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

• ClinicalTrials.gov Identifier: NCT04539964
• Recruitment Status: Active, not recruiting
• First Posted: September 7, 2020
• Last Update Posted: February 28, 2024
• Sponsor: SetPoint Medical Corporation
• Information provided by (Responsible Party): SetPoint Medical Corporation

Tracking Information

• First Submitted Date: August 31, 2020
• First Posted Date: September 7, 2020
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: January 11, 2021
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 16, 2020)

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.

Original Primary Outcome Measures (submitted: August 31, 2020)

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 20% improvement from baseline in tender and swollen joint counts of 28 joints and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0 to 3), subject global assessment (VAS 0-100 mm), subject pain (VAS 0-100 mm), evaluator's global assessment (VAS 0-100 mm), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL).

Current Secondary Outcome Measures (submitted: November 16, 2020)

• 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
• 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
• 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
• 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.

Original Secondary Outcome Measures (submitted: August 31, 2020)

• 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 is based on a composite score of 4 items: tender and swollen joint counts of 28 joints, subject global assessment (VAS 0-100) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L), as defined by EULAR.
• DAS28-CRP response (MCID -1.2) at Week 12 [ Time Frame: Week 12 ]
  The DAS28-CRP response is based on the minimal clinically important difference (MCID) of -1.2 from baseline.
• 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.
• HAQ-DI score change [ Time Frame: Week 12 ]
  HAQ-DI score change from baseline.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vagus Nerve Stimulation for Moderate to Severe Rheumatoid Arthritis
• Official Title: Vagus Nerve Stimulation Using the SetPoint System for Moderate to Severe Rheumatoid Arthritis: The RESET-RA Study
• 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: Rheumatoid Arthritis

Intervention

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

Study Arms

• Experimental: Treatment
  Active stimulation for 1 min once per day
  Interventions:

  • Procedure: Implant Procedure
  • Drug: Conventional Synthetic DMARD
  • Device: Active stimulation
• Sham Comparator: Control
  Non-active stimulation for 1 min once per day
  Interventions:

  • Procedure: Implant Procedure
  • Drug: Conventional Synthetic DMARD
  • Device: Non-active stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 31, 2020): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2027
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 22 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04539964
• Other Study ID Numbers: SPM-020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No sharing data is planned.

• Current Responsible Party: SetPoint Medical Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: SetPoint Medical Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Tesser, MD; Arizona Arthritis and Rheumatology Research, P.C.
• Principal Investigator: Mark Richardson, MD PhD; Massachusetts General Hospital

• PRS Account: SetPoint Medical Corporation
• Verification Date: February 2024