Multipart Exploratory Study to Evaluate Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 14
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
This study will evaluate the safety, tolerability, and effects of stimulating the splenic neurovascular bundle (NVB) with the Galvani System, which consists of a lead, implantable pulse generator, external components and accessories. The study will consist of 4 study periods, including a Randomized Control Trial period (Period 1), an Open Label period (Period 2), a Treat-to-target period (Period 3), and a Long-term Follow-up period (Period 4). Participants eligible for implant will have active rheumatoid arthritis (RA) and have an inadequate response or intolerance to at least two biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) or JAK inhibitors (JAKis). A sufficient number of participants will be enrolled so that approximately 28 participants will undergo device implantation.
详细描述
Participants with active rheumatoid arthritis (RA) who receive the implantable system will be randomly assigned to receive either active stimulation or sham-stimulation for 12 weeks (Period 1).
Following Period 1, all participants will enter an open label phase (Period 2) during which participants who responded to stimulation will continue on stimulation; whereas participants who received sham stimulation, or were stimulation non-responders, will receive a market-approved RA drug for 12 weeks.
At the end of Period 2, participants who respond to their Period 2 therapy but still exhibit signs and symptoms of RA will enter the Treat-to-target period (Period 3); others will proceed to Period 4 (Long-term Follow-up). During the Treat-to-Target period, participants will be treated with dual therapy (stimulation in combination with the market-approved RA drug) for up to 24 weeks.
Period 4 provides long term safety follow up for all study participants for a period of 5 years. Participants may receive stimulation in combination with other approved and standard of care therapies, subject to a favorable benefit-risk assessment in the judgement of the treating rheumatologist.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •RA of at least six months duration, per 2010 ACR/EULAR criteria
- •Male or female participants, 22-75 years of age
- •Active RA
- •Inadequate Response to at least 2 biologic DMARDs and/or JAK-inhibitors (JAKis) including at least one TNF inhibitor
- •Have an appropriate washout from previously used biological DMARDs or JAKi
- •Receiving current treatment with standard dose(s) of conventional synthetic DMARD(s) or have documented history of failure due to ineffectiveness or intolerance
排除标准
- •Inability to provide informed consent
- •Significant psychiatric disease or substance abuse
- •History of unilateral or bilateral vagotomy
- •Active or latent tuberculosis
- •Known infection with human immunodeficiency virus (HIV); current acute or chronic hepatitis B or hepatitis C; previous hepatitis B
- •Positive SARS COV 2 PCR screening test for COVID-19 infection (at the point of screening for this study)
- •Currently implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators)
- •Previous splenectomy
研究组 & 干预措施
RA drug combined with active stimulation, Period 3
Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks
干预措施: Background Treatment (Drug)
Active stimulation combined with RA drug, Period 3
Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks
干预措施: Active Stimulation (Device)
Active Stimulation; Period 1
Active stimulation for 12 weeks
干预措施: Active Stimulation (Device)
Active Stimulation; Period 1
Active stimulation for 12 weeks
干预措施: Background Treatment (Drug)
Sham Stimulation; Period 1
Sham stimulation for 12 weeks
干预措施: Sham Stimulation (Device)
Sham Stimulation; Period 1
Sham stimulation for 12 weeks
干预措施: Background Treatment (Drug)
RA drug combined with active stimulation, Period 3
Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks
干预措施: Baricitinib (Drug)
Open label active stimulation, Period 2
Open label active stimulation for 12 additional weeks
干预措施: Active Stimulation (Device)
Open label active stimulation, Period 2
Open label active stimulation for 12 additional weeks
干预措施: Background Treatment (Drug)
Open label RA Drug, Period 2
Open label drug treatment with baricitinib for 12 weeks
干预措施: Baricitinib (Drug)
Open label RA Drug, Period 2
Open label drug treatment with baricitinib for 12 weeks
干预措施: Background Treatment (Drug)
RA drug combined with active stimulation, Period 3
Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks
干预措施: Active Stimulation (Device)
Active stimulation combined with RA drug, Period 3
Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks
干预措施: Baricitinib (Drug)
Active stimulation combined with RA drug, Period 3
Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks
干预措施: Background Treatment (Drug)
Long-term Follow-up, Period 4
Standard of care treatments with or without stimulation
干预措施: Active Stimulation (Device)
Long-term Follow-up, Period 4
Standard of care treatments with or without stimulation
干预措施: Background Treatment (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: During Period 4 (Period 4 is up to 5 years in duration beyond Period 3)
Incidence of Adverse Events [Safety and Tolerability]
时间窗: Up through the end of Period 1 (Period 1 is up to 12 weeks duration)
Adverse Events (AEs) may include clinically significant findings from Laboratory Safety Assessments (clinical chemistry and hematology), vital signs (blood pressure, heart rate, respiratory rate, and body temperature), and 12-Lead EKG
次要结局
- Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score(Baseline to 12 weeks (Period 1))
- Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP)(Baseline to 12 weeks (Period 1))
- Change in the level of LPS-inducible release of TNFα in whole blood assay(Baseline to 24 weeks (Period 2))
- Change in the level of LPS-inducible release of IL-17 in whole blood assay(Baseline to 24 weeks (Period 2))
- Change in SF-36 mental component score(Baseline to 48 weeks (Period 3))
- To evaluate the usability of the external Galvani System devices and accessories(Through 48 weeks)
- Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFα) in whole blood assay(Baseline to 12 weeks (Period 1))
- Change in SF-36 physical component score(Baseline to 48 weeks (Period 3))
- Change in SF-36 domain score(Baseline to 48 weeks (Period 3))
- Evaluate device performance as assessed by tabulation of device deficiencies(Through 48 weeks)
- Incidence of a change in DAS28-CRP greater than 1.2 units in participants who are given Drug treatment with baricitinib during Period 2(week 12 to week 24)
- Incidence of participants who are given drug treatment with baricitinib achieving DAS28-CRP score <2.6 at the end of Period 2(Week 24)
- Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay(Baseline to 24 weeks (Period 2))
- Change in the level of LPS-inducible release of IL-8 in whole blood assay(Baseline to 24 weeks (Period 2))
- Change in DAS28-CRP(Baseline to 48 weeks (Period 3))
- Change in HAQ-DI score(Baseline to 48 weeks (Period 3))
- Change in Short Form 36 (SF-36) physical component score(Baseline to 12 weeks (Period 1))
- To evaluate the participants' perception of therapy and sensation(Through 48 weeks)
- Change in DAS28-CRP in participants who remain on active stimulation during Period 2(week 12 to week 24)
- Incidence of participants who remain on active stimulation achieving DAS28-CRP score <2.6 at the end of Period 2(Time Frame: Week 24)
- Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2(week 12 to week 24)