Vagus Nerve Stimulation for Moderate to Severe Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— RESET-RA  

Official title:

Vagus Nerve Stimulation Using the SetPoint System for Moderate to Severe Rheumatoid Arthritis: The RESET-RA Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04539964
• Other study ID #: SPM-020
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 11, 2021
• Est. completion date: October 2027

Study information

• Verified date: February 2024
• Source: SetPoint Medical Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: October 2027
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• 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.

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

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

Locations

Country	Name	City	State
United States	Albuquerque Center for Rheumatology	Albuquerque	New Mexico
United States	Arthritis & Rheumatology Research Institute, PLLC	Allen	Texas
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Augusta University	Augusta	Georgia
United States	Austin Regional Clinic	Austin	Texas
United States	Central Texas Rheumatology Associates	Austin	Texas
United States	Tekton Research	Austin	Texas
United States	Arthritis & Rheumatic Disease Specialties	Aventura	Florida
United States	HARAC Research Corporation	Avon Park	Florida
United States	Long Island Regional Arthritis & Osteoporosis Care	Babylon	New York
United States	Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology	Boston	Massachusetts
United States	Sound Clinical Research, LLC	Bothell	Washington
United States	RecioMed Clinical Research Network, Inc.	Boynton Beach	Florida
United States	DJL Clinical Research	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Bay Area Rheumatology	Clearwater	Florida
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	Medvin Clinical Research	Covina	California
United States	Saint Paul Rheumatology, P.A.	Eagan	Minnesota
United States	Annapolis Rheumatology	Fairfax	Virginia
United States	The Arthritis & Rheumatology Clinic of Northern Colorado	Fort Collins	Colorado
United States	Hinsdale Orthopaedics Illinois Bone and Joint Institute	Hinsdale	Illinois
United States	Biopharma Informatic	Houston	Texas
United States	Kansas City Physician Partners	Kansas City	Missouri
United States	June DO, PC	Lansing	Michigan
United States	Parris and Associates Rheumatology	Lawrenceville	Georgia
United States	Delaware Arthritis	Lewes	Delaware
United States	Physician Research Collaboration, LLC	Lincoln	Nebraska
United States	Arizona Arthritis ans Rheumatology Research, PPLC	Mesa	Arizona
United States	Southwest Rheumatology Research LLC	Mesquite	Texas
United States	West Virginia University	Morgantown	West Virginia
United States	Health Research of Oklahoma, PLLC	Oklahoma City	Oklahoma
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Arizona Arthritis Rheumatology & Research, PLLC	Phoenix	Arizona
United States	IRIS Research and Development	Plantation	Florida
United States	West County Rheumatology	Saint Louis	Missouri
United States	Clinical Trials of Texas, Inc	San Antonio	Texas
United States	Stamford Therapeutics Consortium	Stamford	Connecticut
United States	Arizona Arthritis & Rheumatology Research, PLLC	Tucson	Arizona
United States	Inland Rheumatology Clinical Trials	Upland	California
United States	Medvin Clinical Research	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
SetPoint Medical Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the American College of Rheumatology (ACR) 20 response	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.	Week 12
Secondary	The Disease Activity Score 28-C-reactive protein (DAS28-CRP) good or moderate response as defined by European League Against Rheumatism (EULAR)	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	Week 12
Secondary	DAS28-CRP response (MCID -1.2) at Week 12	DAS28-CRP response based on the minimal clinically important difference (MCID) of -1.2 from baseline	Week 12
Secondary	Health Assessment Questionnaire Disability Index (HAQ-DI) response (MCID -0.22)	HAQ-DI response based on the MCID of -0.22 from baseline	Week 12
Secondary	ACR20 response at Week 12 from Day 0	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.	Week 12