ConsideRAte Study - Splenic Stimulation for RA

Galvani Bioelectronics28 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Interventions

Active StimulationDEVICE

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

Sham StimulationDEVICE

Sham stimulation will be provided during the period

BaricitinibDRUG

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

Background TreatmentDRUG

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

Eligibility

Sex: ALLMin age: 22 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (14)

Pinnacle Research Group, LLC

Anniston, Alabama, United States

WITHDRAWN

Medvin Research - Covina

Covina, California, United States

RECRUITING

Medvin Research - Whittier

Whittier, California, United States

RECRUITING

The Osteoporosis & Clinical Trials Center

Hagerstown, Maryland, United States

RECRUITING

NYU Langone

Brooklyn, New York, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

RECRUITING

Altoona Center for Clinical Research

Altoona, Pennsylvania, United States

RECRUITING

Arthritis & Rheumatology Institute

Allen, Texas, United States

RECRUITING

St. David's Healthcare

Austin, Texas, United States

RECRUITING

Tekton Research

Austin, Texas, United States

RECRUITING

...and 4 more locations

Outcomes

Primary Outcomes

Incidence of Adverse Events [Safety and Tolerability]

Adverse Events (AEs) may include clinically significant findings from Laboratory Safety Assessments (clinical chemistry and hematology), vital signs (blood pressure, heart rate, respiratory rate, and body temperature), and 12-Lead EKG

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 Outcomes

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)

Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score

Time frame: Baseline to 12 weeks (Period 1)

Change in HAQ-DI score

Time frame: Baseline to 24 weeks (Period 2)

Change in HAQ-DI score

Time frame: Baseline to 36 weeks (Period 3)

Change in HAQ-DI score

Time frame: Baseline to 48 weeks (Period 3)

Change in Short Form 36 (SF-36) physical component score

Time frame: Baseline to 12 weeks (Period 1)

Change in SF-36 physical component score

Time frame: Baseline to 24 weeks (Period 2)

Change in SF-36 physical component score

Time frame: Baseline to 36 weeks (Period 3)

Change in SF-36 physical component score

Time frame: Baseline to 48 weeks (Period 3)

Change in SF-36 mental component score

Time frame: Baseline to 12 weeks (Period 1)

Change in SF-36 mental component score

Time frame: Baseline to 24 weeks (Period 2)

Change in SF-36 mental component score

Time frame: Baseline to 36 weeks (Period 3)

Change in SF-36 mental component score

Time frame: Baseline to 48 weeks (Period 3)

Change in SF-36 domain score

Time frame: Baseline to 12 weeks (Period 1)

Change in SF-36 domain score

Time frame: Baseline to 24 weeks (Period 2)

Change in SF-36 domain score

Time frame: Baseline to 36 weeks (Period 3)

Change in SF-36 domain score

Time frame: Baseline to 48 weeks (Period 3)

To evaluate the usability of the external Galvani System devices and accessories

Summarize feedback collected on a questionnaire pertaining to the use of the external Galvani System devices

Time frame: Through 48 weeks

To evaluate the participants' perception of therapy and sensation

A form is provided to participants at each visit after randomization to describe any sensations that may be associated with the Galvani System

Time frame: Through 48 weeks

Evaluate device performance as assessed by tabulation of device deficiencies

Time frame: Through 48 weeks

Change in DAS28-CRP in participants who remain on active stimulation during Period 2

Time frame: week 12 to week 24

Incidence of participants who remain on active stimulation achieving DAS28-CRP score <2.6 at the end of Period 2

Time frame: Time Frame: Week 24

Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2

Time frame: week 12 to week 24

Incidence of a change in DAS28-CRP greater than 1.2 units in participants who are given Drug treatment with baricitinib during Period 2

Time frame: week 12 to week 24

Incidence of participants who are given drug treatment with baricitinib achieving DAS28-CRP score <2.6 at the end of Period 2

Time frame: Week 24

ConsideRAte Study - Splenic Stimulation for RA

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts