Clinical trial NCT05780541: PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)
Official title: A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H6: PF-07304814)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: COVID-19
COVID 19
Coronaviridae Infections
Coronavirus Infections
RNA Virus Infections
Virus Diseases
Nidovirales Infections
SARS-CoV-2
SARS Coronavirus
ACTIV-3
ACTIV3
TICO
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
name: University of Copenhagen
name: Medical Research Council
name: Kirby Institute
name: Washington D.C. Veterans Affairs Medical Center
name: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
name: National Heart, Lung, and Blood Institute (NHLBI)
name: US Department of Veterans Affairs
name: Prevention and Early Treatment of Acute Lung Injury
name: Cardiothoracic Surgical Trials Network
name: Pfizer
name: University of Minnesota
First posted: 2023-03-22
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria: Refer to the master protocol (NCT04501978)

Exclusion Criteria: Refer to the master protocol (NCT04501978)

Additional Exclusion Criteria:

1. Participants with moderate to severe hepatic impairment (i.e. Child-Pugh class B or C) or acute liver failure.
2. Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4 (see Section H6.3.4).
3. 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.
4. Pregnant women
5. Nursing mothers
6. 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.
7. 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.
8. 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.

Primary outcomes:
measure: Number of Participants With Sustained Recovery
timeFrame: Through Day 90
measure: Number of Participants With an Ordinal Outcome on Day 5
timeFrame: Status on Day 5
Secondary outcomes:
measure: Number of Participants Who Died From All Causes
timeFrame: Through Day 90
measure: Number of Participants With a Safety Outcome Through Day 5
timeFrame: Through Day 5
measure: Number of Participants With a Safety Outcome Through Day 28
timeFrame: Through Day 28
measure: Number of Participants With a Safety Outcome Through Day 90
timeFrame: Through Day 90
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
state: California
city: Mather
country: United States
facility: Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive
state: California
city: Palo Alto
country: United States
facility: Palo Alto VAMC (Site 074-005), 3801 Miranda Avenue
state: California
city: Sacramento
country: United States
facility: UC Davis Health (Site 203-004), 2315 Stockton Blvd.
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC (Site 074-002), 4150 Clement St.
state: California
city: Denver
country: United States
facility: National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street
state: Colorado
city: West Haven
country: United States
facility: West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.
state: District of Columbia
city: Bay Pines
country: United States
facility: Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Department, University of South Florida (Site 032-001)
state: Florida
city: Fort Wayne
country: United States
facility: Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital (Site 202-002), 55 Fruit Street
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
state: New Hampshire
city: Durham
country: United States
facility: Duke University Hospital (Site 301-006), 2301 Erwin Road
state: North Carolina
city: Portland
country: United States
facility: Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital (Site 080-036), 593 Eddy Street
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital (Site 080-039), 164 Summit Ave.
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street
state: South Carolina
city: Charleston
country: United States
facility: MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214
state: South Carolina
city: Florence
country: United States
facility: MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway
state: South Carolina
city: Dallas
country: United States
facility: Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
state: Texas
city: Dallas
country: United States
facility: Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
state: Utah
city: Morgantown
country: United States
facility: West Virginia University (Site 301-023), One Medical Center Drive
state: West Virginia
city: Aalborg
country: Denmark
facility: Aalborg Hospital (Site 625-005), Hobrovej 18
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
city: Copenhagen Ø
country: Denmark
facility: Righospitalet (Site 625-006), Blegdamsvej 9,
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23
city: Herlev
country: Denmark
facility: Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
city: Kolding
country: Denmark
facility: Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
city: Odense
country: Denmark
facility: Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10
Study officials:
affiliation: INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
name: Jens Lundgren, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: INSIGHT Statistical and Data Management Center, University of Minnesota
name: James Neaton, Prof.
role: STUDY_CHAIR
References: