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

NCT05780541 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 014/ACTIV-3/H6
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 40

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.

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

Outcome Measures

Primary Outcomes (2)

• 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

• Number of Participants With an Ordinal Outcome on Day 5

  Ordinal outcome with 7 mutually exclusive categories

  Status on Day 5

Secondary Outcomes (4)

• Number of Participants Who Died From All Causes

  Through Day 90

• Number of Participants With a Safety Outcome Through Day 5

  Through Day 5

• Number of Participants With a Safety Outcome Through Day 28

  Through Day 28

• Number of Participants With a Safety Outcome Through Day 90

  Through Day 90

Study Arms (2)

PF-07304814 plus SOC

EXPERIMENTAL

* 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

Drug: PF-07304814; Biological: Remdesivir

Placebo plus SOC

PLACEBO COMPARATOR

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

Drug: Placebo; Biological: Remdesivir

Interventions

PF-07304814 DRUG

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

PF-07304814 plus SOC

Placebo DRUG

Commercially available 0.9% sodium chloride solution

Placebo plus SOC

Remdesivir BIOLOGICAL

Antiviral agent

Also known as: Veklury

PF-07304814 plus SOC; Placebo plus SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• International Network for Strategic Initiatives in Global HIV Trials (INSIGHT): collaborator
• University of Copenhagen: collaborator
• Medical Research Council: collaborator
• Kirby Institute: collaborator
• Washington D.C. Veterans Affairs Medical Center: collaborator
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• US Department of Veterans Affairs: collaborator
• Prevention and Early Treatment of Acute Lung Injury: collaborator
• Cardiothoracic Surgical Trials Network: collaborator
• Pfizer: collaborator
• University of Minnesota: collaborator

Study Sites (40)

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

Chula Vista, California, 91911, United States

Location

Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.

Los Angeles, California, 90048, United States

Location

Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way

Mather, California, 95655, United States

Location

Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive

Newport Beach, California, 92663, United States

Location

Palo Alto VAMC (Site 074-005), 3801 Miranda Avenue

Palo Alto, California, 94304, United States

Location

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

Sacramento, California, 95817, United States

Location

VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive

San Diego, California, 92161, United States

Location

San Francisco VAMC (Site 074-002), 4150 Clement St.

San Francisco, California, 94121, United States

Location

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

Denver, Colorado, 80206, United States

Location

West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue

West Haven, Connecticut, 06516, United States

Location

MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.

Washington D.C., District of Columbia, 20010, United States

Location

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

Bay Pines, Florida, 33744, United States

Location

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

Tampa, Florida, 33602, United States

Location

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

Fort Wayne, Indiana, 46804, United States

Location

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

New Orleans, Louisiana, 70121, United States

Location

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

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02215, United States

Location

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

Detroit, Michigan, 48202, United States

Location

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

Lebanon, New Hampshire, 03756, United States

Location

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

Durham, North Carolina, 27710, United States

Location

Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road

Portland, Oregon, 97239, United States

Location

Rhode Island Hospital (Site 080-036), 593 Eddy Street

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital (Site 080-039), 164 Summit Ave.

Providence, Rhode Island, 02906, United States

Location

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

Charleston, South Carolina, 29401, United States

Location

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

Charleston, South Carolina, 29425, United States

Location

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

Florence, South Carolina, 29505, United States

Location

Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd

Dallas, Texas, 75235, United States

Location

UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor

Dallas, Texas, 75235, United States

Location

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

Dallas, Texas, 75246, United States

Location

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

Salt Lake City, Utah, 84108, United States

Location

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

Morgantown, West Virginia, 26506, United States

Location

Aalborg Hospital (Site 625-005), Hobrovej 18

Aalborg, 9000, Denmark

Location

Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99

Aarhus N, 8200, Denmark

Location

Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23

Copenhagen, 2400, Denmark

Location

Righospitalet (Site 625-006), Blegdamsvej 9,

Copenhagen Ø, 2100, Denmark

Location

Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75

Herlev, 2730, Denmark

Location

Nordsjællands Hospital (Site 625-009), Dyrehavevej 29

Hillerød, 3400, Denmark

Location

Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24

Kolding, 6000, Denmark

Location

Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4

Odense, 5000, Denmark

Location

Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10

Roskilde, 4000, Denmark

Location

MeSH Terms

Conditions

COVID-19; Coronaviridae Infections; Coronavirus Infections; RNA Virus Infections; Virus Diseases; Nidovirales Infections; Severe Acute Respiratory Syndrome

Interventions

lufotrelvir; remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Greg Grandits
• Organization: University of Minnesota

greg-g@ccbr.umn.edu

651-528-9491

Study Officials

• Jens Lundgren, Prof.

  INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen

  PRINCIPAL INVESTIGATOR

• James Neaton, Prof.

  INSIGHT Statistical and Data Management Center, University of Minnesota

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: March 22, 2023
• Study Start: September 15, 2021
• Primary Completion: April 6, 2022
• Study Completion: July 14, 2023
• Last Updated: February 9, 2024
• Results First Posted: February 9, 2024

Record last verified: 2024-02

Locations

US (31); DK (9)