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

• ClinicalTrials.gov Identifier: NCT03437473
• Recruitment Status: Completed
• First Posted: February 19, 2018
• Last Update Posted: December 27, 2018
• Sponsor: SetPoint Medical Corporation
• Information provided by (Responsible Party): SetPoint Medical Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Device Feasibility
• Official Title: A Randomized Controlled Study of the Safety and Efficacy of Neurostimulation Using a Vagus Nerve Stimulation Device in Patients With Rheumatoid Arthritis
• Actual Study Start Date: March 6, 2018
• Actual Primary Completion Date: December 10, 2018
• Actual Study Completion Date: December 10, 2018

Arms and Interventions

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 Name: 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 Name: SetPoint System
Sham Comparator: No stimulation	Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System; Active Implantable Vagus Nerve Stimulation device.; Other Name: SetPoint System

Outcome Measures

Primary Outcome Measures :

1. incidence of Adverse Events [ Time Frame: Enrollment to Week 12 ]
   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

Secondary Outcome Measures :

1. change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP) [ Time Frame: change from baseline at Day 0 and Week 12 ]
   comparison between the active device group and the inactive device group of the change in DAS28-CRP
2. change in American College of Rheumatology (ACR) 20, 50 and 70 response rates [ Time Frame: change from baseline at Day 0 and Week 12 ]
   comparison between the active device group and the inactive device group of the change in ACR 20/50/70
3. change in European League Against Rheumatism (EULAR) response and remission rate [ Time Frame: change from baseline at Day 0 and Week 12 ]
   comparison between the active device group and the inactive device group of the change in EULAR
4. change in hand MRI [ Time Frame: change from baseline at Day 0 and Week 12 ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Florida

Arthritis & Rheumatic Disease Specialties

Aventura, Florida, United States, 33180

Florida Medical Clinic, P.A.

Zephyrhills, Florida, United States, 33542

United States, New York

Northwell Health Division of Rheumatology

Great Neck, New York, United States, 11021

United States, Pennsylvania

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States, 16635

Sponsors and Collaborators

SetPoint Medical Corporation

Investigators

• Study Director: Mark Genovese, MD; Stanford University

More Information

• Responsible Party: SetPoint Medical Corporation
• ClinicalTrials.gov Identifier: NCT03437473
• Other Study ID Numbers: SPM-008
• First Posted: February 19, 2018
• Last Update Posted: December 27, 2018
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Anti-Inflammatory Agents; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs