PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)
- Conditions
- COVID-19
- Interventions
- Registration Number
- NCT05780541
- Brief Summary
This study looks at the safety and effectiveness of PF-07304814 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either PF-07304814 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H6.
- Detailed Description
This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of PF-07304814 in hospitalized patients infected with COVID-19.
This is a randomized, blinded, controlled sub-study of PF-07304814 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 PF-07304814 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
- TERMINATED
- Sex
- All
- Target Recruitment
- 58
Refer to the master protocol (NCT04501978)
Refer to the master protocol (NCT04501978)
Additional Exclusion Criteria:
-
Participants with moderate to severe hepatic impairment (i.e. Child-Pugh class B or C) or acute liver failure.
-
Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4 (see Section H6.3.4).
-
Patients will be excluded if taking drugs which have a narrow therapeutic window that are substrates of CYP3A4, including but not limited to: astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus, and terfenadine.
-
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 5 weeks 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 5 weeks of the study.
-
Patients with a history of deep vein thrombosis or pulmonary thrombotic embolism*.
- Prior to the initial futility assessment, which is performed when approximately 150 patients have been enrolled on PF-07304814 and 150 on placebo, patients with a history of deep vein thrombosis or pulmonary embolism will be excluded. These patients will be eligible for the trial if the initial futility assessment is passed by this agent, and if risk-benefit is favorable based on an assessment of available data that is reviewed by the independent DSMB. These data will include treatment comparisons of thromboembolic events and coagulation markers, and any additional data from studies carried out by Pfizer.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-07304814 plus SOC PF-07304814 * PF-07304814 250 mg per day for 5 days; administered as a constant rate IV infusion * Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion PF-07304814 plus SOC Remdesivir * PF-07304814 250 mg per day for 5 days; administered as a constant rate 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 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 Status on Day 5 Ordinal outcome with 7 mutually exclusive categories
- Secondary Outcome Measures
Name Time Method Number of Participants Who Died From All Causes Through Day 90 All-cause mortality
Number of Participants With a Safety Outcome Through Day 5 Through Day 5 Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5
Number of Participants With a Safety Outcome Through Day 28 Through Day 28 Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28
Number of Participants With a Safety Outcome Through Day 90 Through Day 90 Death, SAE, clinical organ failure, serious infections through Day 90
Trial Locations
- Locations (40)
VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive
🇺🇸San Diego, California, United States
University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
🇺🇸Salt Lake City, Utah, United States
Duke University Hospital (Site 301-006), 2301 Erwin Road
🇺🇸Durham, North Carolina, United States
Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
🇩🇰Herlev, Denmark
Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
🇩🇰Hillerød, Denmark
Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
🇩🇰Kolding, Denmark
Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
🇩🇰Odense, Denmark
Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10
🇩🇰Roskilde, Denmark
Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
🇺🇸Detroit, Michigan, United States
National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street
🇺🇸Denver, Colorado, United States
Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way
🇺🇸Mather, California, United States
Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304
🇺🇸Chula Vista, California, United States
Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive
🇺🇸Newport Beach, California, United States
Massachusetts General Hospital (Site 202-002), 55 Fruit Street
🇺🇸Boston, Massachusetts, United States
Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
🇺🇸Los Angeles, California, United States
San Francisco VAMC (Site 074-002), 4150 Clement St.
🇺🇸San Francisco, California, United States
Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
🇩🇰Aarhus N, Denmark
The Miriam Hospital (Site 080-039), 164 Summit Ave.
🇺🇸Providence, Rhode Island, United States
Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.
🇺🇸Boston, Massachusetts, United States
Righospitalet (Site 625-006), Blegdamsvej 9,
🇩🇰Copenhagen Ø, Denmark
Rhode Island Hospital (Site 080-036), 593 Eddy Street
🇺🇸Providence, Rhode Island, United States
Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
🇺🇸Dallas, Texas, United States
Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
🇺🇸Lebanon, New Hampshire, United States
Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd
🇺🇸Dallas, Texas, United States
MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway
🇺🇸Florence, South Carolina, United States
Aalborg Hospital (Site 625-005), Hobrovej 18
🇩🇰Aalborg, Denmark
UC Davis Health (Site 203-004), 2315 Stockton Blvd.
🇺🇸Sacramento, California, United States
Hillsborough County Health Department, University of South Florida (Site 032-001)
🇺🇸Tampa, Florida, United States
West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue
🇺🇸West Haven, Connecticut, United States
MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.
🇺🇸Washington, District of Columbia, United States
Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
🇺🇸Fort Wayne, Indiana, United States
Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104
🇺🇸Bay Pines, Florida, United States
UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
🇺🇸Dallas, Texas, United States
Palo Alto VAMC (Site 074-005), 3801 Miranda Avenue
🇺🇸Palo Alto, California, United States
Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road
🇺🇸Portland, Oregon, United States
West Virginia University (Site 301-023), One Medical Center Drive
🇺🇸Morgantown, West Virginia, United States
Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23
🇩🇰Copenhagen, Denmark
Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street
🇺🇸Charleston, South Carolina, United States
Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
🇺🇸New Orleans, Louisiana, United States
MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214
🇺🇸Charleston, South Carolina, United States