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COVID-19Phase 3NCT05780541

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

A Phase 3 study testing PF-07304814 and Remdesivir in people with COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 40 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19
What is being tested?
PF-07304814 and Remdesivir
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
40 sitesin 2 countries
Study dates
15 Sep 2021to 14 Jul 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

40 sites in 2 countries.

40 sites in 2 countries

United States31 sites

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

    Bay Pines, Florida, 33744

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

    Boston, Massachusetts, 02114

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

    Boston, Massachusetts, 02215

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

    Charleston, South Carolina, 29401

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

    Charleston, South Carolina, 29425

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

    Chula Vista, California, 91911

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

    Dallas, Texas, 75235

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

    Dallas, Texas, 75235

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

    Dallas, Texas, 75246

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

    Denver, Colorado, 80206

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

    Detroit, Michigan, 48202

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

    Durham, North Carolina, 27710

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

    Florence, South Carolina, 29505

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

    Fort Wayne, Indiana, 46804

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

    Lebanon, New Hampshire, 03756

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

    Los Angeles, California, 90048

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

    Mather, California, 95655

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

    Morgantown, West Virginia, 26506

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

    New Orleans, Louisiana, 70121

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

    Newport Beach, California, 92663

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

    Palo Alto, California, 94304

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

    Portland, Oregon, 97239

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

    Providence, Rhode Island, 02903

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

    Providence, Rhode Island, 02906

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

    Sacramento, California, 95817

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

    Salt Lake City, Utah, 84108

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

    San Diego, California, 92161

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

    San Francisco, California, 94121

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

    Tampa, Florida, 33602

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

    Washington D.C., District of Columbia, 20010

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

    West Haven, Connecticut, 06516

Other trials in United States

Denmark9 sites

  • Aalborg Hospital (Site 625-005), Hobrovej 18

    Aalborg, 9000

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

    Aarhus N, 8200

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

    Copenhagen, 2400

  • Righospitalet (Site 625-006), Blegdamsvej 9,

    Copenhagen Ø, 2100

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

    Herlev, 2730

  • Nordsjællands Hospital (Site 625-009), Dyrehavevej 29

    Hillerød, 3400

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

    Kolding, 6000

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

    Odense, 5000

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

    Roskilde, 4000

Other trials in Denmark

About this study

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)

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.

Read the 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
Being tested
PF-07304814, Placebo, Remdesivir
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
Medical subject headings
COVID-19, Coronaviridae Infections, Coronavirus Infections, RNA Virus Infections, Virus Diseases, Nidovirales Infections, Severe Acute Respiratory Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-07304814Drug

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

  • PlaceboDrug

    Commercially available 0.9% sodium chloride solution

  • RemdesivirBiological

    Also called Veklury

    Antiviral agent

Study groups in NCT05780541
Study groupRoleWhat they receive
PF-07304814 plus SOCExperimental* 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
Receives: Drug: PF-07304814; Biological: Remdesivir
Placebo plus SOCPlacebo 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
Receives: Drug: Placebo; Biological: Remdesivir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Through Day 90

  2. Number of Participants With an Ordinal Outcome on Day 5

    Ordinal outcome with 7 mutually exclusive categories

    Measured: Status on Day 5

Secondary outcomes (4)

  1. Number of Participants Who Died From All Causes

    All-cause mortality

    Measured: Through Day 90

  2. 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

    Measured: Through Day 5

  3. 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

    Measured: Through Day 28

  4. Number of Participants With a Safety Outcome Through Day 90

    Death, SAE, clinical organ failure, serious infections through Day 90

    Measured: Through Day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2023
  2. Study start15 Sep 2021
  3. Primary completion6 Apr 2022
  4. Study completion14 Jul 2023

Why it stopped: The agent was withdrawn from development by the manufacturer after being placed on clinical hold by the US FDA.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05780541
Sponsor's protocol ID
014/ACTIV-3/H6
Status last verified
Feb 2024
First submitted
20 Mar 2023
Last updated
9 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PF-07304814 and Remdesivir in people with COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 40 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Sustained Recovery (time frame: Through Day 90). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05780541.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2024.

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