| Eligibility |
Inclusion Criteria:
1. Male or female subjects, aged 18-75 years inclusive, with stable RA based on American
College of Rheumatology (ACR) criteria (see section 11.3) for at least 3 months
(subjects do not need to have active RA for Stage A of the study);
2. Subjects must have been on a stable dose of methotrexate (7.5 to 25 mg/week) taken
orally, subcutaneously, or intramuscularly, but not intravenously, for = 8 weeks prior
to randomization;
3. If a subject is also taking sulfasalazine or hydroxychloroquine, the subject must have
been on a stable dose of these medications for at least 8 weeks prior to
randomization;
4. If a subject is on corticosteroid therapy, the dose must not exceed 10 mg prednisone
or equivalent and the subject must have been on a stable dose for at least 4 weeks
prior to randomization;
5. Willing and able to give written Informed Consent and to comply with the requirements
of the study protocol;
6. Negative result of the human immunodeficiency virus (HIV) screen, the hepatitis B
screen, and the hepatitis C screen;
7. Judged to be otherwise healthy by the Investigator, based on medical history, physical
examination (including electrocardiogram [ECG]), and clinical laboratory assessments;
8. Female subjects of childbearing potential, and male subjects with partners of
childbearing potential, may participate if adequate contraception is used during, and
for at least the four weeks after, any administration of study medication. Adequate
contraception is defined as usage by at least one of the partners of a barrier method
of contraception, together with usage by the female partner, commencing at least three
months prior to Screening, of a stable regimen of any form of hormonal contraception
or an intra-uterine device. Use of abstinence alone is not considered adequate. Use of
a barrier method alone is considered adequate only if the male partner was
vasectomized at least six months prior to Screening. Use of a double-barrier method of
contraception is acceptable.
Exclusion Criteria:
1. Diagnosed with RA prior to 16 years of age;
2. Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at
Screening;
3. History within one year prior to randomization of illicit drug use;
4. History of alcohol abuse at any time in the past;
5. Use of infliximab, adalimumab, abatacept, certolizumab, golimumab, or tocilizumab
within 8 weeks of randomization;
6. Use of leflunomide within 6 months of randomization;
7. Use of etanercept or anakinra within 4 weeks of randomization;
8. Use of rituximab or ocrelizumab, or cytotoxic agents, such as cyclophosphamide or
chlorambucil, within one year of randomization;
9. Currently taking cytochrome P450 inhibitors including protease inhibitors such as
ritonavir,indinavir, nelfinavir, or macrolide antibiotics such as erythromycin,
telithromycin,clarithromycin, or azole antifungals such as fluconazole, ketoconazole,
itraconazole, or cimetidine, nefazodone, bergamottin (constituent of grapefruit
juice), quercetin, aprepitant,or verapamil;
10. History or presence of any form of cancer within the 10 years prior to randomization,
with the exception of excised basal cell or squamous cell carcinoma of the skin, or
cervical carcinoma in situ or breast carcinoma in situ that has been excised or
resected completely and is without evidence of local recurrence or metastasis;
11. Evidence of tuberculosis based on chest X rays, tuberculin skin test, QuantiFERON®-TB
Gold test, or T-SPOT®.TB test performed during screening;
12. Presence of Felty's syndrome, psoriatic arthritis, or other auto-immune diseases;
13. Major surgery (including joint surgery) within 12 weeks prior to randomization;
14. Subject's hemoglobin is less than 11 g/dL (6.83 mmol/L) at Screening;
15. Subject has any evidence of hepatic disease; AST, ALT, alkaline phosphatase, or
bilirubin > 1.5 x the upper limit of normal;
16. Subject has any evidence of renal impairment; serum creatinine > 1.5 x upper limit of
normal;
17. The subject had an infection requiring antibiotic treatment within 4 weeks of
randomization;
18. History or presence of any medical or psychiatric condition or disease, or laboratory
abnormality that, in the opinion of the Investigator, may place the subject at
unacceptable risk for study participation and may prevent the subject from completing
the study; and
19. Participated in any clinical study of an investigational product within 30 days prior
to randomization.
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