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

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Suspended
CT.gov ID
NCT05780541
Collaborator
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) (Other), University of Copenhagen (Other), Medical Research Council (Other), Kirby Institute (Other), Washington D.C. Veterans Affairs Medical Center (U.S. Fed), AIDS Clinical Trials Group (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), US Department of Veterans Affairs (U.S. Fed), Prevention and Early Treatment of Acute Lung Injury (PETAL) (Other), Cardiothoracic Surgical Trials Network (CTSN) (Other), Pfizer (Industry), University of Minnesota (Other)
58
Enrollment
40
Locations
2
Arms
21.5
Anticipated Duration (Months)
1.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 standard of care (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.

Study Design

Study Type:
Interventional
Actual Enrollment :
58 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Sep 15, 2021
Actual Primary Completion Date :
Apr 6, 2022
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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

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.

Biological: Remdesivir
Antiviral agent
Other Names:
  • Veklury

    		•
    Placebo Comparator: 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

    Drug: Placebo
    Commercially available 0.9% sodium chloride solution

    Biological: Remdesivir
    Antiviral agent
    Other Names:
  • Veklury

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time from randomization to sustained recovery [Up to 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.

    Secondary Outcome Measures

    1. All-cause mortality [Through Day 90]

    2. Composite of time to sustained recovery and mortality [Through Day 90]

    3. Days alive outside short-term acute care hospital [Up to Day 90]

    4. Pulmonary ordinal outcome [Days 1-7, 14 and 28]

      Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    5. Pulmonary+ ordinal outcome [Days 1-7]

      Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    6. Incidence of clinical organ failure [Through Day 28]

    7. Composite of death or serious clinical COVID-19 related events [Through Day 90]

    8. Composite of cardiovascular events and thromboembolic events [Through Day 90]

    9. Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death [Through Days 5 and 28]

    10. Incidence of infusion reactions [Through Day 0]

    11. Composite of SAEs or death [Through 18 months]

    12. Change in SARS-CoV-2 neutralizing antibody levels [Baseline to Days 1, 3, 5, 28 and 90]

    13. Change in overall titers of antibodies [Baseline to Days 1, 3, 5, 28 and 90]

    14. Change in neutralizing antibody levels [Baseline to Days 1, 3, 5, 28 and 90]

    15. Incidence of home use of supplemental oxygen above pre-morbid oxygen use [18 months]

      Measured as: Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14-day period.

    16. Incidence of no home use of supplemental oxygen above pre-morbid oxygen use [14 days]

      Measured as: Alive at home for an uninterrupted 14-day period and no use of continuous supplemental oxygen at end of 14-day time period.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304 Chula Vista California United States 91911
    2 Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd. Los Angeles California United States 90048
    3 Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way Mather California United States 95655
    4 Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive Newport Beach California United States 92663
    5 Palo Alto VAMC (Site 074-005), 3801 Miranda Avenue Palo Alto California United States 94304
    6 UC Davis Health (Site 203-004), 2315 Stockton Blvd. Sacramento California United States 95817
    7 VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive San Diego California United States 92161
    8 San Francisco VAMC (Site 074-002), 4150 Clement St. San Francisco California United States 94121
    9 National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street Denver Colorado United States 80206
    10 West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue West Haven Connecticut United States 06516
    11 MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW. Washington District of Columbia United States 20010
    12 Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104 Bay Pines Florida United States 33744
    13 Hillsborough County Health Department, University of South Florida (Site 032-001) Tampa Florida United States 33602
    14 Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard Fort Wayne Indiana United States 46804
    15 Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway New Orleans Louisiana United States 70121
    16 Massachusetts General Hospital (Site 202-002), 55 Fruit Street Boston Massachusetts United States 02114
    17 Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave. Boston Massachusetts United States 02215
    18 Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd. Detroit Michigan United States 48202
    19 Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive Lebanon New Hampshire United States 03756
    20 Duke University Hospital (Site 301-006), 2301 Erwin Road Durham North Carolina United States 27710
    21 Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road Portland Oregon United States 97239
    22 Rhode Island Hospital (Site 080-036), 593 Eddy Street Providence Rhode Island United States 02903
    23 The Miriam Hospital (Site 080-039), 164 Summit Ave. Providence Rhode Island United States 02906
    24 Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street Charleston South Carolina United States 29401
    25 MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214 Charleston South Carolina United States 29425
    26 MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway Florence South Carolina United States 29505
    27 Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd Dallas Texas United States 75235
    28 UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor Dallas Texas United States 75235
    29 Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave. Dallas Texas United States 75246
    30 University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207 Salt Lake City Utah United States 84108
    31 West Virginia University (Site 301-023), One Medical Center Drive Morgantown West Virginia United States 26506
    32 Aalborg Hospital (Site 625-005), Hobrovej 18 Aalborg Denmark 9000
    33 Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99 Aarhus N Denmark 8200
    34 Righospitalet (Site 625-006), Blegdamsvej 9, Copenhagen Ø Denmark 2100
    35 Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23 Copenhagen Denmark 2400
    36 Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75 Herlev Denmark 2730
    37 Nordsjællands Hospital (Site 625-009), Dyrehavevej 29 Hillerød Denmark 3400
    38 Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24 Kolding Denmark 6000
    39 Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4 Odense Denmark 5000
    40 Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10 Roskilde Denmark 4000

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Jens Lundgren, Prof., INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
    • Study Chair: James Neaton, Prof., INSIGHT Statistical and Coordinating Centre, University of Minnesota

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT05780541
    Other Study ID Numbers:
    • 014/ACTIV-3/H6
    First Posted:
    Mar 22, 2023
    Last Update Posted:
    Mar 24, 2023
    Last Verified:
    Mar 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
    COVID-19
    COVID 19
    Coronaviridae Infections
    Coronavirus Infections
    RNA Virus Infections
    Virus Diseases
    Nidovirales Infections
    SARS-CoV-2
    SARS Coronavirus
    ACTIV-3
    ACTIV3
    TICO
    Additional relevant MeSH terms:
    COVID-19
    Remdesivir

    Study Results

    No Results Posted as of Mar 24, 2023