Study to Assess the Safety and Efficacy of Enbrel Administered by Sofusa DoseConnect for Rheumatoid Arthritis

Inclusion Criteria:

• Provides written informed consent
• Has rheumatoid arthritis (RA) as defined by having a score of 6 or higher on the 2010 ACR-EULAR classification criteria
• Is currently on Enbrel therapy and has received once-weekly Enbrel injections for at least 12 weeks with no more than 1 missed dose in the 12 weeks prior to Screening.
• Must meet the following disease criteria:

Have a DAS28(CRP) score > 2.9 at Screening Have a DAS28(ESR) score > 3.2 at Screening Swollen joint count ≥ 3 (28-joint count) and Tender joint count ≥ 3 (28-joint count) at Screening and Baseline

• If on oral or subcutaneous MTX (up to 25 mg/week) or other permitted oral conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) (i.e., leflunomide, up to 20 mg/day; hydroxychloroquine, up to 400 mg/day; or sulfasalazine, up to 3 g/day), must be on stable dose (MTX ≥ 12 weeks and other permitted DMARDs ≥ 8 weeks) within the specified ranges prior to Baseline. Note: if on methotrexate (MTX), subjects must be on a stable dose of folic acid (total ≥ 5 mg per week for ≥ 12 weeks) prior to Baseline and must continue a stable dose during the course of the study.
• If taking regular nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, paracetamol/acetaminophen, or oral glucocorticoids for treatment of RA symptoms, must be on stable dose and route of administration for at least 2 weeks before Baseline
• Females of childbearing potential must agree to use acceptable method(s) of contraception for the duration of the study and for 3 months after the last dose of study drug

Exclusion Criteria:

• Has participated in a clinical trial with a drug or device within 30 days prior to Screening
• Prior treatment with investigational therapy within 30 days or 5 half-lives before Screening (whichever is longer)
• History of hypersensitivity to any recombinant protein drugs or any of the excipients used in Enbrel
• Has skin contact sensitivities (due to SOFUSA device adhesive) or allergies to iodine (due to the iodine in ICG)
• Lack of any clinical response to Enbrel in the Investigator's opinion
• Treatment with other biologic agents (e.g., interleukin [IL] 6, IL17, IL12/23 inhibitors; abatacept, tumor necrosis factor [TNF] inhibitors) besides Enbrel within 24 weeks before Baseline
• Previous treatment with more than 2 other tumor necrosis factor (TNF) inhibitor therapies (besides Enbrel), more than 2 targeted therapies with different mechanisms of action (e.g., Janus kinase inhibitors, T cell costimulation inhibitor, IL-6 receptor antagonist), or any cell depleting agents (e.g., anti-CD20)
• Use of chlorambucil or cyclophosphamide within 24 weeks of Baseline
• Use of leflunomide within 8 weeks of Baseline, if washing out of leflunomide, unless a cholestyramine washout has been performed, then use of leflunomide within 4 weeks of Baseline
• Use of MTX, hydroxychloroquine, or sulfasalazine within 4 weeks of Baseline, if washing out of MTX, hydroxychloroquine, or sulfasalazine
• Any systemic nonbiologic DMARD (e.g., Janus kinase inhibitor, cyclosporine, azathioprine) within 4 weeks of Baseline
• History of or ongoing inflammatory, autoimmune, or painful musculoskeletal diseases (except for Sjogren's syndrome or fibromyalgia) which could interfere with the RA assessments as determined by the Investigator
• Functional RA status of class IV according to the ACR 1991 revised criteria at Screening or Baseline
• Oral glucocorticoids > 10 mg/day prednisone equivalent within 4 weeks prior to Baseline
• Opioid tolerant: defined as the use of opiate analgesics at a dose of > 30 mg/day of oral morphine equivalent on 4 of the last 7 days prior to Baseline
• Use of intramuscular, intravenous, or intraarticular corticosteroid therapy within 4 weeks prior to Baseline
• Treatment with any intra-articular hyaluronic acid preparation within 12 weeks prior to Baseline
• Chronic arthritis diagnosis before the age of 17 years
• Presence of any extra-articular manifestations of RA, except for rheumatoid nodules
• Joint surgery within the preceding 8 weeks before Screening
• History of, or presence of cancer (if < 5 years from successful treatment even with no evidence of recurrent disease) or lymphoproliferative or hematologic disease, other than a successfully and completely treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or removed non-invasive colon or bladder polyps, with no evidence of recurrence
• History of uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (New York Heart Association III-IV), active peptic ulcer disease, recent stroke, myocardial infarction, or thromboembolism (within 6 months), or any other condition which, in the opinion of the Investigator, would put the patient at risk by participation in the study
• Previous diagnosis or signs of demyelinating disease
• History of clinically significant hematologic (e.g. severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g. glomerulonephritis, fibrosis, cirrhosis, hepatitis) or abnormal clinical laboratory tests at Screening
• Receipt of any blood products within 12 weeks of Baseline
• History of persistent chronic infection; recurrent infection (more than 3 infections requiring antimicrobial therapy within the last 12 months); or active infections requiring hospitalization or treatment with systemic anti-infective therapy within 4 weeks before Screening (counted from anti-infective therapy stop date), except for fungal infection of nails or nail beds
• History of or current active tuberculosis or presence of latent tuberculosis as detected by imaging (e.g., chest radiograph) and/ or QuantiFERON®-TB Gold Plus test (QFT) NOTE: Positive QFT (or 2 or more tests that are indeterminate) and/or positive imaging result (within 12 weeks prior to Screening or at Screening) excludes a patient from participation in the study (except for patients who have documentation of completing an acceptable regimen for treatment of latent tuberculosis with no known re-exposure to tuberculosis since treatment completion)
• History or evidence of opportunistic infections (eg, histoplasmosis, listeriosis, legionellosis)
• Known immune deficiency, known human immunodeficiency virus (HIV) positive or positive at Screening, or immunocompromised for other reasons
• Serology positive for hepatitis B virus (HBV) surface antigen (HBsAg) or core antibody (HBcAb) or hepatitis C virus (HCV) antibody (HCV-Ab) or ribonucleic acid (HCV RNA). Patients treated for HCV and considered cured (negative HCV RNA) may participate in the study
• Positive RT-PCR or the equivalent COVID-19 test at Screening
• History or evidence of ongoing significant drug or alcohol abuse
• Known depression or other psychiatric condition, which in the Investigator's opinion may decrease likelihood of participant adherence to the study protocol requirements
• History of vaccination with live vaccines within the preceding 8 weeks prior to Baseline or known to require vaccination with live vaccines during the study period
• For female participants, currently breastfeeding (lactating) or less than 12 weeks from cessation of lactation
• Pregnant woman where pregnancy is defined as the state of a woman after conception and until the termination of gestation, confirmed by a positive serum pregnancy test at Screening or positive urine pregnancy test at Baseline
• Patient is considered by the Investigator, for any reason, to be an unsuitable candidate for the study