This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.
This is a master protocol to evaluate the safety and efficacy of multiple investigational
agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly
enhancing viral control in order to limit disease progression.
The protocol is for a randomized, blinded, controlled platform study that allows
investigational drugs to be added and dropped during the course of the study. This allows for
efficient testing of new drugs against placebo and standard of care (SOC) treatment within
the same study. 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. For investigational drugs with minimal
pre-existing safety knowledge, the pace of enrollment with be initially restricted, and there
will be an early review of safety data by the DSMB. For the study of each agent, 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.
Both ordinal outcomes are used to assess futility because it is currently unclear whether the
investigational agents under study will primarily influence non-pulmonary outcomes, for which
risk is increased with SARS-CoV-2 infection, in part, through mechanisms that may be
different from those that influence pulmonary outcomes.
For investigational agents passing this 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.
The international trials within this protocol 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.
Biological: LY3819253
Participants are no longer being randomized to this intervention.
Drug: Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion
Biological: Remdesivir
Provided to all study participants as SOC unless contraindicated for an individual patient.
Biological: VIR-7831
Participants are no longer being randomized to this intervention.
Biological: BRII-196/BRII-198
Participants are no longer being randomized to this intervention.
Biological: AZD7442
Participants are no longer being randomized to this intervention.
Other Name: AZD8895 + AZD1061
Drug: MP0420
Participants are no longer being randomized to this intervention.
Other Name: ensovibep
Drug: PF-07304814
250 mg per day for 5 days. Administered as a constant rate intravenous infusion. Suspended: Participants are not currently being randomized to this intervention.
Inclusion Criteria:
- Signed informed consent.
- Positive test for COVID-19 and progressive disease suggestive of ongoing COVID-19
infection.
- Symptoms of COVID-19 for ≤ 12 days.
- Require admission to hospital for acute medical care (not for purely public health or
quarantine purposes).
Exclusion Criteria:
- Patients who have received plasma from a person who recovered from COVID-19 or who
have received neutralizing monoclonal antibodies at any time prior to hospitalization.
- Patients not willing to abstain from participation in other COVID-19 treatment trials
until after Day 5 of the study. Co-enrollment in certain trials that compare
recommended Standard of Care treatments may be allowed, based on the opinion of the
study leadership team.
- Any condition which, in the opinion of the responsible investigator, participation
would not be in the best interest of the participant or that could prevent, limit, or
confound the protocol-specified assessments.
- Patients considered unable to participate in study procedures.
- Women of child-bearing potential who are not already pregnant at study entry and who
are unwilling to acknowledge strong advice to abstain from sexual intercourse with men
or practice appropriate contraception through 18 months of the study.
- 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 (PF-07304814 investigational agent).
- Pregnant women (PF-07304814 investigational agents).
- Nursing mothers (PF-07304814 investigational agents).
- 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 18 months 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 (PF-07304814 investigational agent).
- Presence at study enrollment of any of the following:
1. stroke
2. meningitis
3. encephalitis
4. myelitis
5. myocardial ischemia
6. myocarditis
7. pericarditis
8. symptomatic congestive heart failure
9. arterial or deep venous thrombosis or pulmonary embolism
- Current or imminent requirement for any of the following:
1. invasive mechanical ventilation
2. ECMO (extracorporeal membrane oxygenation)
3. Mechanical circulatory support
4. vasopressor therapy
5. commencement of renal replacement therapy at this admission (i.e. not patients on
chronic renal replacement therapy).
- Participants with moderate to severe hepatic impairment (i.e. Child-Pugh class B or C)
or acute liver failure (PF-07304814 investigational agent).
- Participants receiving any medications or substances that are strong inhibitors or
inducers of cytochrome P450 (CYP) 3A4 (PF-07304814 investigational agent).
- 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 (PF-07304814 investigational agent).
- Patients with a history of deep vein thrombosis or pulmonary thrombotic embolism
(Prior to initial futility assessment of PF-07304814 investigational agent).
Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
Tucson, Arizona, United States
Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.
Tucson, Arizona, United States
Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304
Chula Vista, California, United States
Community Regional Medical Center (Site 203-005), 2823 Fresno Street
Fresno, California, United States
Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1
La Mesa, California, United States
VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
Loma Linda, California, United States
VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)
Long Beach, California, United States
Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
Los Angeles, California, United States
Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
Los Angeles, California, United States
Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
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
UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
San Francisco, California, United States
San Francisco VAMC (Site 074-002), 4150 Clement St.
San Francisco, California, United States
UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.
San Francisco, California, United States
Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
Stanford, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building
Torrance, California, United States
University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
Aurora, Colorado, United States
Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)
Denver, Colorado, 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 Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW
Washington, District of Columbia, United States
MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.
Washington, District of Columbia, United States
Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW
Washington, 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
Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street
Clearwater, Florida, United States
North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road
Gainesville, Florida, United States
Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street
Hollywood, Florida, United States
Miami VAMC (Site 074-003), 1201 NW 16 Street
Miami, Florida, United States
Hillsborough County Health Department, University of South Florida (Site 032-001)
Tampa, Florida, United States
Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE
Atlanta, Georgia, United States
Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
Fort Wayne, Indiana, United States
Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue
Topeka, Kansas, United States
University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
Lexington, Kentucky, United States
Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
New Orleans, Louisiana, United States
University of Maryland Medical Center (Site 301-019), 22 South Greene Street
Baltimore, Maryland, 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
Baystate Medical Center (Site 201-001), 759 Chestnut Street
Springfield, Massachusetts, United States
University of Michigan (Site 205-001), 1500 East Medical Center Drive
Ann Arbor, Michigan, United States
Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
Detroit, Michigan, United States
Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100
Minneapolis, Minnesota, United States
Hennepin Healthcare (Site 027-001), 701 Park Avenue
Minneapolis, Minnesota, United States
Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70
Minneapolis, Minnesota, United States
M Health Fairview University of Minnesota Medical Center (Site 112-001), 500 Harvard St. SE.
Minneapolis, Minnesota, United States
University of Mississippi Medical Center (Site 202-005), 2500 North State Street
Jackson, Mississippi, United States
VA St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201
Saint Louis, Missouri, United States
Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
Lebanon, New Hampshire, United States
Cooper University Hospital (Site 019-001), One Cooper Plaza
Camden, New Jersey, United States
Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street
Bronx, New York, United States
Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
Bronx, New York, United States
Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
Bronx, New York, United States
SUNY Downstate Medical Center (Site 033-001), 450 Clarkson Ave.
Brooklyn, New York, United States
Maimonides Medical Center (Site 033-002), 4802 10th Avenue
Brooklyn, New York, United States
Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620
New York, New York, United States
Duke University Hospital (Site 301-006), 2301 Erwin Road
Durham, North Carolina, United States
Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center (Site 108-001), 11100 Euclid Avenue
Cleveland, Ohio, United States
Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
Cleveland, Ohio, United States
Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
Cleveland, Ohio, United States
Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
Garfield Heights, Ohio, United States
Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
Portland, Oregon, United States
Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road
Portland, Oregon, United States
UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street
Pittsburgh, Pennsylvania, United States
UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street
Pittsburgh, Pennsylvania, United States
UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue
Pittsburgh, Pennsylvania, 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
VA Providence Healthcare System (Site 074-025), 830 Chalkstone 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
VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South
Nashville, Tennessee, United States
Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
Nashville, Tennessee, United States
Hendrick Medical Center (Site 080-014), 1900 Pine Street
Abilene, Texas, United States
CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street
Corpus Christi, 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
Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
Dallas, Texas, United States
Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street
Houston, Texas, United States
Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
Houston, Texas, United States
Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266
Houston, Texas, United States
CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.
Longview, Texas, United States
Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
Murray, Utah, United States
University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
Salt Lake City, Utah, United States
LDS Hospital (Site 211-004), 8th Ave. C Street
Salt Lake City, Utah, United States
University of Virginia Health Systems (Site 301-021), 1215 Lee Street
Charlottesville, Virginia, United States
Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street
Richmond, Virginia, United States
Carilion Roanoke Memorial Hospital (Site 080-018), 1906 Belleview Avenue
Roanoke, Virginia, United States
Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.
Salem, Virginia, United States
Harborview Medical Center (Site 208-001), 325 9th Avenue
Seattle, Washington, United States
Swedish Hospital First Hill (Site 208-005), 747 Broadway
Seattle, Washington, United States
University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street
Seattle, Washington, 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
Righospitalet (Site 625-006), Blegdamsvej 9,
Copenhagen Ø, Denmark
Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23
Copenhagen, Denmark
Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
Herlev, Denmark
Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
Hillerød, Denmark
Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30
Hvidovre, 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
Democritus University of Thrace (Site 635-021), University General Hospital of Alexandroupolis, Dragana
Alexandroupolis, Evros, Greece
Evangelismos COVID-19 Unit, (Site 635-020), 1st Dept. of Pulmonary and Critical Care Medicine, Evangelismos General Hospital, Dept., Ipsilantou 45-47
Athens, Greece
1st Respiratory Medicine Dept., Athens University Medical School (Site 635-015), Athens Hospital for Diseases of the Chest "Sotiria Hospital", 152 Mesogeion Ave.
Athens, Greece
3rd Dept. of Medicine, Medical School, NKUA (Site 635-022), Sotiria General Hospital, 152 Mesogeion Ave.
Athens, Greece
Attikon University General Hospital (Site 635-009), 4th Dept. of Internal Medicine, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari
Athens, Greece
Institute of Human Virology Nigeria (IHVN) (Site 612-601), Plot 252, Herbert Macaulay Way, Central Business District
Abuja, Nigeria
Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37
Warsaw, Poland
Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng
Singapore, Singapore
Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n
Badalona, Barcelona, Spain
Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80
Lleida, Leida, Spain
Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29
Barcelona, Spain
Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129
Barcelona, Spain
Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170
Barcelona, Spain
Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n
Barcelona, Spain
Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46
Madrid, Spain
Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN
Madrid, Spain
UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal
Madrid, Spain
University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100
Zürich, Zurich, Switzerland
MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital
Entebbe, Uganda
Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160
Gulu, Uganda
Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill
Kampala, Uganda
St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146
Kampala, Uganda
Lira Regional Referral Hospital (Site 634-605)
Lira, Uganda
Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556
Masaka, Uganda
Royal Victoria Infirmary (Site 634-007), Queen Victoria Road
Newcastle Upon Tyne, Northumbria, United Kingdom
Royal Free Hospital (Site 634-006), Pond Street, Hampstead
London, United Kingdom
Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)
London, United Kingdom