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AzTrials

Covid19Phase 3TICONCT04501978

ACTIV-3: Therapeutics for Inpatients With COVID-19

A Phase 3 study testing LY3819253, Remdesivir and VIR-7831 in people with Covid19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 135 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
LY3819253, Remdesivir and VIR-7831
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
2,753 participants
Where
135 sitesin 10 countries
Study dates
4 Aug 2020to 14 Jul 2023
Phase
Phase 3
Are there results?
None posted in the registry

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

Who may be able to join

  • 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).

Who cannot join

  • 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).
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  • 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).

Trial locations and contacts

135 sites in 10 countries.

135 sites in 10 countries

United States98 sites

  • Hendrick Medical Center (Site 080-014), 1900 Pine Street

    Abilene, Texas, 79601

  • University of Michigan (Site 205-001), 1500 East Medical Center Drive

    Ann Arbor, Michigan, 48109

  • Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE

    Atlanta, Georgia, 30322

  • University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue

    Aurora, Colorado, 80045

  • University of Maryland Medical Center (Site 301-019), 22 South Greene Street

    Baltimore, Maryland, 21201

  • 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

  • SUNY Downstate Medical Center (Site 033-001), 450 Clarkson Ave.

    Brooklyn, New York, 11203

  • Maimonides Medical Center (Site 033-002), 4802 10th Avenue

    Brooklyn, New York, 11219

  • Cooper University Hospital (Site 019-001), One Cooper Plaza

    Camden, New Jersey, 08103

  • 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

  • University of Virginia Health Systems (Site 301-021), 1215 Lee Street

    Charlottesville, Virginia, 22903

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

    Chula Vista, California, 91911

  • University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.

    Cincinnati, Ohio, 45219

  • Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street

    Clearwater, Florida, 33756

  • University Hospitals Cleveland Medical Center (Site 108-001), 11100 Euclid Avenue

    Cleveland, Ohio, 44106

  • Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue

    Cleveland, Ohio, 44195

  • CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street

    Corpus Christi, Texas, 78404

  • 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

  • Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)

    Denver, Colorado, 80204

  • 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

  • Community Regional Medical Center (Site 203-005), 2823 Fresno Street

    Fresno, California, 93701

  • North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road

    Gainesville, Florida, 32608-1197

  • Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road

    Garfield Heights, Ohio, 44125

  • Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street

    Hollywood, Florida, 33021

  • Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street

    Houston, Texas, 77030

  • Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.

    Houston, Texas, 77030

  • Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266

    Houston, Texas, 77030

  • University of Mississippi Medical Center (Site 202-005), 2500 North State Street

    Jackson, Mississippi, 39216

  • Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1

    La Mesa, California, 91942

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

    Lebanon, New Hampshire, 03756

  • University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.

    Lexington, Kentucky, 40536

  • VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street

    Loma Linda, California, 92357

  • VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)

    Long Beach, California, 90822

  • CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.

    Longview, Texas, 75601

  • Keck Hospital of USC (Site 301-020), 1500 San Pablo Street

    Los Angeles, California, 90033

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

    Los Angeles, California, 90048

  • Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza

    Los Angeles, California, 90095

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

    Mather, California, 95655

  • Miami VAMC (Site 074-003), 1201 NW 16 Street

    Miami, Florida, 33125

  • Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100

    Minneapolis, Minnesota, 55407

  • Hennepin Healthcare (Site 027-001), 701 Park Avenue

    Minneapolis, Minnesota, 55415

  • Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70

    Minneapolis, Minnesota, 55417

  • M Health Fairview University of Minnesota Medical Center (Site 112-001), 500 Harvard St. SE.

    Minneapolis, Minnesota, 55455

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

    Morgantown, West Virginia, 26506

  • Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street

    Murray, Utah, 84107

  • VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South

    Nashville, Tennessee, 37212

  • Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive

    Nashville, Tennessee, 37232

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

    New Orleans, Louisiana, 70121

  • Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620

    New York, New York, 10029

  • 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

  • UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street

    Pittsburgh, Pennsylvania, 15213

  • UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street

    Pittsburgh, Pennsylvania, 15213

  • UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.

    Portland, Oregon, 97239-3098

  • 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

  • VA Providence Healthcare System (Site 074-025), 830 Chalkstone Ave.

    Providence, Rhode Island, 02908

  • Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street

    Richmond, Virginia, 23298

  • Carilion Roanoke Memorial Hospital (Site 080-018), 1906 Belleview Avenue

    Roanoke, Virginia, 24014

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

    Sacramento, California, 95817

  • Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.

    Salem, Virginia, 24153

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

    Salt Lake City, Utah, 84108

  • LDS Hospital (Site 211-004), 8th Ave. C Street

    Salt Lake City, Utah, 84143

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

    San Diego, California, 92161

  • UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.

    San Francisco, California, 94115

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

    San Francisco, California, 94121

  • UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.

    San Francisco, California, 94143

  • Harborview Medical Center (Site 208-001), 325 9th Avenue

    Seattle, Washington, 98104

  • Swedish Hospital First Hill (Site 208-005), 747 Broadway

    Seattle, Washington, 98122

  • University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street

    Seattle, Washington, 98195

  • Baystate Medical Center (Site 201-001), 759 Chestnut Street

    Springfield, Massachusetts, 01199

  • VA St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201

    St Louis, Missouri, 63106

  • Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.

    Stanford, California, 94305

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

    Tampa, Florida, 33602

  • Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street

    The Bronx, New York, 10451

  • Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road

    The Bronx, New York, 10461

  • Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street

    The Bronx, New York, 10467

  • Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue

    Topeka, Kansas, 66604

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building

    Torrance, California, 90502

  • Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue

    Tucson, Arizona, 85719

  • Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.

    Tucson, Arizona, 85723

  • MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW

    Washington D.C., District of Columbia, 20007

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

    Washington D.C., District of Columbia, 20010

  • Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW

    Washington D.C., District of Columbia, 20422

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

    West Haven, Connecticut, 06516

  • Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd

    Winston-Salem, North Carolina, 27157

Other trials in United States

Denmark10 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

  • Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30

    Hvidovre, 2650

  • 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

Spain9 sites

  • Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n

    Badalona, Barcelona, 08916

  • Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29

    Barcelona, 08003

  • Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129

    Barcelona, 08035

  • Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170

    Barcelona, 08036

  • Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n

    Barcelona, 08907

  • Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80

    Lleida, Leida, 25198

  • Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46

    Madrid, 28017

  • Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN

    Madrid, 28040

  • UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal

    Madrid, 28046

Other trials in Spain

Uganda6 sites

  • MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital

    Entebbe

  • Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160

    Gulu

  • Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill

    Kampala

  • St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146

    Kampala

  • Lira Regional Referral Hospital (Site 634-605)

    Lira

  • Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556

    Masaka

Other trials in Uganda

Greece5 sites

  • Democritus University of Thrace (Site 635-021), University General Hospital of Alexandroupolis, Dragana

    Alexandroupoli, Evros, 68131

  • Evangelismos COVID-19 Unit, (Site 635-020), 1st Dept. of Pulmonary and Critical Care Medicine, Evangelismos General Hospital, Dept., Ipsilantou 45-47

    Athens, 106 76

  • 1st Respiratory Medicine Dept., Athens University Medical School (Site 635-015), Athens Hospital for Diseases of the Chest "Sotiria Hospital", 152 Mesogeion Ave.

    Athens, 115 27

  • 3rd Dept. of Medicine, Medical School, NKUA (Site 635-022), Sotiria General Hospital, 152 Mesogeion Ave.

    Athens, 115 27

  • 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, 124 62

Other trials in Greece

United Kingdom3 sites

  • Royal Free Hospital (Site 634-006), Pond Street, Hampstead

    London, NW3 2QG

  • Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)

    London, SE1 7EH

  • Royal Victoria Infirmary (Site 634-007), Queen Victoria Road

    Newcastle upon Tyne, Northumbria, NE1 4LP

Other trials in United Kingdom

Nigeria1 site

  • Institute of Human Virology Nigeria (IHVN) (Site 612-601), Plot 252, Herbert Macaulay Way, Central Business District

    Abuja

Other trials in Nigeria

Poland1 site

  • Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37

    Warsaw, 01-201

Other trials in Poland

Singapore1 site

  • Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng

    Singapore, 308433

Other trials in Singapore

Switzerland1 site

  • University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100

    Zurich, Canton of Zurich, 8091

Other trials in Switzerland

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

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.

Read the 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.

Conditions
Covid19
Being tested
LY3819253, Placebo, Remdesivir, VIR-7831, BRII-196/BRII-198
Keywords
COVID-19, COVID 19, Coronaviridae Infections, Coronavirus Infections, RNA Virus Infections, Virus Diseases, Nidovirales Infections, SARS-CoV-2, SARS Coronavirus, ACTIV-3, ACTIV3
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.

  • LY3819253Biological

    Participants are no longer being randomized to this intervention.

  • PlaceboDrug

    Commercially available 0.9% sodium chloride solution. Administered by IV infusion

  • RemdesivirBiological

    Provided to all study participants as SOC unless contraindicated for an individual patient.

  • VIR-7831Biological

    Participants are no longer being randomized to this intervention.

  • BRII-196/BRII-198Biological

    Participants are no longer being randomized to this intervention.

  • AZD7442Biological

    Also called AZD8895 + AZD1061

    Participants are no longer being randomized to this intervention.

  • MP0420Drug

    Also called ensovibep

    Participants are no longer being randomized to this intervention.

  • PF-07304814Drug

    250 mg per day for 5 days. Administered as a constant rate intravenous infusion. Suspended: Participants are not currently being randomized to this intervention.

Study groups in NCT04501978
Study groupRoleWhat they receive
ACTIV-3 Drug plus SOCExperimentalParticipants in this study will be randomized to receive one of the ACTIV-3 drug treatments plus Standard of Care (SOC) or placebo plus SOC
Receives: Biological: LY3819253; Biological: Remdesivir; Biological: VIR-7831; Biological: BRII-196/BRII-198; Biological: AZD7442; Drug: MP0420; Drug: PF-07304814
Placebo plus SOCPlacebo comparatorThe 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
Receives: Drug: Placebo; Biological: Remdesivir

What is being measured

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

  1. Time from randomization to 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: Up to Day 90

Secondary outcomes (16)

  1. All-cause mortality

    Measured: Thru Day 90

  2. Composite of time to sustained recovery and mortality

    Measured: Thru Day 90

  3. Days alive outside short-term acute care hospital

    Measured: Up to Day 90

  4. Pulmonary ordinal outcome

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

    Measured: Days 1-7, 14 and 28

  5. Pulmonary+ ordinal outcome

    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.

    Measured: Days 1-7

  6. Incidence of clinical organ failure

    Measured: Thru Day 28

  7. Composite of death or serious clinical COVID-19 related events

    Measured: Thru Day 90

  8. Composite of cardiovascular events and thromboembolic events

    Measured: Thru Day 90

  9. Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death

    Measured: Thru Days 5 and 28

  10. Incidence of infusion reactions

    Measured: Thru Day 0

  11. Composite of SAEs or death

    Measured: Thru 18 months

  12. Change in SARS-CoV-2 neutralizing antibody levels

    Measured: Baseline to Days 1, 3, 5, 28 and 90

  13. Change in overall titers of antibodies

    Measured: Baseline to Days 1, 3, 5, 28 and 90

  14. Change in neutralizing antibody levels

    Measured: Baseline to Days 1, 3, 5, 28 and 90

  15. Incidence of home use of supplemental oxygen above pre-morbid oxygen use

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

    Measured: 18 months

  16. Incidence of no home use of supplemental oxygen above pre-morbid oxygen use

    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.

    Measured: 14 days

Timeline

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

  1. First posted6 Aug 2020
  2. Study start4 Aug 2020
  3. Primary completion6 Apr 2022
  4. Study completion14 Jul 2023

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
2,753 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04501978
Sponsor's protocol ID
014 / ACTIV-3
Acronym
TICO
Status last verified
Aug 2023
First submitted
3 Aug 2020
Last updated
25 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Slotkin R, Kyriakides TC, Yu V, Chen X, Kundu A, Gupta S. CoVimmune COVID-19 Immunity Calculator: Web Application Development and Validation Study. JMIR Form Res. 2025 Apr 22;9:e59467. doi: 10.2196/59467.

    PubMed 40262279

  • Mourad A, Grandits GA, Siegel LK, Engen N, Barkauskas C, Eriobu N, Jain MK, Jensen TO, Ginde A, Higgs E, Knox DB, Kitonsa J, Kim K, Malin JJ, Rapti V, Price DA, Mena Lora AJ, Mathews G, Mylonakis E, Murray TA, Sandkovsky U, Paredes R, Ramachandruni S, Reilly C, Vock D, Williamson JC, Young BE, Self WH, Lundgren J, Holland TL; INSIGHT ACTIV-3/TICO Study Group and the STRIVE Network. Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial. Clin Microbiol Infect. 2025 Jun;31(6):1053-1060. doi: 10.1016/j.cmi.2025.02.002. Epub 2025 Feb 6.

    PubMed 39922466

  • Jensen TO, Grandits GA, Jain MK, Murray TA, Grund B, Shaw-Saliba K, Matthay MA, Abassi M, Ardelt M, Baker JV, Chen P, Dewar RL, Goodman AL, Hatlen TJ, Highbarger HC, Holodniy M, Lallemand P, Laverdure S, Leshnower BG, Looney D, Moschopoulos CD, Mugerwa H, Murray DD, Mylonakis E, Nagy-Agren S, Rehman MT, Rupert A, Stevens RA, Turville S, Weintrob A, Wick K, Lundgren J, Ko ER; ACTIV-3/TICO Study Group. Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19. J Infect Dis. 2024 Mar 14;229(3):671-679. doi: 10.1093/infdis/jiad446.

    PubMed 37948759

  • 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.

    PubMed 35939810

  • 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.

    PubMed 35817072

  • 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.

    PubMed 35713300

  • 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.

    PubMed 35298440

  • 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.

    PubMed 34953520

  • 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.

    PubMed 34928698

  • 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.

    PubMed 34473343

  • 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.

    PubMed 33356051

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LY3819253, Remdesivir and VIR-7831 in people with Covid19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 135 sites in 10 countries.

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

Who may be eligible to take part?

The sponsor lists 4 inclusion and 30 exclusion criteria. 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: finished, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 135 sites in United States, Denmark, Spain, Uganda, Greece and 5 more countries. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Time from randomization to sustained recovery (time frame: Up to Day 90). 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 NCT04501978, which also lists 11 linked publications.

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 25 Aug 2023; AzTrials last refreshed its copy on 6 Nov 2026.

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