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Vagus Nerve Stimulation for Moderate to Severe Rheumatoid Arthritis (RESET-RA)

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ClinicalTrials.gov Identifier: NCT04539964
Recruitment Status : Recruiting
First Posted : September 7, 2020
Last Update Posted : July 16, 2021
Sponsor:
Information provided by (Responsible Party):
SetPoint Medical Corporation

Brief Summary:
The RESET-RA study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically placed under general anesthesia on the vagus nerve through a small incision on the left side of the neck (implant procedure). The study will enroll 250 subjects at 40 sites. All eligible subjects will undergo the implant procedure. Half of the subjects will receive active stimulation (treatment) and the other half will receive non-active stimulation (control). After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 180-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Procedure: Implant Procedure Drug: Conventional Synthetic DMARD Device: Active stimulation Device: Non-active stimulation Phase 3

Detailed Description:
The RESET-RA study is an operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter pivotal study enrolling 250 subjects at 40 study centers across the U.S. The study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis (RA) who have had an inadequate response, loss of response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). The implant delivers a small amount of electricity (stimulation) to the nerve. All eligible subjects will undergo the surgery under general anesthesia. Half of the subjects will receive active stimulation (the treatment group) and the other half will receive non-active stimulation (the control group). Stimulation will be delivered for 1 min once per day for 12 weeks. After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 180-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety. Blinding will be maintained until the last enrolled and randomized subject in Stage 2 completes Week 12 assessments, and the study database is locked.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: An operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter study. Subjects will be assigned randomly in a 1:1 ratio into either a treatment or control group. Subjects assigned to the treatment group will receive active stimulation for 1 min once per day, and those assigned to the control group will receive non-active stimulation for 1 min once per day.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: All subjects, investigators, joint evaluators and study staff will be blinded. Blinding of subjects, joint evaluators and investigators will be assessed at Weeks 4 and 12.
Primary Purpose: Treatment
Official Title: Vagus Nerve Stimulation Using the SetPoint System for Moderate to Severe Rheumatoid Arthritis: The RESET-RA Study
Actual Study Start Date : January 11, 2021
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment
Active stimulation for 1 min once per day
Procedure: Implant Procedure
The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.
Other Name: Surgical placement of vagus nerve stimulator inside the neck

Drug: Conventional Synthetic DMARD
All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent
Other Name: Background therapy with conventional synthetic DMARD

Device: Active stimulation
Active stimulation for 1 min once per day

Sham Comparator: Control
Non-active stimulation for 1 min once per day
Procedure: Implant Procedure
The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.
Other Name: Surgical placement of vagus nerve stimulator inside the neck

Drug: Conventional Synthetic DMARD
All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent
Other Name: Background therapy with conventional synthetic DMARD

Device: Non-active stimulation
Non-active stimulation for 1 min once per day




Primary Outcome Measures :
  1. the American College of Rheumatology (ACR) 20 response [ Time Frame: Week 12 ]
    Difference between treatment and control groups in the proportion of subjects who achieve at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worse) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worse), subject pain (0=no pain to 10=worse), evaluator's global assessment (0=best to 10=worse), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL) with higher values representing worse outcome.


Secondary Outcome Measures :
  1. The Disease Activity Score 28-C-reactive protein (DAS28-CRP) good or moderate response as defined by European League Against Rheumatism (EULAR) [ Time Frame: Week 12 ]
    The DAS28-CRP good or moderate response as defined by EULAR based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worse), subject global assessment (0=best to 10=worse) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L) with higher values representing worse outcome

  2. DAS28-CRP response (MCID -1.2) at Week 12 [ Time Frame: Week 12 ]
    DAS28-CRP response based on the minimal clinically important difference (MCID) of -1.2 from baseline

  3. Health Assessment Questionnaire Disability Index (HAQ-DI) response (MCID -0.22) [ Time Frame: Week 12 ]
    HAQ-DI response based on the MCID of -0.22 from baseline

  4. ACR20 response at Week 12 from Day 0 [ Time Frame: Week 12 ]
    Difference between treatment and control groups in the proportion of subjects who achieve at least 20% improvement from Day 0 to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worse) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worse), subject pain (0=no pain to 10=worse), evaluator's global assessment (0=best to 10=worse), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL) with higher values representing worse outcome.



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

Inclusion Criteria:

  • 22-75 years of age at screening
  • Active moderate or severe RA, defined as at least 4/28 tender and 4/28 swollen joints
  • Demonstrated an inadequate response, loss of response, or intolerance to 1 or more approved for rheumatoid arthritis biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including Janus kinase inhibitors (JAKi)
  • Receiving treatment with at least 1 conventional synthetic DMARD for at least 12 weeks and on a continuous non-changing dose and route of administration for at least 4 weeks prior to Screening and able to continue the same stable dose through Week 12

Exclusion Criteria:

  • Untreated or poorly controlled psychiatric illness or history of substance abuse
  • Significant immunodeficiency due to underlying illness
  • History of stroke or transient ischemic attack, or diagnosis of cerebrovascular fibromuscular dysplasia
  • Clinically significant cardiovascular disease
  • Neurological syndromes, including multiple sclerosis, Alzheimer's disease, or Parkinson's disease
  • Uncontrolled fibromyalgia
  • History of left or right carotid surgery
  • History of unilateral or bilateral vagotomy, partial or complete splenectomy
  • Recurrent vasovagal syncope episodes
  • Current, regular use of tobacco products
  • Hypersensitivity/allergy to MRI contrast agents and/or unable to perform MRI

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04539964


Contacts
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Contact: Senior Manager of Clinical Operations at SetPoint Medical 855-737-3872 (855RESETRA) gautry@setpointmedical.com
Contact: Call Center for RESET-RA 855-737-3872 (855RESETRA)

Locations
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Sponsors and Collaborators
SetPoint Medical Corporation
Investigators
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Principal Investigator: Jeffrey R Curtis, MD MPH University of Alabama, Birmingham, AL
Principal Investigator: Mark Richardson, MD PhD Massachusetts General Hospital
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Responsible Party: SetPoint Medical Corporation
ClinicalTrials.gov Identifier: NCT04539964    
Other Study ID Numbers: SPM-020
First Posted: September 7, 2020    Key Record Dates
Last Update Posted: July 16, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No sharing data is planned.

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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
Keywords provided by SetPoint Medical Corporation:
Rheumatoid Arthritis
Vagus nerve
vagus nerve stimulating device
drug refractory
permanent implantable
implant
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents