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

NCT ID: NCT05780541

Last Updated: 2024-02-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-15
• Study Completion Date: 2023-07-14

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

PF-07304814 plus SOC

• 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

Group Type: EXPERIMENTAL

PF-07304814

Intervention Type: DRUG

PF-07304814 is a phosphate ester prodrug of PF-00835231 (active moiety), a potent and selective inhibitor of the SARS-CoV-2 3CLpro.

Remdesivir

Intervention Type: BIOLOGICAL

Antiviral agent

Placebo plus SOC

• Placebo administered by IV infusion
• Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Commercially available 0.9% sodium chloride solution

Remdesivir

Intervention Type: BIOLOGICAL

Antiviral agent

Interventions

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.

Intervention Type: DRUG

Placebo

Commercially available 0.9% sodium chloride solution

Intervention Type: DRUG

Remdesivir

Antiviral agent

Intervention Type: BIOLOGICAL

Other Intervention Names

Veklury

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

NETWORK

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

Kirby Institute

OTHER_GOV

Sponsor Role: collaborator

Washington D.C. Veterans Affairs Medical Center

FED

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

Prevention and Early Treatment of Acute Lung Injury

OTHER

Sponsor Role: collaborator

Cardiothoracic Surgical Trials Network

OTHER

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jens Lundgren, Prof.

Role: PRINCIPAL_INVESTIGATOR

INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen

James Neaton, Prof.

Role: STUDY_CHAIR

INSIGHT Statistical and Data Management Center, University of Minnesota

Locations

Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304

Chula Vista, California, 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

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

UC Davis Health (Site 203-004), 2315 Stockton Blvd.

Sacramento, California, 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

National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street

Denver, Colorado, 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 D.C., District of Columbia, United States

Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104

Bay Pines, Florida, United States

Hillsborough County Health Department, University of South Florida (Site 032-001)

Tampa, Florida, United States

Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard

Fort Wayne, Indiana, United States

Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway

New Orleans, Louisiana, United States

Massachusetts General Hospital (Site 202-002), 55 Fruit Street

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.

Boston, Massachusetts, United States

Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.

Detroit, Michigan, United States

Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive

Lebanon, New Hampshire, United States

Duke University Hospital (Site 301-006), 2301 Erwin Road

Durham, North Carolina, 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

Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street

Charleston, South Carolina, United States

MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214

Charleston, South Carolina, United States

MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway

Florence, South Carolina, 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

Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.

Dallas, Texas, United States

University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207

Salt Lake City, Utah, United States

West Virginia University (Site 301-023), One Medical Center Drive

Morgantown, West Virginia, United States

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, , Denmark

Countries

United States; Denmark

Provided Documents

Document Type: Study Protocol: Trial H6 Protocol

View Document

Document Type: Study Protocol: Master Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

014/ACTIV-3/H6

Identifier Type: -

Identifier Source: org_study_id