- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04501978
ACTIV-3: Therapeutics for Inpatients With COVID-19 (TICO)
A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19
Study Overview
Status
Conditions
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Aalborg, Denmark, 9000
- Aalborg Hospital (Site 625-005), Hobrovej 18
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Aarhus N, Denmark, 8200
- Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
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Copenhagen, Denmark, 2400
- Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23
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Copenhagen Ø, Denmark, 2100
- Righospitalet (Site 625-006), Blegdamsvej 9,
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Herlev, Denmark, 2730
- Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
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Hillerød, Denmark, 3400
- Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
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Hvidovre, Denmark, 2650
- Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30
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Kolding, Denmark, 6000
- Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
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Odense, Denmark, 5000
- Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
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Roskilde, Denmark, 4000
- Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10
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Athens, Greece, 106 76
- Evangelismos COVID-19 Unit, (Site 635-020), 1st Dept. of Pulmonary and Critical Care Medicine, Evangelismos General Hospital, Dept., Ipsilantou 45-47
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Athens, Greece, 115 27
- 1st Respiratory Medicine Dept., Athens University Medical School (Site 635-015), Athens Hospital for Diseases of the Chest "Sotiria Hospital", 152 Mesogeion Ave.
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Athens, Greece, 115 27
- 3rd Dept. of Medicine, Medical School, NKUA (Site 635-022), Sotiria General Hospital, 152 Mesogeion Ave.
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Athens, Greece, 124 62
- Attikon University General Hospital (Site 635-009), 4th Dept. of Internal Medicine, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari
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Evros
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Alexandroupolis, Evros, Greece, 68131
- Democritus University of Thrace (Site 635-021), University General Hospital of Alexandroupolis, Dragana
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Abuja, Nigeria
- Institute of Human Virology Nigeria (IHVN) (Site 612-601), Plot 252, Herbert Macaulay Way, Central Business District
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Warsaw, Poland, 01-201
- Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37
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Singapore, Singapore, 308433
- Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng
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Barcelona, Spain, 08003
- Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29
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Barcelona, Spain, 08035
- Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129
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Barcelona, Spain, 08036
- Hospital Clinic de Barcelona (Site 626-004), Carrer de Villaroel 170
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Barcelona, Spain, 08907
- Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n
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Madrid, Spain, 28017
- Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46
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Madrid, Spain, 28040
- Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN
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Madrid, Spain, 28046
- UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal
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Barcelona
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Badalona, Barcelona, Spain, 08916
- Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n
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Leida
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Lleida, Leida, Spain, 25198
- Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80
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Zurich
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Zürich, Zurich, Switzerland, 8091
- University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100
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Entebbe, Uganda
- MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital
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Gulu, Uganda
- Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160
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Kampala, Uganda
- Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill
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Kampala, Uganda
- St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146
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Lira, Uganda
- Lira Regional Referral Hospital (Site 634-605)
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Masaka, Uganda
- Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556
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London, United Kingdom, NW3 2QG
- Royal Free Hospital (Site 634-006), Pond Street, Hampstead
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London, United Kingdom, SE1 7EH
- Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)
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Northumbria
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Newcastle Upon Tyne, Northumbria, United Kingdom, NE1 4LP
- Royal Victoria Infirmary (Site 634-007), Queen Victoria Road
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Arizona
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Tucson, Arizona, United States, 85719
- Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
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Tucson, Arizona, United States, 85723
- Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.
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California
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Chula Vista, California, United States, 91911
- Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304
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Fresno, California, United States, 93701
- Community Regional Medical Center (Site 203-005), 2823 Fresno Street
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La Mesa, California, United States, 91942
- Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1
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Loma Linda, California, United States, 92357
- VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
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Long Beach, California, United States, 90822
- VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)
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Los Angeles, California, United States, 90033
- Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
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Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
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Los Angeles, California, United States, 90095
- Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
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Mather, California, United States, 95655
- Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way
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Newport Beach, California, United States, 92663
- Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive
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Palo Alto, California, United States, 94304
- Palo Alto VAMC (Site 074-005), 3801 Miranda Avenue
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Sacramento, California, United States, 95817
- UC Davis Health (Site 203-004), 2315 Stockton Blvd.
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San Diego, California, United States, 92161
- VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive
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San Francisco, California, United States, 94115
- UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
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San Francisco, California, United States, 94121
- San Francisco VAMC (Site 074-002), 4150 Clement St.
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San Francisco, California, United States, 94143
- UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.
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Stanford, California, United States, 94305
- Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
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Torrance, California, United States, 90502
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
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Denver, Colorado, United States, 80204
- Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)
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Denver, Colorado, United States, 80206
- National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street
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Connecticut
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West Haven, Connecticut, United States, 06516
- West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue
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District of Columbia
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Washington, District of Columbia, United States, 20007
- MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW
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Washington, District of Columbia, United States, 20010
- MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.
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Washington, District of Columbia, United States, 20422
- Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW
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Florida
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Bay Pines, Florida, United States, 33744
- Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104
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Clearwater, Florida, United States, 33756
- Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street
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Gainesville, Florida, United States, 32608-1197
- North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road
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Hollywood, Florida, United States, 33021
- Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street
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Miami, Florida, United States, 33125
- Miami VAMC (Site 074-003), 1201 NW 16 Street
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Tampa, Florida, United States, 33602
- Hillsborough County Health Department, University of South Florida (Site 032-001)
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE
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Indiana
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Fort Wayne, Indiana, United States, 46804
- Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
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Kansas
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Topeka, Kansas, United States, 66604
- Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
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Maryland
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Baltimore, Maryland, United States, 21201
- University of Maryland Medical Center (Site 301-019), 22 South Greene Street
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital (Site 202-002), 55 Fruit Street
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.
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Springfield, Massachusetts, United States, 01199
- Baystate Medical Center (Site 201-001), 759 Chestnut Street
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan (Site 205-001), 1500 East Medical Center Drive
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Detroit, Michigan, United States, 48202
- Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
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Minnesota
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Minneapolis, Minnesota, United States, 55407
- Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100
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Minneapolis, Minnesota, United States, 55415
- Hennepin Healthcare (Site 027-001), 701 Park Avenue
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Minneapolis, Minnesota, United States, 55417
- Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70
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Minneapolis, Minnesota, United States, 55455
- M Health Fairview University of Minnesota Medical Center (Site 112-001), 500 Harvard St. SE.
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Mississippi
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Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center (Site 202-005), 2500 North State Street
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Missouri
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Saint Louis, Missouri, United States, 63106
- VA St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
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New Jersey
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Camden, New Jersey, United States, 08103
- Cooper University Hospital (Site 019-001), One Cooper Plaza
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New York
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Bronx, New York, United States, 10451
- Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street
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Bronx, New York, United States, 10461
- Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
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Bronx, New York, United States, 10467
- Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
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Brooklyn, New York, United States, 11203
- SUNY Downstate Medical Center (Site 033-001), 450 Clarkson Ave.
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Brooklyn, New York, United States, 11219
- Maimonides Medical Center (Site 033-002), 4802 10th Avenue
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New York, New York, United States, 10029
- Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Hospital (Site 301-006), 2301 Erwin Road
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
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Ohio
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Cincinnati, Ohio, United States, 45219
- University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.
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Cleveland, Ohio, United States, 44106
- University Hospitals Cleveland Medical Center (Site 108-001), 11100 Euclid Avenue
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Cleveland, Ohio, United States, 44111
- Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
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Garfield Heights, Ohio, United States, 44125
- Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
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Oregon
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Portland, Oregon, United States, 97239-3098
- Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
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Portland, Oregon, United States, 97239
- Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street
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Pittsburgh, Pennsylvania, United States, 15213
- UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue
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Rhode Island
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Providence, Rhode Island, United States, 02903
- Rhode Island Hospital (Site 080-036), 593 Eddy Street
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Providence, Rhode Island, United States, 02906
- The Miriam Hospital (Site 080-039), 164 Summit Ave.
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Providence, Rhode Island, United States, 02908
- VA Providence Healthcare System (Site 074-025), 830 Chalkstone Ave.
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South Carolina
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Charleston, South Carolina, United States, 29401
- Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street
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Charleston, South Carolina, United States, 29425
- MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214
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Florence, South Carolina, United States, 29505
- MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway
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Tennessee
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Nashville, Tennessee, United States, 37212
- VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
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Texas
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Abilene, Texas, United States, 79601
- Hendrick Medical Center (Site 080-014), 1900 Pine Street
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Corpus Christi, Texas, United States, 78404
- CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street
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Dallas, Texas, United States, 75235
- Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd
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Dallas, Texas, United States, 75235
- UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
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Dallas, Texas, United States, 75246
- Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
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Houston, Texas, United States, 77030
- Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street
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Houston, Texas, United States, 77030
- Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
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Houston, Texas, United States, 77030
- Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266
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Longview, Texas, United States, 75601
- CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.
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Utah
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Murray, Utah, United States, 84107
- Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
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Salt Lake City, Utah, United States, 84108
- University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
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Salt Lake City, Utah, United States, 84143
- LDS Hospital (Site 211-004), 8th Ave. C Street
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Virginia
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Charlottesville, Virginia, United States, 22903
- University of Virginia Health Systems (Site 301-021), 1215 Lee Street
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street
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Roanoke, Virginia, United States, 24014
- Carilion Roanoke Memorial Hospital (Site 080-018), 1906 Belleview Avenue
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Salem, Virginia, United States, 24153
- Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.
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Washington
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Seattle, Washington, United States, 98104
- Harborview Medical Center (Site 208-001), 325 9th Avenue
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Seattle, Washington, United States, 98122
- Swedish Hospital First Hill (Site 208-005), 747 Broadway
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Seattle, Washington, United States, 98195
- University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street
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West Virginia
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Morgantown, West Virginia, United States, 26506
- West Virginia University (Site 301-023), One Medical Center Drive
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
- stroke
- meningitis
- encephalitis
- myelitis
- myocardial ischemia
- myocarditis
- pericarditis
- symptomatic congestive heart failure
- arterial or deep venous thrombosis or pulmonary embolism
Current or imminent requirement for any of the following:
- invasive mechanical ventilation
- ECMO (extracorporeal membrane oxygenation)
- Mechanical circulatory support
- vasopressor therapy
- 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ACTIV-3 Drug plus SOC
Participants in this study will be randomized to receive one of the ACTIV-3 drug treatments plus Standard of Care (SOC) or placebo plus SOC
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Participants are no longer being randomized to this intervention.
Provided to all study participants as SOC unless contraindicated for an individual patient.
Participants are no longer being randomized to this intervention.
Participants are no longer being randomized to this intervention.
Participants are no longer being randomized to this intervention.
Other Names:
Participants are no longer being randomized to this intervention.
Other Names:
250 mg per day for 5 days.
Administered as a constant rate intravenous infusion.
Suspended: Participants are not currently being randomized to this intervention.
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Placebo Comparator: Placebo plus SOC
The placebo arm may be pooled across more than one experimental arm if multiple investigational drugs are available to be tested at the same time.
If it is not possible to use matching placebo over more than one experimental arm, additional placebo arms will be included in the study
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Provided to all study participants as SOC unless contraindicated for an individual patient.
Commercially available 0.9% sodium chloride solution.
Administered by IV infusion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time from randomization to sustained recovery
Time Frame: Up to Day 90
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Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
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Up to Day 90
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
All-cause mortality
Time Frame: Thru Day 90
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Thru Day 90
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Composite of time to sustained recovery and mortality
Time Frame: Thru Day 90
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Thru Day 90
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Days alive outside short-term acute care hospital
Time Frame: Up to Day 90
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Up to Day 90
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Pulmonary ordinal outcome
Time Frame: Days 1-7, 14 and 28
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Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe).
The participant's highest (i.e.
most severe) observed score is used.
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Days 1-7, 14 and 28
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Pulmonary+ ordinal outcome
Time Frame: Days 1-7
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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.
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Days 1-7
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Incidence of clinical organ failure
Time Frame: Thru Day 28
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Thru Day 28
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Composite of death or serious clinical COVID-19 related events
Time Frame: Thru Day 90
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Thru Day 90
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Composite of cardiovascular events and thromboembolic events
Time Frame: Thru Day 90
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Thru Day 90
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Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death
Time Frame: Thru Days 5 and 28
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Thru Days 5 and 28
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Incidence of infusion reactions
Time Frame: Thru Day 0
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Thru Day 0
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Composite of SAEs or death
Time Frame: Thru 18 months
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Thru 18 months
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Change in SARS-CoV-2 neutralizing antibody levels
Time Frame: Baseline to Days 1, 3, 5, 28 and 90
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Baseline to Days 1, 3, 5, 28 and 90
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Change in overall titers of antibodies
Time Frame: Baseline to Days 1, 3, 5, 28 and 90
|
Baseline to Days 1, 3, 5, 28 and 90
|
|
Change in neutralizing antibody levels
Time Frame: Baseline to Days 1, 3, 5, 28 and 90
|
Baseline to Days 1, 3, 5, 28 and 90
|
|
Incidence of home use of supplemental oxygen above pre-morbid oxygen use
Time Frame: 18 months
|
Measured as: Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14 day period
|
18 months
|
Incidence of no home use of supplemental oxygen above pre-morbid oxygen use
Time Frame: 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.
|
14 days
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Prof. Jens Lundgren, INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
- Study Chair: Prof. James Neaton, INSIGHT Statistical and Coordinating Centre, University of Minnesota
Publications and helpful links
General Publications
- Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- ACTIV-3-Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022 Oct;10(10):972-984. doi: 10.1016/S2213-2600(22)00215-6. Epub 2022 Jul 8. Erratum In: Lancet Respir Med. 2022 Nov 7;:
- Wick KD, Siegel L, Neaton JD, Oldmixon C, Lundgren J, Dewar RL, Lane HC, Thompson BT, Matthay MA; ACTIV-3/TICO study group. RAGE has potential pathogenetic and prognostic value in nonintubated hospitalized patients with COVID-19. JCI Insight. 2022 May 9;7(9):e157499. doi: 10.1172/jci.insight.157499.
- ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infect Dis. 2022 May;22(5):622-635. doi: 10.1016/S1473-3099(21)00751-9. Epub 2021 Dec 23.
- Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
- ACTIV-3/TICO Study Group; Barkauskas C, Mylonakis E, Poulakou G, Young BE, Vock DM, Siegel L, Engen N, Grandits G, Mosaly NR, Vekstein AM, Rogers R, Shehadeh F, Kaczynski M, Mylona EK, Syrigos KN, Rapti V, Lye DC, Hui DS, Leither L, Knowlton KU, Jain MK, Marines-Price R, Osuji A, Overcash JS, Kalomenidis I, Barmparessou Z, Waters M, Zepeda K, Chen P, Torbati S, Kiweewa F, Sebudde N, Almasri E, Hughes A, Bhagani SR, Rodger A, Sandkovsky U, Gottlieb RL, Nnakelu E, Trautner B, Menon V, Lutaakome J, Matthay M, Robinson P, Protopapas K, Koulouris N, Kimuli I, Baduashvili A, Braun DL, Gunthard HF, Ramachandruni S, Kidega R, Kim K, Hatlen TJ, Phillips AN, Murray DD, Jensen TO, Padilla ML, Accardi EX, Shaw-Saliba K, Dewar RL, Teitelbaum M, Natarajan V, Laverdure S, Highbarger HC, Rehman MT, Vogel S, Vallee D, Crew P, Atri N, Schechner AJ, Pett S, Hudson F, Badrock J, Touloumi G, Brown SM, Self WH, North CM, Ginde AA, Chang CC, Kelleher A, Nagy-Agren S, Vasudeva S, Looney D, Nguyen HH, Sanchez A, Weintrob AC, Grund B, Sharma S, Reilly CS, Paredes R, Bednarska A, Gerry NP, Babiker AG, Davey VJ, Gelijns AC, Higgs ES, Kan V, Matthews G, Thompson BT, Legenne P, Chandra R, Lane HC, Neaton JD, Lundgren JD. Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial. Ann Intern Med. 2022 Sep;175(9):1266-1274. doi: 10.7326/M22-1503. Epub 2022 Aug 9.
- ACTIV-3/TICO Bamlanivimab Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Ostergaard L, Chang CC, Goodman AL, Chang W, Dewar RL, Gerry NP, Higgs ES, Highbarger H, Murray DD, Murray TA, Natarajan V, Paredes R, Parmar MKB, Phillips AN, Reilly C, Rupert AW, Sharma S, Shaw-Saliba K, Sherman BT, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Davey VJ, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD. Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial. Ann Intern Med. 2022 Feb;175(2):234-243. doi: 10.7326/M21-3507. Epub 2021 Dec 21.
- ACTIV-3/TICO LY-CoV555 Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Ostergaard L, Chang CC, Davey VJ, Goodman A, Higgs ES, Murray DD, Murray TA, Paredes R, Parmar MKB, Phillips AN, Reilly C, Sharma S, Dewar RL, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD. A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. N Engl J Med. 2021 Mar 11;384(10):905-914. doi: 10.1056/NEJMoa2033130. Epub 2020 Dec 22.
Helpful Links
- FDA Safety Alerts and Recalls
- CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
- A Participant's Guide to Clinical Trials (NIAID)
- Find a Clinical Trial (NIAID)
- Clinical Trials at NIAID
- National Institute for Allergy and Infectious Diseases (NIAID)
- NIH COVID-19 treatment guidelines
- WHO COVID-19 treatment guidelines
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- COVID-19
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Remdesivir
- Bamlanivimab
- Cilgavimab and tixagevimab drug combination
- Sotrovimab
Other Study ID Numbers
- 014 / ACTIV-3
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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