A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H1: LY3819253 (LY-CoV555))
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 314
- 试验地点
- 114
- 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 LY3819253 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either LY3819253 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H1.
详细描述
This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of LY3819253 in hospitalized patients infected with COVID-19.
This is a randomized, blinded, controlled sub-study of LY3819253 plus current standard of care (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 LY3819253 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 Criteria:
- •Non-pregnant female participants who are of reproductive potential and male participants who are able to father a child must abstain from male/female sexual intercourse or agree to use two forms of effective contraception, where at least one form is highly effective (less than 1% failure rate), for the entirety of the study and for 90 days after investigational agent is administered. Highly effective methods of contraception (less than 1% failure rate) include, but are not limited to:
- •combination oral contraceptives
- •implanted contraceptives
- •intrauterine devices
- •Effective methods of contraception include, but are not limited to:
- •diaphragms and cervical caps with spermicide
- •cervical sponges
- •condoms with spermicide
- •Use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these barrier methods are combined.
- •Barrier protection methods without concomitant use of a spermicide are not an effective or acceptable method of contraception.
- •Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), and withdrawal are not acceptable methods of contraception. Participants not of reproductive potential are eligible without requiring the use of a contraceptive method. Participant-reported history is acceptable documentation of surgical sterilization and menopause. Participants with pregnant partners should use condoms during vaginal intercourse through 90 days after investigational agent administration. Participants should refrain from sperm donation through 90 days after investigational agent administration. NOTE: Reproductive potential is defined as patients who have reached menarche, who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥ 40 IU/ml or 24 consecutive months if an FSH is not available, who have not undergone surgical sterilization, who do not have other clinical condition that could induce amenorrhea, who are not taking medications such as oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators (SERMs) or chemotherapy that could induce amenorrhea. Individuals with permanent infertility due to an alternate medical cause (e.g. Mullerian agenesis, androgen insensitivity), investigator discretion should be applied.
结局指标
主要结局
Number of Participants With Sustained Recovery
时间窗: Through Day 90
Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
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 90(Through Day 90)
- Number of Participants Who Died From All Causes(Through Day 90)
- Number of Participants With a Safety Outcome Through Day 28(Through Day 28)