| Eligibility |
Inclusion Criteria:
1. Male or female participants, between 18 and 65 years of age, who have a diagnosis of
moderately to severely active RA for at least 6 months as defined by at least 6
swollen joints (66 joint count) and at least 6 tender joints (68 joint count) at
Screening and Baseline (Day 1), and DAS28-CRP>3.2 at Screening. If a joint has both
swollen and tender symptoms, then the joint will be included in both the swollen
joints and tender joint categories.
2. Current treatment for RA:
1. Must be currently receiving and tolerating oral or parenteral MTX therapy at a
dose of 10 25 mg per week for at least 12 weeks prior to Day 1. The dose should
be stable for at least 4 weeks prior to Day 1. Patients must have had an
inadequate response to small molecule or biologic DMARD therapy.
2. Patients must be willing to receive oral folic acid (at least 5 mg/week or as per
local practice) or equivalent during the entire study (mandatory co-medication
for MTX treatment).
3. Inadequate response to biologic DMARDs: anakinra and etanercept must be withdrawn
at least 4 weeks prior to Day 1; tocilizumab must be withdrawn at least 12 weeks
prior to Day 1; other agents must be withdrawn at least 12 weeks or 5 half-lives
(whichever is longer) prior to Day 1.
4. Inadequate response to small molecule DMARDs (other than MTX): Leflunomide must
be withdrawn at least 8 weeks prior to Day 1 or a minimum of 2 weeks prior to Day
1 if after 11 days of standard cholestyramine washout. Lower than 400 mg/day of
oral hydroxychloroquine or lower than 250 mg/day of oral chloroquine is allowed,
but the dose should be stable for at least 12 weeks prior to Day 1 until Week 24
(if hydroxychloroquine or chloroquine have been discontinued, they must have been
withdrawn at least 4 weeks prior to Day 1). Other DMARDs must be withdrawn at
least 4 weeks prior to Day 1.
5. Tripterygium wilfordii: ongoing therapy is allowed, but the dose should be stable
for at least 12 weeks prior to Day 1 until Week 24; if discontinued, T.wilfordii
treatment must have been withdrawn at least 2 weeks prior to Day 1.
6. If receiving current treatment with oral corticosteroids, the dose must not
exceed 10 mg/day prednisolone or equivalent. During the 4 weeks prior to Baseline
(Day 1) the dose must remain stable until Week 24; if discontinued, oral
corticosteroids must have been withdrawn at least 2 weeks prior to Day 1.
7. Intra-articular and parenteral corticosteroids are not permitted within 6 weeks
prior to Baseline Day 1 and throughout the trial (until Week 24), with the
exception of IV administration of 100 mg methylprednisolone 30 minutes prior to
each infusion as this is part of the trial procedures.
8. Any concomitant non-steroidal anti-inflammatory drugs (NSAIDs) must be stable for
at least 2 weeks prior to Day 1; if discontinued, NSAIDs must have been withdrawn
at least 2 weeks prior to Day 1.
3. Males or females of child-bearing potential must agree to use an acceptable method of
contraception for 12 months following completion or discontinuation from the trial
(e.g., hormonal contraceptive, patch, intrauterine device, physical barrier).
Exclusion Criteria:
1. ACR functional Class IV or wheelchair/bed bound.
2. Primary or secondary immunodeficiency (history of, or currently active), including
known history of human immunodeficiency virus infection and Positive HIV.
3. Active tuberculosis (e.g., chest X-ray images of active tuberculosis); for those who
have used TNF-a antagonist or in the opinion of the investigator, QUANTIFERON®-TB GOLD
will be tested and the positive patients will be excluded.
4. Congestive heart failure (Class III or IV of New York Heart Association)
5. Interstitial lung disease (except mild).
6. Known allergies to mouse protein or other antibodies.
7. History of cancer including solid tumors, hematologic malignancies, and carcinoma in
situ (except participants with previous resected and cured basal or squamous cell
carcinoma, cervical atypical dysplasia, or in situ Grade I cervical cancer at least 1
year prior to the Screening Visit).
8. Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit
until Week 24.
9. Any disease or treatment (including biotherapy) that may bring unacceptable risk to
the subject, in the opinion of the investigator
10. Pregnant or lactating female subjects, or subjects who are planning to conceive or
breastfeed during the study period or within 12 months after the last administration.
11. History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive
arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or
other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory
bowel disease, pulmonary fibrosis, or Felty's syndrome, scleroderma, inflammatory
myopathy, mixed connective tissue disease, or any overlap syndrome).
12. Evidence of significant uncontrolled concomitant disease such as, but not limited to,
nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the
investigator's opinion, would preclude patient participation.
13. Positive anti-HCV antibodies at screening.
14. Positive anti-TP antibodies at screening.
15. Positive HBsAg or HBcAb, or HBV DNA =1×103 copies/mL at screening.
16. Any active infection (except nail bed fungal infection), or any serious infections
needed hospitalized or intravenous anti-infective treatment within 4 weeks before the
screening visit; or oral anti-infective therapy within 2 weeks before the screening
visit.
17. History of deep gap/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within
52 weeks prior to the screening visit.
18. Experienced serious or opportunistic infection in the recent 2 years in the opinion of
the investigator.
19. History of chronic infection (such as chronic pyelonephritis, bronchiectasis or
osteomyelitis)
20. Any congenital or acquired neurological disease, vascular disease or systemic disease,
especially joint pain and swelling (e.g., Parkinson's disease, cerebral palsy,
diabetic neuropathy) that may affect the effects assessment of this study.
21. History of alcohol abuse, drug abuse within 52 weeks prior to the screening visit
(judged by the investigator).
22. Received anti-integrin aV antibody or cell depletion therapy within 3 months or 5
half-lives (whichever is longer) prior to the screening visit.
23. Intolerant to glucocorticoid injection or has contraindication to glucocorticoid.
24. AST or ALT >2 times ULN. Or haemoglobin < 8.0 g/dL. Or absolute neutrophil count <
1.5x109/L. Or platelet count < 75x109/L.
25. Participated in any clinical study (within 12 weeks or within 5 half-lives of the
study drug, whichever is longer).
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