Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19 and CYP3A4

Inclusion Criteria

• Subjects willing and able to give voluntary informed consent and sign an Informed Consent Form (ICF)
• Male subjects and their female partners and female subjects of childbearing potential must agree to adhere to the contraceptive requirements for the study

Female subjects of non-childbearing potential must be:

• Surgically sterile (i.e. bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 months prior to first dosing), or
• Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to first dosing, with a follicle stimulating hormone level at screening of ≥40 mIU/mL.
• Body mass index of 18 kg/m2 to 29.9 kg/m2, inclusive, and body weight of 55 kg to 110 kg, inclusive, if male, and 45 kg to 100 kg, inclusive, if female.
• Subjects must have a diagnosis of adult onset RA classified by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 revised classification criteria for RA (Aletaha et al, 2010) for at least 12 weeks prior to Screening. If the subject was previously diagnosed according to ACR 1987 criteria, the Investigator may classify the subject per ACR 2010 retrospectively, based on medical history, and using available source data.
• Subjects must have received Methotrexate (MTX), sulfasalazine, or hydroxychloroquine for at least 12 weeks prior to Day 1 and in stable dose for at least 6 weeks prior to Day 1 without significant Adverse events (AEs). Stable doses of MTX should be 10 mg to 25 mg weekly with folic acid (at least 5 mg weekly or equivalent). No significant side effects based on the Investigator's judgment should be observed during treatment by these agents. The maximum allowed doses of sulfasalazine and hydroxychloroquine are:
• Sulfasalazine: 3 g per day
• Hydroxychloroquine: 400 mg per day

Note: The doses should remain stable and not be changed from the time of signing the ICF until the end of the treatment period (EOT, Day 29).

• Subjects must have an increased CRP at Screening (of ≥1.2 × ULN).
• Female subjects of childbearing potential must have negative pregnancy test at Screening and throughout the study until the end of study (EOS) (Day 161).

Exclusion Criteria

• Diagnosis of any other inflammatory arthritis or systemic inflammatory disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). Osteoarthritis is classified as a degenerative disease rather than an inflammatory disease.
• Subjects with Steinbrocker Class III or IV functional capacity (incapacitated, largely, or wholly bed ridden, or confined to a wheelchair, with little, or no self-care).
• Prior exposure to any licensed or investigational compound directly or indirectly targeting IL-6 or IL-6R within 12 months of Day 1.
• Treatment with DMARDs other than MTX, hydroxychloroquine, or sulfasalazine. Treatment with the following DMARDs are not allowed within the specified time period prior to Day 1:
• 4 weeks for azathioprine, cyclosporine, chloroquine, gold, penicillamine, minocycline, or doxycycline.
• 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to Day 1: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours or activated charcoal at a dosage of 50 grams 4 times a day for at least 24 hours.
• 24 weeks for cyclophosphamide.
• Treatment with any cell-depleting therapies including anti-cluster of differentiation (CD)20 or investigational agents (eg, CAMPATH®, anti-CD4, anti-CD5, anti-CD3, and anti-CD19) with the exception of rituximab. Treatment with rituximab is not allowed within 6 months of Day 1.
• Treatment with Tumor necrosis factor alpha inhibitor (TNFi) (including investigational proposed or licensed biosimilars) or any other biologic therapy for the treatment of RA within 12 weeks of Day 1.
• Use of parenteral