Safety and Efficacy of Vagus Nerve Stimulator in Patients With Rheumatoid Arthritis (RA)

A Randomized Controlled Study of the Safety and Efficacy of Neurostimulation Using a Vagus Nerve Stimulation Device in Patients With Rheumatoid Arthritis

Multi-site, first-in-human study to assess safety and efficacy of an active implantable Vagus Nerve Stimulation (VNS) device in 15 adult patients with active moderate-to-severe rheumatoid arthritis who have had an incomplete response or intolerability to at least two different mechanisms of action.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System

Detailed Description

This is a two-stage study where Stage 1 is open label, and Stage 2 is randomized and sham controlled where the sites and subjects are blinded to treatment. Three subjects will be enrolled in Stage 1 of the study. And 12 subjects will be enrolled in Stage 2. Subjects will be treated for a total of 12 weeks.

Subjects will be asked to visit the clinic at day 0, week 1-6, week 8 and week 12. During these visits, the following activities will be conducted: standard patient and physician assessments of RA activity, blood sample collection for RA biomarkers, and a hand MRI.

Subjects who complete the study will have the option to enroll in a long-term extension study. Subjects that do not participate in the extension study can opt to either have their device permanently inactivated and left in place or have the device surgically explanted.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis & Rheumatic Disease Specialties
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic, P.A.
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health Division of Rheumatology
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female and 22-75 years of age, inclusive
2. Have provided informed consent
3. Have a diagnosis of adult-onset rheumatoid arthritis as defined by the 2010 ACR/EULAR classification criteria (Aletaha, 2010)
4. Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints and CDAI score >10

5. Have been treated at approved doses with at least 2 biologic DMARDs and/or new targeted synthetic DMARDs (e.g. JAK inhibition) for at least 3 months and either:

   1. experienced insufficient efficacy or loss of efficacy
   2. experienced intolerance of such treatment
6. Have had regular use of at least 1 conventional DMARDs for at least the 12 weeks prior to study entry with a continuous, non-changing dose for at least 8 weeks prior to screening visit
7. Women of childbearing potential must not be pregnant at the time of screening and must agree to use a double barrier method of contraception throughout the study

Exclusion Criteria:

1. Have taken the following within the defined time period prior to screening visit:

   i. Rituximab: 6 months ii. Infliximab, golimumab, adalimumab, certolizumab pegol, tocilizumab: 60 days iii. Abatacept, etanercept, anakinra: 30 days iv. Tofacitinib: 30 days v. Investigational biologic agents: 6 months for depleting agents, 60 days for others vi. Investigational small molecules: 5 times the pharmacokinetic half-life or 30 days, whichever is longer vii. Intra-articular corticosteroid injection: 30 days

2. Are currently receiving corticosteroids at doses greater than 10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of screening visit
3. Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of screening visit
4. Documented significant psychiatric illness or substance abuse
5. Active infection requiring treatment with antibiotics
6. Uncontrolled hypertension
7. Uncontrolled diabetes
8. History of stroke
9. Known cardiac disease, including cardiomyopathy with ejection fraction <40%, recent myocardial infarction or unstable angina, or heart failure with New York Heart Association class III or IV symptoms
10. Known neurological syndromes
11. Known atherosclerotic disease including contralateral carotid artery
12. BMI <18.5 or >35
13. Any condition per the investigator's clinical judgment that precludes participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active stimulation QD	Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System; Active Implantable Vagus Nerve Stimulation device.; Other Names: SetPoint System
Active Comparator: Active stimulation QID	Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System; Active Implantable Vagus Nerve Stimulation device.; Other Names: SetPoint System
Sham Comparator: No stimulation	Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System; Active Implantable Vagus Nerve Stimulation device.; Other Names: SetPoint System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of Adverse Events	treatment-emergent incidence rates of Adverse Events, Adverse Device Effects, Serious Adverse Events, Serious Adverse Device Effects, Unanticipated Adverse Device Effects, and Unanticipated Serious Adverse Device Effects	Enrollment to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP)	comparison between the active device group and the inactive device group of the change in DAS28-CRP	change from baseline at Day 0 and Week 12
change in American College of Rheumatology (ACR) 20, 50 and 70 response rates	comparison between the active device group and the inactive device group of the change in ACR 20/50/70	change from baseline at Day 0 and Week 12
change in European League Against Rheumatism (EULAR) response and remission rate	comparison between the active device group and the inactive device group of the change in EULAR	change from baseline at Day 0 and Week 12
change in hand MRI	comparison between the active device group and the inactive device group of the change in Outcomes Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS) hand MRI index of synovitis	change from baseline at Day 0 and Week 12

Collaborators and Investigators

• Sponsor: SetPoint Medical Corporation
• Investigators: Study Director: Mark Genovese, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2018
• Primary Completion (Actual): December 10, 2018
• Study Completion (Actual): December 10, 2018

Study Registration Dates

• First Submitted: February 6, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 27, 2018
• Last Update Submitted That Met QC Criteria: December 26, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Cholinergic Agents
• Other Study ID Numbers: SPM-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes