PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)

COVID-19 Clinical 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05780541
• Other study ID #: 014/ACTIV-3/H6
• Status: Terminated
• Phase: Phase 3
• Start date: September 15, 2021
• Est. completion date: July 14, 2023

Study information

• Verified date: February 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 58
• Est. completion date: July 14, 2023
• Est. primary completion date: April 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• PF-07304814
PF-07304814 is a phosphate ester prodrug of PF-00835231 (active moiety), a potent and selective inhibitor of the SARS-CoV-2 3CLpro.
• Placebo
Commercially available 0.9% sodium chloride solution

Biological:
• Remdesivir
Antiviral agent

Locations

Country	Name	City	State
Denmark	Aalborg Hospital (Site 625-005), Hobrovej 18	Aalborg
Denmark	Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99	Aarhus N
Denmark	Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23	Copenhagen
Denmark	Righospitalet (Site 625-006), Blegdamsvej 9,	Copenhagen Ø
Denmark	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
United States	Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104	Bay Pines	Florida
United States	Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.	Boston	Massachusetts
United States	Massachusetts General Hospital (Site 202-002), 55 Fruit Street	Boston	Massachusetts
United States	MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214	Charleston	South Carolina
United States	Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street	Charleston	South Carolina
United States	Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304	Chula Vista	California
United States	Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.	Dallas	Texas
United States	Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd	Dallas	Texas
United States	UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor	Dallas	Texas
United States	National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street	Denver	Colorado
United States	Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.	Detroit	Michigan
United States	Duke University Hospital (Site 301-006), 2301 Erwin Road	Durham	North Carolina
United States	MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway	Florence	South Carolina
United States	Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard	Fort Wayne	Indiana
United States	Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive	Lebanon	New Hampshire
United States	Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.	Los Angeles	California
United States	Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way	Mather	California
United States	West Virginia University (Site 301-023), One Medical Center Drive	Morgantown	West Virginia
United States	Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway	New Orleans	Louisiana
United States	Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive	Newport Beach	California
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	Rhode Island Hospital (Site 080-036), 593 Eddy Street	Providence	Rhode Island
United States	The Miriam Hospital (Site 080-039), 164 Summit Ave.	Providence	Rhode Island
United States	UC Davis Health (Site 203-004), 2315 Stockton Blvd.	Sacramento	California
United States	University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207	Salt Lake City	Utah
United States	VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive	San Diego	California
United States	San Francisco VAMC (Site 074-002), 4150 Clement St.	San Francisco	California
United States	Hillsborough County Health Department, University of South Florida (Site 032-001)	Tampa	Florida
United States	MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.	Washington	District of Columbia
United States	West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue	West Haven	Connecticut

Sponsors (13)

Lead Sponsor

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

AIDS Clinical Trials Group, Cardiothoracic Surgical Trials Network, International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), Kirby Institute, Medical Research Council, National Heart, Lung, and Blood Institute (NHLBI), Pfizer, Prevention and Early Treatment of Acute Lung Injury, University of Copenhagen, University of Minnesota, US Department of Veterans Affairs, Washington D.C. Veterans Affairs Medical Center

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Recovery	Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.	Through Day 90
Primary	Number of Participants With an Ordinal Outcome on Day 5	Ordinal outcome with 7 mutually exclusive categories	Status on Day 5
Secondary	Number of Participants Who Died From All Causes	All-cause mortality	Through Day 90
Secondary	Number of Participants With a Safety Outcome Through Day 5	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5	Through Day 5
Secondary	Number of Participants With a Safety Outcome Through Day 28	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28	Through Day 28
Secondary	Number of Participants With a Safety Outcome Through Day 90	Death, SAE, clinical organ failure, serious infections through Day 90	Through Day 90