Vagus Nerve Stimulation Using the SetPoint System for Moderate to Severe Rheumatoid Arthritis: The RESET-RA Study
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 243
- 试验地点
- 81
- 主要终点
- the American College of Rheumatology (ACR) 20 Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 22 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Treatment
Active stimulation for 1 min once per day
干预措施: Implant Procedure (Procedure)
Treatment
Active stimulation for 1 min once per day
干预措施: Conventional Synthetic DMARD (Drug)
Treatment
Active stimulation for 1 min once per day
干预措施: Active stimulation (Device)
Control
Non-active stimulation for 1 min once per day
干预措施: Implant Procedure (Procedure)
Control
Non-active stimulation for 1 min once per day
干预措施: Conventional Synthetic DMARD (Drug)
Control
Non-active stimulation for 1 min once per day
干预措施: Non-active stimulation (Device)
结局指标
主要结局
the American College of Rheumatology (ACR) 20 Response
时间窗: Week 12
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).
次要结局
- DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR)(Week 12)
- DAS28-CRP Response (MCID -1.2) at Week 12(Week 12)
- Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22)(Week 12)
- ACR20 Response at Week 12 From Day 0(Week 12)