A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H4: AZD7442)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,455
- 试验地点
- 124
- 主要终点
- Number of Participants With Sustained Recovery
研究概览
简要总结
This study looks at the safety and effectiveness of AZD7442 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a AZD7442 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H4.
详细描述
This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of AZD7442 in hospitalized patients infected with COVID-19.
This is a randomized, blinded, controlled sub-study of AZD7442 plus current SOC against placebo plus current SOC. The placebo arm may be shared across other sub-studies of the ACTIV-3/TICO master protocol. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.
Randomization will be stratified by study site pharmacy and disease severity. There are 2 disease severity strata: participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2).
An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. The pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. At the outset of the trial, only participants in disease severity stratum 1 will be enrolled. This will continue until approximately 300 participants are enrolled and followed for 5 days. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5.
If AZD7442 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. Participants will be followed for 18 months following randomization.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Refer to the master protocol (NCT04501978)
排除标准
- •Refer to the master protocol (NCT04501978)
- •Additional Exclusion Criteria:
- •Pregnant women
- •Nursing mothers
- •Women of child-bearing potential who are unwilling to acknowledge the strong advice to abstain from sexual intercourse with men or practice appropriate contraception through the entire 18 months of the study
- •Men who are unwilling to acknowledge the strong advice to abstain from sexual intercourse with women of child-bearing potential or to use barrier contraception through the entire 18 months of the study.
- •In addition, prior to the initial futility assessment which is performed when approximately 150 participants have been enrolled on AZD7442 and 150 on placebo, patients on high-flow oxygen or non-invasive ventilation (category 5 of the pulmonary ordinal outcome) will be excluded. These patients may be eligible for the trial if the initial futility assessment is passed by this agent.
研究组 & 干预措施
AZD7442 plus SOC
- AZD7442 600 mg solution (4 separate vials, 2 containing 150 mg each of AZD88995 and 2 containing 150 mg each of AZD1061); administered by IV infusion
- Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion
干预措施: AZD7442 (Biological)
AZD7442 plus SOC
- AZD7442 600 mg solution (4 separate vials, 2 containing 150 mg each of AZD88995 and 2 containing 150 mg each of AZD1061); administered by IV infusion
- Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion
干预措施: Remdesivir (Biological)
Placebo plus SOC
- Placebo administered by IV infusion
- Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion
干预措施: Placebo (Biological)
Placebo plus SOC
- Placebo administered by IV infusion
- Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion
干预措施: Remdesivir (Biological)
结局指标
主要结局
Number of Participants With Sustained Recovery
时间窗: Through Day 90
The primary endpoint is the proportion of subjects with sustained recovery, which is defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90. Home is defined as the level of residence or facility where the participant was residing prior to hospital admission leading to enrollment in this protocol. Readmission from "home" may occur, and if this occurs within 14 days of the first discharge to "home," then the primary endpoint will not be reached until such time as the participant has been at home for 14 consecutive days.
Number of Participants With an Ordinal Outcome on Day 5
时间窗: Status on Day 5
Ordinal outcome with 7 mutually exclusive categories
次要结局
- Number of Participants With a Safety Outcome Through Day 5(Through Day 5)
- Number of Participants With a Safety Outcome Through Day 28(Through Day 28)
- Number of Participants With a Safety Outcome Through Day 90(Through Day 90)
- Number of Participants Who Died From All Causes(Through Day 90)