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

Study Overview
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Brief Summary
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Long-term extension of a multi-site, first-in-human study to assess safety and efficacy of an active implantable Vagus Nerve Stimulation (VNS) device in adult patients with active moderate-to-severe rheumatoid arthritis who have had an incomplete response or intolerability to at least two biologic and/or targeted synthetic DMARDs having at least two different mechanisms of action

Detailed Description
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A multicenter, extension study to assess long term safety and efficacy of an active implantable VNS device in adult patients with rheumatoid arthritis. The study is uncontrolled and randomized, where the sites and subjects are blinded to treatment until completion of the parent study. Subjects who were randomized to the inactive device group in the parent study are re-randomized to receive active vagus nerve stimulation either 1 min QD or 1 min QID. Subject who were randomized to the active device groups remain on their assigned treatment (1 min QD, 1 min QID). Study treatment in SPM-011 begins at the Day 0 Visit. At the Day 0, Week 1, 2, 3, 4 and 5 Visits, all subjects are given the opportunity to have the output current of their implant adjusted to the maximum level tolerated. From Week 5 onward, subjects will receive their maximally tolerated output current as 1 min QD or 1 min QID treatment. Follow up assessment visits occur at Week 8, Week 12, Months 6, 9, 12, 18, 24, 30, 33 and 36. Subjects are assessed for safety and durability of response throughout the follow up period. If the subject's symptoms or RA disease worsens, additional concomitant medications are allowed for treatment of their RA.

Official Title
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Long Term Extension Study of the Safety and Efficacy of Neurostimulation Using a Vagus Nerve Stimulation Device in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have enrolled and completed 12 weeks of treatment in Study SPM-008 Women of childbearing potential must not be pregnant and must agree to use a reliable method of contraception throughout the study Exclusion Criteria: Inability to provide consent An adverse event during Study SPM-008 which precludes participation in this study Any condition per the investigator's clinical judgement that precludes participation in the study

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active stimulation QD<br> | Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System<br>* Active Implantable Vagus Nerve Stimulation device.<br>* Other names: SetPoint System;|
| Active Comparator: Active stimulation QID<br> | Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System<br>* Active Implantable Vagus Nerve Stimulation device.<br>* Other names: SetPoint System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rates 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 through Month 36 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP) | Mean change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP) | Day 0 through Month 12 | 
| American College of Rheumatology (ACR) 20, 50 and 70 response rates | Percentage of subjects meeting American College of Rheumatology (ACR) 20, 50 and 70 response status | Day 0 through Month 12 | 
| European League Against Rheumatism (EULAR) response rates | Percentage of subjects meeting European League Against Rheumatism (EULAR) response status of Good, Moderate and None | Day 0 through Month 12 | 
| Disease Activity Score (DAS) 28 - C-reactive protein (CRP) remission rate | Percentage of subjects meeting Disease Activity Score (DAS) 28 - C-reactive protein (CRP) remission | Day 0 through Month 12 |