SARS-CoV-2 Vaccination Strategies in Previously Hospitalized and Recovered COVID-19 Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 55
- 主要终点
- Ratio of 48-Week to Baseline Neutralizing Antibody (NAb) Levels
研究概览
简要总结
In this Phase 4, open-label trial, participants of the ACTIV-3/TICO clinical trial at selected sites who received certain pre-specified blinded investigational agents or placebo as part of that trial, and who have since achieved sustained recovery, and who are still [TICO assignment] blinded and who are still within 28 to 90 days after initial TICO randomization, will be randomized in this 2x2 factorial design to one of four groups: (i) immediate versus 12 week deferral of first dose administration and also (ii) one dose only, versus two doses to be given 4 weeks apart of the Moderna mRNA-1273 or the Pfizer BNT162b2 vaccine (mRNA vaccines).
Choice of Moderna or Pfizer vaccine is determined based on availability at the site. The choice is individual, although participants vaccinated twice should receive the same type of vaccine for both injections. The primary objectives of this 2x2 factorial design are (i) to estimate the difference in neutralizing antibody (NAb) response to the mRNA vaccine from baseline to Week 48 among participants vaccinated early versus deferred, and (ii) to estimate the difference in NAb response to this vaccine among participants vaccinated once versus twice. The primary analyses will be carried out in participants randomized to placebo in TICO. Analyses will also be carried out for those who receive the investigational agent(s) studied in TICO.
A key secondary objective is to ascertain the effect, if any, of SARS-CoV-2 monoclonal antibodies, and other interventions that have been studied in hospitalized COVID-19 subjects, on natural and vaccine-induced immunity.
Participants will remain blinded to the interventions received in the ACTIV-3/TICO study, however allocation to the timing of vaccination and to one or two vaccinations in this (VATICO) study is not blinded.
详细描述
In this Phase 4 trial, participants in the TICO master protocol who received certain pre-specified blinded investigational agents or matched placebos will be offered enrollment, with the understanding that this will require 2X2 randomized assignment of the timing and of the number of mRNA SARS-CoV-2 vaccinations to be received, via publicly-available mRNA SARS-CoV-2 vaccination sites or via other routes, in keeping with the 4 specified study arm assignments.
This will address the objective of evaluating if the vaccine is best administered early or deferred after recovery, and whether one injection provides comparable immune response to a two-injection course of vaccination. Participants (as well as the protocol team) will remain blinded to the interventions studied in TICO. Allocation to timing of vaccination and to one or two vaccinations is not blinded. Participants will be offered enrollment in this protocol at the Day 28 or Day 90 visits in TICO, or anytime between these visits.
Participants will have blood collected for research purposes at the time of enrollment and at Weeks 12, 24, and 48.
The study vaccine and regimen will not be blinded; there will be be no 'dummy/placebo' vaccine administered. Vaccines are expected to be made available either through the study directly, or through a reliable public vaccination program using vaccine available per the local regulatory mechanism (e.g., currently under Emergency Use Authorization (EUA) for the United States) or via other routes in case such local mechanisms are not available.
Participants will be equally allocated to 4 groups to inform each of two vaccine strategies:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participating in the ACTIV-3/TICO trial and received a selected blinded investigational agent, or placebo for that agent, at selected sites.
- •Willingness to strictly adhere to the randomly allocated dosage number and schedule for vaccine administration.
- •Participant is between Day 28 and Day 90 TICO visits inclusive at time of randomization.
- •At time of screening for this study, has experienced sustained recovery (i.e., the primary endpoint in TICO) for at least two consecutive weeks, i.e. having returned uninterrupted to the person's premorbid living facility (or equivalent) for at least 2 consecutive weeks.
- •Ability and willingness of participant (or legally authorized representative) to provide informed consent prior to initiation of any study procedures.
排除标准
- •Receipt of a SARS-CoV-2 (COVID-19) vaccine after enrollment into TICO. Participants who received a SARS-CoV-2 vaccine prior to enrollment in TICO may be enrolled in this study.
- •Known allergy to any component of the study eligible vaccine(s).
结局指标
主要结局
Ratio of 48-Week to Baseline Neutralizing Antibody (NAb) Levels
时间窗: Pre-vaccination baseline and 48 weeks post-vaccination
Change in antibody level as measured by ratio of follow-up to baseline level
次要结局
- Ratio of 12-Week to Baseline Neutralizing Antibody (NAb) Levels(Pre-vaccination baseline and 12 weeks post-vaccination)
- Ratio of 24-Week to Baseline Neutralizing Antibody (NAb) Levels(Pre-vaccination baseline and 24 weeks post-vaccination)
- Number of Deaths(Through Week 24 after enrollment)
- Number of Serious Adverse Events (SAEs)(Through Week 24)
- Number of Patients Non-adherent to 2nd Dose(Second vaccine doses were due at 4 and 16 weeks after randomization in Arm 2 and 4, respectively)
- Number of Patients Non-adherent to Assigned Treatment Strategy(Vaccine doses were due through 16-weeks post-randomization; participants were followed for vaccination status through 48 weeks post-randomization)
- Percent of Patients With >=4-fold Difference in NAb(Pre-vaccination baseline and 48 weeks post-vaccination)