AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)

A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H4: AZD7442)

This study looks at the safety and effectiveness of AZD7442 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a AZD7442 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H4.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: Remdesivir; Biological: Placebo; Biological: AZD7442

Detailed Description

This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of AZD7442 in hospitalized patients infected with COVID-19.

This is a randomized, blinded, controlled sub-study of AZD7442 plus current standard of care (SOC) against placebo plus current SOC. The placebo arm may be shared across other sub-studies of the ACTIV-3/TICO master protocol. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.

Randomization will be stratified by study site pharmacy and disease severity. There are 2 disease severity strata: Participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2).

An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. The pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. At the outset of the trial, only participants in disease severity stratum 1 will be enrolled. This will continue until approximately 300 participants are enrolled and followed for 5 days. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5.

If AZD7442 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. Participants will be followed for 18 months following randomization.

This trial will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

• Study Type: Interventional
• Enrollment (Actual): 1455
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Hospital (Site 625-005), Hobrovej 18
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23
  • Copenhagen Ø, Denmark, 2100
    • Righospitalet (Site 625-006), Blegdamsvej 9,
  • Herlev, Denmark, 2730
    • Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
  • Hillerød, Denmark, 3400
    • Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30
  • Kolding, Denmark, 6000
    • Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
  • Odense, Denmark, 5000
    • Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
  • Roskilde, Denmark, 4000
    • Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10
• Greece
  • 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
  • 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.
  • Athens, Greece, 115 27
    • 3rd Dept. of Medicine, Medical School, NKUA (Site 635-022), Sotiria General Hospital, 152 Mesogeion Ave.
  • 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
  • Evros
    • Alexandroupolis, Evros, Greece, 68131
      • Democritus University of Thrace (Site 635-021), University General Hospital of Alexandroupolis, Dragana
• Poland
  • Warsaw, Poland, 01-201
    • Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng
• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona (Site 626-004), Carrer de Villaroel 170
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n
  • Madrid, Spain, 28017
    • Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN
  • Madrid, Spain, 28046
    • UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n
  • Leida
    • Lleida, Leida, Spain, 25198
      • Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80
• Switzerland
  • Zurich
    • Zürich, Zurich, Switzerland, 8091
      • University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100
• Uganda
  • Entebbe, Uganda
    • MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital
  • Gulu, Uganda
    • Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160
  • Kampala, 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
  • Lira, Uganda
    • Lira Regional Referral Hospital (Site 634-605)
  • Masaka, Uganda
    • Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital (Site 634-006), Pond Street, Hampstead
  • London, United Kingdom, SE1 7EH
    • Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)
  • Northumbria
    • Newcastle Upon Tyne, Northumbria, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary (Site 634-007), Queen Victoria Road
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
    • Tucson, Arizona, United States, 85723
      • Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.
  • California
    • Chula Vista, California, United States, 91911
      • Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304
    • Fresno, California, United States, 93701
      • Community Regional Medical Center (Site 203-005), 2823 Fresno Street
    • La Mesa, California, United States, 91942
      • Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1
    • Loma Linda, California, United States, 92357
      • VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
    • Mather, California, United States, 95655
      • Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive
    • San Francisco, California, United States, 94115
      • UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
    • San Francisco, California, United States, 94121
      • San Francisco VAMC (Site 074-002), 4150 Clement St.
    • San Francisco, California, United States, 94143
      • UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.
    • Stanford, California, United States, 94305
      • Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
    • Denver, Colorado, United States, 80204
      • Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)
    • Denver, Colorado, United States, 80206
      • National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.
    • Washington, District of Columbia, United States, 20422
      • Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW
  • Florida
    • Bay Pines, Florida, United States, 33744
      • Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104
    • Clearwater, Florida, United States, 33756
      • Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street
    • Gainesville, Florida, United States, 32608-1197
      • North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street
    • Miami, Florida, United States, 33125
      • Miami VAMC (Site 074-003), 1201 NW 16 Street
    • Tampa, Florida, United States, 33602
      • Hillsborough County Health Department, University of South Florida (Site 032-001)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
  • Kansas
    • Topeka, Kansas, United States, 66604
      • Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center (Site 301-019), 22 South Greene Street
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital (Site 202-002), 55 Fruit Street
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center (Site 201-001), 759 Chestnut Street
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan (Site 205-001), 1500 East Medical Center Drive
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare (Site 027-001), 701 Park Avenue
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center (Site 112-001), 500 Harvard St. SE.
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center (Site 202-005), 2500 North State Street
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital (Site 019-001), One Cooper Plaza
  • New York
    • Bronx, New York, United States, 10451
      • Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center (Site 033-001), 450 Clarkson Ave.
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center (Site 033-002), 4802 10th Avenue
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital (Site 301-006), 2301 Erwin Road
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center (Site 108-001), 11100 Euclid Avenue
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
    • Garfield Heights, Ohio, United States, 44125
      • Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital (Site 080-036), 593 Eddy Street
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital (Site 080-039), 164 Summit Ave.
    • Providence, Rhode Island, United States, 02908
      • VA Providence Healthcare System (Site 074-025), 830 Chalkstone Ave.
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street
    • Charleston, South Carolina, United States, 29425
      • MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214
    • Florence, South Carolina, United States, 29505
      • MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
  • Texas
    • Abilene, Texas, United States, 79601
      • Hendrick Medical Center (Site 080-014), 1900 Pine Street
    • Corpus Christi, Texas, United States, 78404
      • CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street
    • Dallas, Texas, United States, 75235
      • Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
    • Dallas, Texas, United States, 75246
      • Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
    • Houston, Texas, United States, 77030
      • Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266
    • Longview, Texas, United States, 75601
      • CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital (Site 211-004), 8th Ave. C Street
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health Systems (Site 301-021), 1215 Lee Street
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital (Site 080-018), 1906 Belleview Avenue
    • Salem, Virginia, United States, 24153
      • Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Hospital First Hill (Site 208-005), 747 Broadway
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University (Site 301-023), One Medical Center Drive

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Refer to the master protocol (NCT04501978)

Exclusion Criteria:

• Refer to the master protocol (NCT04501978)

• Additional Exclusion Criteria:

  • Pregnant women
  • Nursing mothers
  • 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 the entire 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 the entire 18 months of the study.
• In addition, prior to the initial futility assessment which is performed when approximately 150 participants have been enrolled on AZD7442 and 150 on placebo, patients on highflow oxygen or non-invasive ventilation (category 5 of the pulmonary ordinal outcome) will be excluded. These patients may be eligible for the trial if the initial futility assessment is passed by this agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus SOC; Placebo administered by IV infusion; Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion	Biological: Remdesivir; Antiviral agent; Other Names: Veklury; Biological: Placebo; Commercially available 0.9% sodium chloride solution
Experimental: AZD7442 plus SOC; AZD7442 600 mg solution (separate vials containing 300 mg each of AZD88995 and AZD1061); administered by IV infusion; Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion	Biological: Remdesivir; Antiviral agent; Other Names: Veklury; Biological: AZD7442; AZD8895 and AZD1061, known collectively as AZD7442, are two fully human neutralizing immunoglobulin G (IgG)-1 kappa monoclonal antibodies (mAb) that target two distinct epitopes on the receptor-binding domain of the spike protein of SARS-CoV- 2.; Other Names: AZD8895 + AZD1061

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive outside short-term acute care hospital		Up to Day 90
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.	Days 1-7, 14 and 28
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.	Days 1-7
Change in SARS-CoV-2 neutralizing antibody levels		Baseline to Days 1, 3, 5, 28 and 90
Change in overall titers of antibodies		Baseline to Days 1, 3, 5, 28 and 90
Change in neutralizing antibody levels		Baseline to Days 1, 3, 5, 28 and 90
All-cause mortality		Through Day 90
Composite of time to sustained recovery and mortality		Through Day 90
Incidence of clinical organ failure		Through Day 28
Composite of death or serious clinical COVID-19 related events		Through Day 90
Composite of cardiovascular events and thromboembolic events		Through Day 90
Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death		Through Days 5 and 28
Incidence of infusion reactions		Through Day 0
Composite of SAEs or death		Through 18 months
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.	18 months
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.	14 days

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); AstraZeneca; University of Copenhagen; US Department of Veterans Affairs; Medical Research Council; University of Minnesota; AIDS Clinical Trials Group; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN)
• Investigators: Principal Investigator: Jens Lundgren, Prof., INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen; Study Chair: James Neaton, Prof., INSIGHT Statistical and Coordinating Centre, University of Minnesota

Publications and helpful links

General Publications

• 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;:

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2021
• Primary Completion (Actual): January 28, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus Infections; SARS-CoV-2; COVID 19; COVID-19; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; SARS Coronavirus; ACTIV-3; ACTIV3; TICO
• 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
• Other Study ID Numbers: 014/ACTIV-3/H4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No