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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
243
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.
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
Active stimulation for 1 min once per day
Non-active stimulation for 1 min once per day
Arizona Arthritis ans Rheumatology Research, PPLC
Mesa, Arizona, United States
Arizona Arthritis Rheumatology & Research, PLLC
Phoenix, Arizona, United States
Arizona Arthritis & Rheumatology Research, PLLC
Tucson, Arizona, United States
Medvin Clinical Research
Covina, California, United States
Inland Rheumatology Clinical Trials
Upland, California, United States
the American College of Rheumatology (ACR) 20 Response
Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) 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=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).
Time frame: Week 12
DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR)
The Disease Activity Score in 28 joints calculated with C-reactive protein (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=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 A subject is considered having a moderate treatment response if: * DAS28-CRP score improvement from baseline to Week 12 is \> 0.6 and ≤ 1.2, and the DAS28-CRP score at Week 12 is ≤ 5.1; or * DAS28-CRP score improvement from baseline to Week 12 is \> 1.2, and the DAS28-CRP score at Week 12 is \> 3.2. A subject is considered having a good treatment response if: • DAS28-CRP score improvement from baseline to Week 12 is \> 1.2 and the DAS28-CRP score at Week 12 is ≤ 3.2
Time frame: Week 12
DAS28-CRP Response (MCID -1.2) at Week 12
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) response is based on the minimal clinically important difference (MCID) of -1.2 from baseline. DAS28-CRP is based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96
Time frame: Week 12
Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22)
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 12
ACR20 Response at Week 12 From Day 0
Response is defined as achieving at least 20% improvement from Day 0 to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) 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=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL).
Time frame: Week 12
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Medvin Clinical Research
Whittier, California, United States
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Fort Collins, Colorado, United States
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Lewes, Delaware, United States
Arthritis & Rheumatic Disease Specialties
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