AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)
- Conditions
- COVID-19
- Interventions
- Registration Number
- NCT05780437
- Brief Summary
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.
- Detailed Description
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.
This trial will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1455
• Refer to the master protocol (NCT04501978)
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Refer to the master protocol (NCT04501978)
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD7442 plus SOC Remdesivir * 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 AZD7442 plus SOC AZD7442 * 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 Placebo plus SOC Placebo * Placebo administered by IV infusion * Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion Placebo plus SOC Remdesivir * Placebo administered by IV infusion * Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion
- Primary Outcome Measures
Name Time Method Number of Participants With Sustained Recovery 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 Status on Day 5 Ordinal outcome with 7 mutually exclusive categories
- Secondary Outcome Measures
Name Time Method Number of Participants With a Safety Outcome Through Day 5 Through Day 5 Safety outcomes are defined as Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5. Seriousness was based on the definition of the term at 21CFR312.32
AEs were graded for severity by the treating investigator, according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (also known at the DAIDS AE Grading Table), U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. \[July 2017\]. Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf). The following generic grading descriptions from the DAIDS AE Grading Table are provided for context: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threateningNumber of Participants With a Safety Outcome Through Day 28 Through Day 28 Safety outcomes are defined as Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28. Seriousness was based on the definition of the term at 21CFR312.32
AEs were graded for severity by the treating investigator, according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (also known at the DAIDS AE Grading Table), U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. \[July 2017\]. Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf). The following generic grading descriptions from the DAIDS AE Grading Table are provided for context: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threateningNumber of Participants With a Safety Outcome Through Day 90 Through Day 90 Safety outcomes are defined as Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 90. Seriousness was based on the definition of the term at 21CFR312.32
AEs were graded for severity according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (also known at the DAIDS AE Grading Table).Number of Participants Who Died From All Causes Through Day 90 All-cause Mortality
Trial Locations
- Locations (124)
Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
🇺🇸Tucson, Arizona, United States
Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.
🇺🇸Tucson, Arizona, United States
Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304
🇺🇸Chula Vista, California, United States
Community Regional Medical Center (Site 203-005), 2823 Fresno Street
🇺🇸Fresno, California, United States
Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1
🇺🇸La Mesa, California, United States
VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
🇺🇸Loma Linda, California, United States
VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)
🇺🇸Long Beach, California, United States
Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
🇺🇸Los Angeles, California, United States
Scroll for more (114 remaining)Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue🇺🇸Tucson, Arizona, United States