ConsideRAte Study - Splenic Stimulation for RA

Multipart Exploratory Study to Evaluate Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis

This study will evaluate the safety, tolerability, and effects of stimulating the splenic neurovascular bundle (NVB) with the Galvani System, which consists of a lead, implantable pulse generator, external components and accessories. The study will consist of 4 study periods, including a Randomized Control Trial period (Period 1), an Open Label period (Period 2), a Treat-to-target period (Period 3), and a Long-term Follow-up period (Period 4). Participants eligible for implant will have active rheumatoid arthritis (RA) and have an inadequate response or intolerance to at least two biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) or JAK inhibitors (JAKis). A sufficient number of participants will be enrolled so that approximately 28 participants will undergo device implantation.

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.

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