Any condition including active fibromyalgia that based on the investigator’s opinion would make it difficult to appropriately assess RA activity for the purposes of this study.
29) Any condition or circumstances which in the opinion of the Investigator or Sponsor may make a subject unlikely or unable to complete the study or comply with study procedures and requirements.
30) Use of prohibited medication. You may ask your study doctor for detailed information.
31) Significant blood loss (>450 mL) or transfusion of any blood product within 12 weeks prior to Day 1.
32) Tests performed at the central laboratory at Screening that meet any of the criteria below (out of range lab values may be rechecked one time, after consultation with the sponsor or its designee , before subject is considered a screen-failure):
a) Hemoglobin <8.0 g/dL (International System of Units [SI]: <80 g/L);
b) White blood cells <3.0 x 103 cells/mm3 (SI: <3.0 x 109 cells/L);
c) Neutrophils <1.5 x 103 cells/mm3 (SI: <1.5 x 109 cells/L);
d) Lymphocytes <0.5 x 103 cells/mm3 (SI: <0.5 x 109 cells/L);
e) Platelets <100 x 103 cells/mm3 (SI: <100 x 109 cells/L);
f) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5x ULN;
g) Total bilirubin level ≥2x ULN unless the subject has been diagnosed with Gilbert’s disease and this is clearly documented;
h) Estimated creatinine clearance <40 mL/min based on the Cockroft Gault formula.
a) Alkylating agents, eg chlorambucil or cyclophosphamide, at any time
b) Previous treatment with JAK inhibitor
c) Leflunomide use within 8 weeks prior to Day 1 or in the case of cholestyramine washout, within 4 weeks prior to Day 1
d) Discontinuation of hydroxychloroquine or chloroquine less than 4 weeks prior to Day 1
e) Cyclosporine, other calcineurin inhibitors, gold therapy, sulfasalazine, mycophenolate mofetil, or azathioprine within 4 weeks of Day 1 visit
f) Subjects that have failed prior therapy with a bDMARD are not eligible to participate. Subjects with prior exposure to one bDMARD may be enrolled (approximately 20% of total study population) if there is documented evidence of limited exposure (ie, less than 3 months) to the bDMARD
g) Any previous use of adalimumab
h) Any previous use of rituximab or other selective B lymphocyte depleting agents (including experimental agents)
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 (or 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 (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 ≤325mg daily for cardiac prophylaxis, or occasional NSAIDs for non-RA indications (eg, headache).
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
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 anesthesia) within the last 3 months 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, eg, generalized osteoarthritis, systemic inflammatory condition other than RA such as, but not limited to: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, inflammatory bowel disease associated arthropathies, systemic lupus erythematosus, scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, or gout. Subjects with any history of Felty’s syndrome or juvenile idiopathic arthritis are excluded, regardless of the disease activity level at Screening. (NOTE: subjects with concurrent Sjogren's syndrome or limited cutaneous vasculitis associated with RA are not excluded, and may be enrolled, based on investigator judgment).
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, 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.
I am aware that if the test result is found to be HIV positive during screening, my study doctor will report to regulatory authorities as required by law.
Signature of subject: ___________________ Date of Signature :______________________
19) Evidence of active Hepatitis C Virus (HCV) infection. Subjects with positive HCVAb at screening, require reflex testing for HCV RNA. Subjects with positive Hep C RNA viral load (VL) at screening will be excluded. Subjects with positive HCV Ab, but negative HCV RNA VL are eligible per investigator judgment, but require ongoing monitoring as outlined in the schedule of assessments. Subject with active HCV during the study, as evidenced by RNA positivity will be discontinued from study drug as outlined in the protocol.
20) Evidence of active Hepatitis B Virus (HBV) infection. Subjects with positive HBV surface antigen (HBsAg) at screening are excluded from the study. Subjects with positive HBV core Ab and negative HBsAg, require reflex testing for HBV DNA. Subjects with positive HBV DNA at screening will be excluded. Subjects with positive HBV core Ab, and negative HBV DNA are eligible per investigator judgment, but may require prophylactic treatment in accordance with HBV treatment guidelines/local standard of care and require ongoing monitoring with blood tests for HBV DNA every 3 months, as outlined in the schedule of assessments. Subject with evidence of active Hepatitis B during the study, as evidenced by RNA positivity, will be discontinued from study drug as outlined in the protocol.
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-infectives within 60 days of Screening; or any infection requiring oral anti‑infective therapy within 30 days of Screening.
23) Currently on any therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, and atypical mycobacteria). Past history of disseminated Staphylococcus aureus or disseminated Herpes simplex infection.
24) History of symptomatic herpes zoster infection within 12 weeks prior to Screening or have history of disseminated/complicated herpes zoster infection (multi dermatomal involvement, ophthalmic zoster, central nervous system involvement or postherpetic neuralgia)
25) History of an infected joint prosthesis or other implanted device with retention of the prosthesis or device in situ.
26) Current drug, tobacco or alcohol abuse, per investigator judgement.
27) Any known condition or contraindication as addressed in the local labeling for adalimumab and/or MTX that would preclude the subject from participating in this study.
28) Any condition including active fibromyalgia that based on the investigator’s opinion would make it difficult to appropriately assess RA activity for the purposes of this study.
29) Any condition or circumstances which in the opinion of the Investigator or Sponsor may make a subject unlikely or unable to complete the study or comply with study procedures and requirements.
30) Use of prohibited medication. You may ask your study doctor for detailed information.
31) Significant blood loss (>450 mL) or transfusion of any blood product within 12 weeks prior to Day 1.
32) Tests performed at the central laboratory at Screening that meet any of the criteria below (out of range lab values may be rechecked one time, after consultation with the sponsor or its designee , before subject is considered a screen-failure):
a) Hemoglobin <8.0 g/dL (International System of Units [SI]: <80 g/L);
b) White blood cells <3.0 x 103 cells/mm3 (SI: <3.0 x 109 cells/L);
c) Neutrophils <1.5 x 103 cells/mm3 (SI: <1.5 x 109 cells/L);
d) Lymphocytes <0.5 x 103 cells/mm3 (SI: <0.5 x 109 cells/L);
e) Platelets <100 x 103 cells/mm3 (SI: <100 x 109 cells/L);
f) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5x ULN;
g) Total bilirubin level ≥2x ULN unless the subject has been diagnosed with Gilbert’s disease and this is clearly documented;
h) Estimated creatinine clearance <40 mL/min based on the Cockroft Gault formula.
The Estimated Number of Participants
-
Taiwan
50 participants
-
Global
1650 participants
