Clinical trial NCT04539964: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Vagus nerve
vagus nerve stimulating device
drug refractory
permanent implantable
implant
Lead sponsor: SetPoint Medical Corporation
Sponsor class: INDUSTRY
First posted: 2020-09-07
Enrollment: 243
Sex: ALL
Minimum age (years): 22
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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 up to 250 subjects at up to 45 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 252-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 up to 250 subjects at up to 45 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 252-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.

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

Primary outcomes:
measure: the American College of Rheumatology (ACR) 20 response
timeFrame: Week 12
Secondary outcomes:
measure: The Disease Activity Score 28-C-reactive protein (DAS28-CRP) good or moderate response as defined by European League Against Rheumatism (EULAR)
timeFrame: Week 12
measure: DAS28-CRP response (MCID -1.2) at Week 12
timeFrame: Week 12
measure: Health Assessment Questionnaire Disability Index (HAQ-DI) response (MCID -0.22)
timeFrame: Week 12
measure: ACR20 response at Week 12 from Day 0
timeFrame: Week 12
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Arizona Arthritis ans Rheumatology Research, PPLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis Rheumatology & Research, PLLC
state: Arizona
city: Tucson
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials
state: California
city: Whittier
country: United States
facility: Medvin Clinical Research
state: California
city: Fort Collins
country: United States
facility: The Arthritis & Rheumatology Clinic of Northern Colorado
state: Colorado
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Lewes
country: United States
facility: Delaware Arthritis
state: Delaware
city: Aventura
country: United States
facility: Arthritis & Rheumatic Disease Specialties
state: Florida
city: Avon Park
country: United States
facility: HARAC Research Corporation
state: Florida
city: Boynton Beach
country: United States
facility: RecioMed Clinical Research Network, Inc.
state: Florida
city: Clearwater
country: United States
facility: Bay Area Rheumatology
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Lawrenceville
country: United States
facility: Parris and Associates Rheumatology
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Willowbrook
country: United States
facility: Willow Rheumatology and Wellness PLLC
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology
state: Massachusetts
city: Lansing
country: United States
facility: June DO, PC
state: Michigan
city: Eagan
country: United States
facility: Saint Paul Rheumatology, P.A.
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Physician Partners
state: Missouri
city: Saint Louis
country: United States
facility: West County Rheumatology
state: Missouri
city: Lincoln
country: United States
facility: Physician Research Collaboration, LLC
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque Center for Rheumatology
state: New Mexico
city: Babylon
country: United States
facility: Long Island Regional Arthritis & Osteoporosis Care
state: New York
city: Charlotte
country: United States
facility: DJL Clinical Research
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma, PLLC
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Allen
country: United States
facility: Arthritis & Rheumatology Research Institute, PLLC
state: Texas
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Austin
country: United States
facility: Central Texas Rheumatology Associates
state: Texas
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc
state: Texas
city: Fairfax
country: United States
facility: Annapolis Rheumatology
state: Virginia
city: Bothell
country: United States
facility: Sound Clinical Research, LLC
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Arizona Arthritis and Rheumatology Research, P.C.
name: John Tesser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Mark Richardson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: