ConsideRAte Study - Splenic Stimulation for RA

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05003310
• Other study ID #: GAL1040
• Status: Recruiting
• Phase: N/A
• Start date: October 19, 2021
• Est. completion date: April 2032

Study information

• Verified date: May 2024
• Source: Galvani Bioelectronics
• Contact: Operations Director
• Phone: +1 877 613 9001
• Email: clinical[@]galvani.bio
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: April 2032
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Device:
• Active Stimulation
Stimulation will be turned ON and applied during each day of the period.
• Sham Stimulation
Sham stimulation will be provided during the period

Drug:
• Baricitinib
Baricitinib (2 mg) is administered daily during the period.
• Background Treatment
Stable dose of standard background treatment (e.g., csDMARD therapy)

Locations

Country	Name	City	State
Netherlands	Academic Medical Center (AMC) Dept of Rheumatology & Clinical Immunology	Amsterdam
Netherlands	Maxima Medical Center, MMC	Eindhoven
United States	Arthritis & Rheumatology Institute	Allen	Texas
United States	Altoona Center for Clinical Research	Altoona	Pennsylvania
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	St. David's Healthcare	Austin	Texas
United States	Tekton Research	Austin	Texas
United States	NYU Langone	Brooklyn	New York
United States	Medvin Research - Covina	Covina	California
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	The Osteoporosis & Clinical Trials Center	Hagerstown	Maryland
United States	Southwest Rheumatology Research	Mesquite	Texas
United States	Oregon Health & Science University	Portland	Oregon
United States	Medvin Research - Whittier	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
Galvani Bioelectronics	NAMSA, Q2 Solutions

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up through the end of Period 1 (Period 1 is up to 12 weeks duration)
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		During Period 2 (Period 2 is up to 12 weeks in duration beyond Period 1)
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		During Period 3 (Period 3 is up to 24 weeks in duration beyond Period 2)
Primary	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	Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP)		Baseline to 12 weeks (Period 1)
Secondary	Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFa) in whole blood assay		Baseline to 12 weeks (Period 1)
Secondary	Change in the level of LPS-inducible release of TNFa in whole blood assay		Baseline to 24 weeks (Period 2)
Secondary	Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay		Baseline to 12 weeks (Period 1)
Secondary	Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay		Baseline to 24 weeks (Period 2)
Secondary	Change in the level of LPS-inducible release of IL-8 in whole blood assay		Baseline to 12 weeks (Period 1)
Secondary	Change in the level of LPS-inducible release of IL-8 in whole blood assay		Baseline to 24 weeks (Period 2)
Secondary	Change in the level of LPS-inducible release of IL-17 in whole blood assay		Baseline to 12 weeks (Period 1)
Secondary	Change in the level of LPS-inducible release of IL-17 in whole blood assay		Baseline to 24 weeks (Period 2)
Secondary	Change in DAS28-CRP		Baseline to 24 weeks (Period 2)
Secondary	Change in DAS28-CRP		Baseline to 36 weeks (Period 3)
Secondary	Change in DAS28-CRP		Baseline to 48 weeks (Period 3)
Secondary	Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score		Baseline to 12 weeks (Period 1)
Secondary	Change in HAQ-DI score		Baseline to 24 weeks (Period 2)
Secondary	Change in HAQ-DI score		Baseline to 36 weeks (Period 3)
Secondary	Change in HAQ-DI score		Baseline to 48 weeks (Period 3)
Secondary	Change in Short Form 36 (SF-36) physical component score		Baseline to 12 weeks (Period 1)
Secondary	Change in SF-36 physical component score		Baseline to 24 weeks (Period 2)
Secondary	Change in SF-36 physical component score		Baseline to 36 weeks (Period 3)
Secondary	Change in SF-36 physical component score		Baseline to 48 weeks (Period 3)
Secondary	Change in SF-36 mental component score		Baseline to 12 weeks (Period 1)
Secondary	Change in SF-36 mental component score		Baseline to 24 weeks (Period 2)
Secondary	Change in SF-36 mental component score		Baseline to 36 weeks (Period 3)
Secondary	Change in SF-36 mental component score		Baseline to 48 weeks (Period 3)
Secondary	Change in SF-36 domain score		Baseline to 12 weeks (Period 1)
Secondary	Change in SF-36 domain score		Baseline to 24 weeks (Period 2)
Secondary	Change in SF-36 domain score		Baseline to 36 weeks (Period 3)
Secondary	Change in SF-36 domain score		Baseline to 48 weeks (Period 3)
Secondary	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	Through 48 weeks
Secondary	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	Through 48 weeks
Secondary	Evaluate device performance as assessed by tabulation of device deficiencies		Through 48 weeks
Secondary	Change in DAS28-CRP in participants who remain on active stimulation during Period 2		week 12 to week 24
Secondary	Incidence of participants who remain on active stimulation achieving DAS28-CRP score <2.6 at the end of Period 2		Time Frame: Week 24
Secondary	Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2		week 12 to week 24
Secondary	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
Secondary	Incidence of participants who are given drug treatment with baricitinib achieving DAS28-CRP score <2.6 at the end of Period 2		Week 24