Splenic Stimulation for RA

• ClinicalTrials.gov Identifier: NCT05003310
• Recruitment Status: Recruiting
• First Posted: August 12, 2021
• Last Update Posted: February 14, 2024
• Sponsor: Galvani Bioelectronics
• Collaborators: NAMSA; Q2 Solutions
• Information provided by (Responsible Party): Galvani Bioelectronics

Tracking Information

• First Submitted Date: July 5, 2021
• First Posted Date: August 12, 2021
• Last Update Posted Date: February 14, 2024
• Actual Study Start Date: October 19, 2021
• Estimated Primary Completion Date: January 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 5, 2021)

• Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: Up through the end of Period 1 (Period 1 is up to 12 weeks duration) ]
  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
• 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) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 5, 2021)

• 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 [ Time Frame: Through 48 weeks ]
  Summarize feedback collected on a questionnaire pertaining to the use of the external Galvani System devices
• To evaluate the participants' perception of therapy and sensation [ Time Frame: Through 48 weeks ]
  A form is provided to participants at each visit after randomization to describe any sensations that may be associated with the Galvani System
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Splenic Stimulation for RA
• Official Title: Multipart Exploratory Study to Evaluate Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis
• Brief Summary: 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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Multicenter study with 4 periods. Period 1 is a randomized, controlled double-blind period where participants are assigned randomly to either active or sham stimulation. During the open-label Periods 2 through 4, participants are assigned treatment based on responses to treatments in the prior period

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Rheumatoid Arthritis

Intervention

• 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)

Study Arms

• Experimental: Active Stimulation; Period 1
  Active stimulation for 12 weeks in addition to stable dose of csDMARD therapy.
  Interventions:

  • Device: Active Stimulation
  • Drug: Background Treatment
• Sham Comparator: Sham Stimulation; Period 1
  Sham stimulation for 12 weeks in addition to stable dose of csDMARD therapy.
  Interventions:

  • Device: Sham Stimulation
  • Drug: Background Treatment
• Experimental: Open label active stimulation, Period 2
  Open label active stimulation for 12 additional weeks in addition to stable dose of csDMARD therapy.
  Interventions:

  • Device: Active Stimulation
  • Drug: Background Treatment
• Open label RA Drug, Period 2
  Open label drug treatment with baricitinib for 12 weeks in addition to stable dose of csDMARD therapy.
  Interventions:

  • Drug: Baricitinib
  • Drug: Background Treatment
• Experimental: RA drug combined with active stimulation, Period 3
  Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.
  Interventions:

  • Device: Active Stimulation
  • Drug: Baricitinib
  • Drug: Background Treatment
• Experimental: Active stimulation combined with RA drug, Period 3
  Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.
  Interventions:

  • Device: Active Stimulation
  • Drug: Baricitinib
  • Drug: Background Treatment
• Long-term Follow-up, Period 4
  Standard of care treatments with or without stimulation
  Interventions:

  • Device: Active Stimulation
  • Drug: Background Treatment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 5, 2021): 28
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2029
• Estimated Primary Completion Date: January 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult-onset RA of at least six months duration
• 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 treatment with standard dose(s) of conventional synthetic DMARD(s)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 22 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Operations Director; +1 877 613 9001; clinical@galvani.bio

• Listed Location Countries: Netherlands, United States

Administrative Information

• NCT Number: NCT05003310
• Other Study ID Numbers: GAL1040
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Galvani Bioelectronics
• Original Responsible Party: Same as current
• Current Study Sponsor: Galvani Bioelectronics
• Original Study Sponsor: Same as current

Collaborators

• NAMSA
• Q2 Solutions

• Investigators: Not Provided
• PRS Account: Galvani Bioelectronics
• Verification Date: February 2024