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

Sponsor
SetPoint Medical Corporation (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04539964
Collaborator
(none)
250
26
2
75.6
9.6
0.1

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated 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.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 :
Jan 11, 2021
Anticipated Primary Completion Date :
Nov 1, 2023
Anticipated Study Completion Date :
May 1, 2027

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Background therapy with conventional synthetic DMARD
  • Device: Non-active stimulation
    Non-active stimulation for 1 min once per day

    Outcome Measures

    Primary Outcome Measures

    1. the American College of Rheumatology (ACR) 20 response [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) [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 [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) [Week 12]

      HAQ-DI response based on the MCID of -0.22 from baseline

    4. ACR20 response at Week 12 from Day 0 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    22 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 Arizona Arthritis Rheumatology & Research, PLLC Phoenix Arizona United States 85037
    3 Medvin Clinical Research Covina California United States 91722
    4 Inland Rheumatology Clinical Trials Upland California United States 91786
    5 Medvin Clinical Research Whittier California United States 90602
    6 Stamford Therapeutics Consortium Stamford Connecticut United States 06905
    7 Delaware Arthritis Lewes Delaware United States 19958
    8 IRIS Research and Development Plantation Florida United States 33324
    9 West Broward Rheumatology Associates Tamarac Florida United States 33321
    10 Florida Medical Clinic, LLC Zephyrhills Florida United States 33542
    11 Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology Boston Massachusetts United States 02114
    12 June DO, PC Lansing Michigan United States 48910
    13 Albuquerque Center for Rheumatology Albuquerque New Mexico United States 87102
    14 DJL Clinical Research Charlotte North Carolina United States 28210
    15 PMG Research Hickory North Carolina United States 28601
    16 Health Research of Oklahoma, PLLC Oklahoma City Oklahoma United States 73103
    17 Altoona Center for Clinical Research Duncansville Pennsylvania United States 16635
    18 West Tennessee Research Institute Jackson Tennessee United States 38305
    19 Austin Regional Clinic Austin Texas United States 78717
    20 Tekton Research Austin Texas United States 78745
    21 Southwest Rheumatology Research LLC Mesquite Texas United States 75150
    22 Clinical Trials of Texas, Inc San Antonio Texas United States 78229
    23 Western Washington Arthritis Clinic Bothell Washington United States 98021
    24 Arthritis Northwest Rheumatology, PLLC Spokane Washington United States 99204
    25 University Physicians and Surgeons, INC dba Marshall Health Huntington West Virginia United States 25701
    26 West Virginia University Morgantown West Virginia United States 26506

    Sponsors and Collaborators

    • SetPoint Medical Corporation

    Investigators

    • Principal Investigator: Jeffrey R Curtis, MD MPH, University of Alabama, Birmingham, AL
    • Principal Investigator: Mark Richardson, MD PhD, Massachusetts General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SetPoint Medical Corporation
    ClinicalTrials.gov Identifier:
    NCT04539964
    Other Study ID Numbers:
    • SPM-020
    First Posted:
    Sep 7, 2020
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by SetPoint Medical Corporation
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 15, 2022