Clinical Trial Finder

Inclusion Criteria:

• - RA of at least six months duration, per 2010 ACR/EULAR criteria.

• - Male or female participants, 22-75 years of age.

• - Active RA.

• - Inadequate Response to at least 2 biologic DMARDs and/or JAK-inhibitors (JAKis) including at least one TNF inhibitor.

• - Have an appropriate washout from previously used biological DMARDs or JAKi.

• - Receiving current treatment with standard dose(s) of conventional synthetic DMARD(s) or have documented history of failure due to ineffectiveness or intolerance.

Exclusion Criteria:

• - Inability to provide informed consent.

• - Significant psychiatric disease or substance abuse.

• - History of unilateral or bilateral vagotomy.

• - Active or latent tuberculosis.

• - Known infection with human immunodeficiency virus (HIV); current acute or chronic hepatitis B or hepatitis C; previous hepatitis B.

- Positive SARS COV 2 PCR screening test for COVID-19 infection (at the point of screening for this study) - Currently implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators) - Previous splenectomy

Participants with active rheumatoid arthritis (RA) who receive the implantable system will be randomly assigned to receive either active stimulation or sham-stimulation for 12 weeks (Period 1). Following Period 1, all participants will enter an open label phase (Period 2) during which participants who responded to stimulation will continue on stimulation; whereas participants who received sham stimulation, or were stimulation non-responders, will receive a market-approved RA drug for 12 weeks. At the end of Period 2, participants who respond to their Period 2 therapy but still exhibit signs and symptoms of RA will enter the Treat-to-target period (Period 3); others will proceed to Period 4 (Long-term Follow-up). During the Treat-to-Target period, participants will be treated with dual therapy (stimulation in combination with the market-approved RA drug) for up to 24 weeks. Period 4 provides long term safety follow up for all study participants for a period of 5 years. Participants may receive stimulation in combination with other approved and standard of care therapies, subject to a favorable benefit-risk assessment in the judgement of the treating rheumatologist.

Arms

Experimental: Active Stimulation; Period 1

Active stimulation for 12 weeks

Sham Comparator: Sham Stimulation; Period 1

Sham stimulation for 12 weeks

Experimental: Open label active stimulation, Period 2

Open label active stimulation for 12 additional weeks

Other: Open label RA Drug, Period 2

Open label drug treatment with baricitinib for 12 weeks

Experimental: RA drug combined with active stimulation, Period 3

Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks

Experimental: Active stimulation combined with RA drug, Period 3

Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks

Other: Long-term Follow-up, Period 4

Standard of care treatments with or without stimulation

Interventions

Device: - Active Stimulation

Stimulation will be turned ON and applied during each day of the period.

Device: - Sham Stimulation

Sham stimulation will be provided during the period

Drug: - Baricitinib

Baricitinib (2 mg) is administered daily during the period.

Drug: - Background Treatment

Stable dose of standard background treatment (e.g., csDMARD therapy)