Splenic Stimulation for RA

Sponsor

Galvani Bioelectronics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05003310

Collaborator

NAMSA (Other), Q2 Solutions (Industry)

Enrollment

Locations

Arms

86.4

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Device: Active Stimulation Device: Sham Stimulation Drug: Baricitinib Drug: Background Treatment	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

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 periodMulticenter 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

Official Title:

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

Actual Study Start Date :

Oct 19, 2021

Anticipated Primary Completion Date :

Jan 1, 2029

Anticipated Study Completion Date :

Jan 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Stimulation; Period 1 Active stimulation for 12 weeks in addition to stable dose of csDMARD therapy.	Device: Active Stimulation Stimulation will be turned ON and applied during each day of the period. Drug: Background Treatment Stable dose of standard background treatment (e.g., csDMARD therapy)
Sham Comparator: Sham Stimulation; Period 1 Sham stimulation for 12 weeks in addition to stable dose of csDMARD therapy.	Device: Sham Stimulation Sham stimulation will be provided during the period Drug: Background Treatment Stable dose of standard background treatment (e.g., csDMARD therapy)
Experimental: Open label active stimulation, Period 2 Open label active stimulation for 12 additional weeks in addition to stable dose of csDMARD therapy.	Device: Active Stimulation Stimulation will be turned ON and applied during each day of the period. Drug: Background Treatment Stable dose of standard background treatment (e.g., csDMARD therapy)
Other: Open label RA Drug, Period 2 Open label drug treatment with baricitinib for 12 weeks in addition to stable dose of csDMARD therapy.	Drug: Baricitinib Baricitinib (2 mg) is administered daily during the period. Drug: Background Treatment Stable dose of standard background treatment (e.g., csDMARD therapy)
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.	Device: Active Stimulation Stimulation will be turned ON and applied during each day of 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)
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.	Device: Active Stimulation Stimulation will be turned ON and applied during each day of 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)
Other: Long-term Follow-up, Period 4 Standard of care treatments with or without stimulation	Device: Active Stimulation Stimulation will be turned ON and applied during each day of the period. Drug: Background Treatment Stable dose of standard background treatment (e.g., csDMARD therapy)

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Events [Safety and Tolerability] [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] [During Period 2 (Period 2 is up to 12 weeks in duration beyond Period 1)]
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [During Period 3 (Period 3 is up to 24 weeks in duration beyond Period 2)]
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [During Period 4 (Period 4 is up to 5 years in duration beyond Period 3)]

Secondary Outcome Measures

Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP) [Baseline to 12 weeks (Period 1)]
Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFα) in whole blood assay [Baseline to 12 weeks (Period 1)]
Change in the level of LPS-inducible release of TNFα in whole blood assay [Baseline to 24 weeks (Period 2)]
Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay [Baseline to 12 weeks (Period 1)]
Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay [Baseline to 24 weeks (Period 2)]
Change in the level of LPS-inducible release of IL-8 in whole blood assay [Baseline to 12 weeks (Period 1)]
Change in the level of LPS-inducible release of IL-8 in whole blood assay [Baseline to 24 weeks (Period 2)]
Change in the level of LPS-inducible release of IL-17 in whole blood assay [Baseline to 12 weeks (Period 1)]
Change in the level of LPS-inducible release of IL-17 in whole blood assay [Baseline to 24 weeks (Period 2)]
Change in DAS28-CRP [Baseline to 24 weeks (Period 2)]
Change in DAS28-CRP [Baseline to 36 weeks (Period 3)]
Change in DAS28-CRP [Baseline to 48 weeks (Period 3)]
Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score [Baseline to 12 weeks (Period 1)]
Change in HAQ-DI score [Baseline to 24 weeks (Period 2)]
Change in HAQ-DI score [Baseline to 36 weeks (Period 3)]
Change in HAQ-DI score [Baseline to 48 weeks (Period 3)]
Change in Short Form 36 (SF-36) physical component score [Baseline to 12 weeks (Period 1)]
Change in SF-36 physical component score [Baseline to 24 weeks (Period 2)]
Change in SF-36 physical component score [Baseline to 36 weeks (Period 3)]
Change in SF-36 physical component score [Baseline to 48 weeks (Period 3)]
Change in SF-36 mental component score [Baseline to 12 weeks (Period 1)]
Change in SF-36 mental component score [Baseline to 24 weeks (Period 2)]
Change in SF-36 mental component score [Baseline to 36 weeks (Period 3)]
Change in SF-36 mental component score [Baseline to 48 weeks (Period 3)]
Change in SF-36 domain score [Baseline to 12 weeks (Period 1)]
Change in SF-36 domain score [Baseline to 24 weeks (Period 2)]
Change in SF-36 domain score [Baseline to 36 weeks (Period 3)]
Change in SF-36 domain score [Baseline to 48 weeks (Period 3)]
To evaluate the usability of the external Galvani System devices and accessories [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 [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 [Through 48 weeks]
Change in DAS28-CRP in participants who remain on active stimulation during Period 2 [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: Week 24]
Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2 [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 [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 [Week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group, LLC	Anniston	Alabama	United States	36207
2	NYU Langone	Brooklyn	New York	United States	11201
3	St. David's Healthcare	Austin	Texas	United States	78705
4	Metroplex Clinical Research Center	Dallas	Texas	United States	75231