The SARS-CoV-2 Vaccine Response and Safety in Rheumatology Patients and the Influence of Temporary Interruptions in Immunomodulatory Therapy

Jeffrey Curtis8 个研究点分布在 1 个国家目标入组 841 人开始时间: 2021年11月15日最近更新: 2025年5月2日

适应症

干预措施

试验速览

阶段: 4 期
状态: 已完成
发起方
入组人数: 841
试验地点: 8
主要终点: Quantitative ratio post booster vs. pre-booster of IgG against SARS-CoV-2 using electrochemiluminescent (ECL) technology against the receptor binding domain (RBD) of spike protein, stratified by treatment arm

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The COVID-19 VaccinE Response in Rheumatology patients (COVER) study is a multicenter randomized controlled trial designed to evaluate the efficacy and safety of a mRNA COVID-19 vaccine supplemental dose (booster) in patients with autoimmune conditions and to evaluate the impact of different immunomodulatory therapies on vaccine response. The investigators propose to recruit up to 1000- patients with autoimmune conditions who have a completed 2-dose regime of mRNA COVID-19 vaccine (>28 days prior) and who are planning to receive an additional dose of mRNA COVID-19 vaccine (i.e., booster). Participants in this study will be men and women 18 years and older with confirmed rheumatic disease, including psoriatic arthritis (PsA), axial spondyloarthritis (SpA) and rheumatoid arthritis (RA) who express a decision to receive the mRNA vaccination booster within 30 days post enrollment.

A primary objective of this study is to test the hypothesis that holding certain medications for a brief period of time around the time of COVID-19 vaccination might improve the response to the vaccine while not unduly having safety concerns with respect to the effects of their disease. During the study, participants using the immunomodulatory therapies described outlined in protocol will be randomized to temporarily hold (for 2 weeks) versus continue after they receive the COVID-19 vaccine supplemental dose. Patients who temporarily stop one of their medications for their autoimmune inflammatory disease may be at increased risk of flares of their autoimmune condition. If these occur, they are expected to occur within 2 - 4 weeks of treatment interruption. Detailed protocol outlines the hold schedules for the therapies to be randomized in this study.

详细描述

There is an urgent need to determine the immunogenicity and safety of COVID-19 vaccines in people living with rheumatic disease on immunomodulatory therapies. Given the experience with influenza, pneumococcal, shingles, and other vaccinations in rheumatic disease populations, it is clear that disease modifying therapies (DMARDs) and the immunomodulatory therapies used to treat immune-mediated inflammatory diseases have the capacity to blunt immune responses to vaccinations. A number of mostly small studies have examined the optimal management of DMARDs with regard to the timing of vaccination in order to maximize the immunogenicity of various vaccines, with immunogenicity serving as a lab-based proxy for clinical effectiveness. As various development programs near completion with regard to a vaccine for SARS-CoV-2 virus, it will be imperative to understand how best to vaccinate immunosuppressed patients, and in particular, to optimize vaccine response resulting from a supplemental (booster) dose in those patients using immunomodulatory biologic and targeted small molecule therapies. In concert with the American College of Rheumatology's (ACR) task force focused on developing COVID-19 vaccination guidance, the proposed real-world study will address major knowledge gaps that exist with the SARS-CoV-2 vaccination in rheumatic disease patients who have not been included in vaccine studies. Currently, the ACR task force for COVID-19 vaccination guidance recommends that patients temporarily (1-2 weeks) stop one of their medications for their autoimmune inflammatory disease. However, it is not known if stopping medications may increase risk of flares in their autoimmune condition. If these occur, they are expected to occur within 2-4 weeks of treatment interruption.

Approximately 1000 patients will be studied to address these questions about the vaccine response following supplemental (booster) dosing associated with the use of upadacitinib, baricitinib, abatacept, canakinumab, secukinumab, ixekizumab, tofacitinib, TNFi, guselkumab (conditional on resource availability), and ustekinumab (conditional on resource availability). Participants will be randomized to hold these treatments for two weeks, or to continue their medication without interruption.

Study Objectives and Hypotheses

To conduct a large, randomized controlled trial to evaluate SARS-CoV-2 vaccine supplemental dose response in a large population of patients with autoimmune conditions, designed to meet three specific objectives and aims:

Specific Aim 1: Evaluate the immunogenicity of SARS-CoV-2 vaccination in patients with autoimmune conditions, randomizing patients to briefly interrupt (i.e., hold for 2 weeks) versus continue various immunomodulatory therapies at the time that they receive a supplemental (i.e., booster) mRNA vaccine dose.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Prevention
盲法: None

入排标准

年龄范围: 18 Years 至 85 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•*Patients must meet all of the inclusion criteria at the time of screening*
•Must have a rheumatology provider diagnosis of one or more of the following autoimmune inflammatory conditions:
•Rheumatoid arthritis or adults previously diagnosed with Juvenile idiopathic arthritis (analyzed as a single category)
•Psoriatic arthritis (PsA), Ankylosing spondylitis (ASp), or other Spondyloarthritis (SpA)
•Must have completed the 2-dose regimen of either of the two mRNA COVID-19 vaccines more than 28 days previous to enrollment
•Must be scheduled for an additional dose of mRNA COVID-19 vaccination booster (or with plans to schedule booster) within the next 30 days
•Must have a cell phone capable of receiving text messages, and/or a personal email address
•Currently receiving one of the medications described in Table 1
•Must be on stable immunomodulatory therapy for 8 weeks (with no dose changes, or interruptions > 2 weeks) prior to study enrollment. This would include both the qualifying immunomodulatory drug listed in Table 2, as well as any background immunomodulatory therapies (e.g. methotrexate, leflunomide) or glucocorticoids.
•Must be 18 years of age or older
•Must live in the United States.

排除标准

•• Already received a non-mRNA COVID-19 vaccine dose (J&J)
•Any use in the past 90 days of a monoclonal antibody against COVID-19 (e.g., bamlanivimab, casirivimab, imdevimab)
•Any known contraindication to COVID-19 vaccination, including allergic reaction to prior COVID-19 vaccination, and severe allergy to vaccine components (e.g., pegloticase)
•Known HIV/AIDS or any other immunodeficient condition
•Use of immunomodulatory therapy for any non-rheumatologic indication (e.g., organ transplantation)
•Currently receiving radiation or chemotherapy for any type of malignancy.
•Receipt of any immunization other than COVID-19 within two weeks prior to the COVID-19 vaccine supplemental dose
•Significant underlying illness that would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to < 1 year)
•Any other reason that, in the opinion of the site investigator, would interfere with required study related evaluations (e.g., uncontrolled disease flare, uncontrolled comorbidity)