ConsideRAte Study - Splenic Stimulation for RA

Official title

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

Overview

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.

Detailed description

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.

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)

Primary outcome measures

• Incidence of Adverse Events [Safety and Tolerability] [Time frame: Up through the end of Period 1 (Period 1 is up to 12 weeks duration)]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: During Period 2 (Period 2 is up to 12 weeks in duration beyond Period 1)]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: During Period 3 (Period 3 is up to 24 weeks in duration beyond Period 2)]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: During Period 4 (Period 4 is up to 5 years in duration beyond Period 3)]

Secondary outcome measures (12)

• Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP) [Time frame: Baseline to 12 weeks (Period 1)]
• Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFα) in whole blood assay [Time frame: Baseline to 12 weeks (Period 1)]
• Change in the level of LPS-inducible release of TNFα in whole blood assay [Time frame: Baseline to 24 weeks (Period 2)]
• Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay [Time frame: Baseline to 12 weeks (Period 1)]
• Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay [Time frame: Baseline to 24 weeks (Period 2)]
• Change in the level of LPS-inducible release of IL-8 in whole blood assay [Time frame: Baseline to 12 weeks (Period 1)]
• Change in the level of LPS-inducible release of IL-8 in whole blood assay [Time frame: Baseline to 24 weeks (Period 2)]
• Change in the level of LPS-inducible release of IL-17 in whole blood assay [Time frame: Baseline to 12 weeks (Period 1)]
• Change in the level of LPS-inducible release of IL-17 in whole blood assay [Time frame: Baseline to 24 weeks (Period 2)]
• Change in DAS28-CRP [Time frame: Baseline to 24 weeks (Period 2)]
• Change in DAS28-CRP [Time frame: Baseline to 36 weeks (Period 3)]
• Change in DAS28-CRP [Time frame: Baseline to 48 weeks (Period 3)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 12 centers

• Pinnacle Research Group, LLC — Anniston
• Medvin Research - Covina — Covina
• Medvin Research - Whittier — Whittier
• The Osteoporosis & Clinical Trials Center — Hagerstown
• NYU Langone — Brooklyn
• Oregon Health & Science University — Portland
• Altoona Center for Clinical Research — Altoona
• Arthritis & Rheumatology Institute — Allen
• … and 4 more centers

Netherlands · 2 centers

• Academic Medical Center (AMC) Dept of Rheumatology & Clinical Immunology — Amsterdam
• Maxima Medical Center, MMC — Eindhoven

Identifiers

NCT: NCT05003310 · GAL1040

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗