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

NCT05780437 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 014/ACTIV-3/H4
• Study Type: interventional
• Target: 1,455
• Locations: 9 countries
• Sites: 124

Brief Summary

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.

Conditions

COVID-19

Keywords

COVID-19; COVID 19; Coronaviridae Infections; Coronavirus Infections; RNA Virus Infections; Virus Diseases; Nidovirales Infections; SARS-CoV-2; SARS Coronavirus; ACTIV-3; ACTIV3; TICO

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Sustained Recovery

  The primary endpoint is the proportion of subjects with sustained recovery, which is defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90. Home is defined as the level of residence or facility where the participant was residing prior to hospital admission leading to enrollment in this protocol. Readmission from "home" may occur, and if this occurs within 14 days of the first discharge to "home," then the primary endpoint will not be reached until such time as the participant has been at home for 14 consecutive days.

  Through Day 90

• Number of Participants With an Ordinal Outcome on Day 5

  Ordinal outcome with 7 mutually exclusive categories

  Status on Day 5

Secondary Outcomes (4)

• Number of Participants With a Safety Outcome Through Day 5

  Through Day 5

• Number of Participants With a Safety Outcome Through Day 28

  Through Day 28

• Number of Participants With a Safety Outcome Through Day 90

  Through Day 90

• Number of Participants Who Died From All Causes

  Through Day 90

Study Arms (2)

AZD7442 plus SOC

EXPERIMENTAL

* AZD7442 600 mg solution (4 separate vials, 2 containing 150 mg each of AZD88995 and 2 containing 150 mg each of 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: AZD7442; Biological: Remdesivir

Placebo plus SOC

PLACEBO COMPARATOR

* Placebo administered by IV infusion * Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion

Biological: Placebo; Biological: Remdesivir

Interventions

AZD7442 BIOLOGICAL

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.

Also known as: AZD8895 + AZD1061

AZD7442 plus SOC

Placebo BIOLOGICAL

Commercially available 0.9% sodium chloride solution

Placebo plus SOC

Remdesivir BIOLOGICAL

Antiviral agent

Also known as: Veklury

AZD7442 plus SOC; Placebo plus SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Refer to the master protocol (NCT04501978)

You may not qualify if:

• Refer to the master protocol (NCT04501978)
• 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 high-flow 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• International Network for Strategic Initiatives in Global HIV Trials (INSIGHT): collaborator
• University of Copenhagen: collaborator
• Medical Research Council: collaborator
• Kirby Institute: collaborator
• Washington D.C. Veterans Affairs Medical Center: collaborator
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• US Department of Veterans Affairs: collaborator
• Prevention and Early Treatment of Acute Lung Injury: collaborator
• Cardiothoracic Surgical Trials Network: collaborator
• AstraZeneca: collaborator
• University of Minnesota: collaborator

Study Sites (124)

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

Tucson, Arizona, 85719, United States

Location

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

Tucson, Arizona, 85723, United States

Location

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

Chula Vista, California, 91911, United States

Location

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

Fresno, California, 93701, United States

Location

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

La Mesa, California, 91942, United States

Location

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

Loma Linda, California, 92357, United States

Location

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

Long Beach, California, 90822, United States

Location

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

Los Angeles, California, 90033, United States

Location

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

Los Angeles, California, 90048, United States

Location

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

Los Angeles, California, 90095, United States

Location

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

Mather, California, 95655, United States

Location

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

Newport Beach, California, 92663, United States

Location

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

San Diego, California, 92161, United States

Location

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

San Francisco, California, 94115, United States

Location

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

San Francisco, California, 94121, United States

Location

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

San Francisco, California, 94143, United States

Location

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

Stanford, California, 94305, United States

Location

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

Torrance, California, 90502, United States

Location

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

Aurora, Colorado, 80045, United States

Location

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

Denver, Colorado, 80204, United States

Location

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

Denver, Colorado, 80206, United States

Location

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

West Haven, Connecticut, 06516, United States

Location

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

Washington D.C., District of Columbia, 20010, United States

Location

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

Washington D.C., District of Columbia, 20422, United States

Location

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

Bay Pines, Florida, 33744, United States

Location

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

Clearwater, Florida, 33756, United States

Location

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

Gainesville, Florida, 32608-1197, United States

Location

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

Hollywood, Florida, 33021, United States

Location

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

Miami, Florida, 33125, United States

Location

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

Tampa, Florida, 33602, United States

Location

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

Atlanta, Georgia, 30322, United States

Location

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

Fort Wayne, Indiana, 46804, United States

Location

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

Topeka, Kansas, 66604, United States

Location

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

Lexington, Kentucky, 40536, United States

Location

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

New Orleans, Louisiana, 70121, United States

Location

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

Baltimore, Maryland, 21201, United States

Location

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

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02215, United States

Location

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

Springfield, Massachusetts, 01199, United States

Location

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

Ann Arbor, Michigan, 48109, United States

Location

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

Detroit, Michigan, 48202, United States

Location

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

Minneapolis, Minnesota, 55407, United States

Location

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

Minneapolis, Minnesota, 55415, United States

Location

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

Minneapolis, Minnesota, 55417, United States

Location

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

Minneapolis, Minnesota, 55455, United States

Location

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

Jackson, Mississippi, 39216, United States

Location

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

Lebanon, New Hampshire, 03756, United States

Location

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

Camden, New Jersey, 08103, United States

Location

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

Brooklyn, New York, 11203, United States

Location

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

Brooklyn, New York, 11219, United States

Location

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

The Bronx, New York, 10451, United States

Location

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

The Bronx, New York, 10461, United States

Location

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

The Bronx, New York, 10467, United States

Location

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

Durham, North Carolina, 27710, United States

Location

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

Winston-Salem, North Carolina, 27157, United States

Location

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

Cincinnati, Ohio, 45219, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

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

Cleveland, Ohio, 44111, United States

Location

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

Cleveland, Ohio, 44195, United States

Location

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

Garfield Heights, Ohio, 44125, United States

Location

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

Portland, Oregon, 97239-3098, United States

Location

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

Pittsburgh, Pennsylvania, 15213, United States

Location

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

Pittsburgh, Pennsylvania, 15213, United States

Location

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

Pittsburgh, Pennsylvania, 15232, United States

Location

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

Providence, Rhode Island, 02903, United States

Location

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

Providence, Rhode Island, 02906, United States

Location

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

Providence, Rhode Island, 02908, United States

Location

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

Charleston, South Carolina, 29401, United States

Location

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

Charleston, South Carolina, 29425, United States

Location

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

Florence, South Carolina, 29505, United States

Location

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

Nashville, Tennessee, 37212, United States

Location

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

Nashville, Tennessee, 37232, United States

Location

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

Abilene, Texas, 79601, United States

Location

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

Corpus Christi, Texas, 78404, United States

Location

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

Dallas, Texas, 75235, United States

Location

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

Dallas, Texas, 75235, United States

Location

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

Dallas, Texas, 75246, United States

Location

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

Houston, Texas, 77030, United States

Location

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

Houston, Texas, 77030, United States

Location

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

Longview, Texas, 75601, United States

Location

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

Murray, Utah, 84107, United States

Location

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

Salt Lake City, Utah, 84108, United States

Location

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

Salt Lake City, Utah, 84143, United States

Location

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

Charlottesville, Virginia, 22903, United States

Location

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

Roanoke, Virginia, 24014, United States

Location

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

Salem, Virginia, 24153, United States

Location

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

Seattle, Washington, 98122, United States

Location

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

Morgantown, West Virginia, 26506, United States

Location

Aalborg Hospital (Site 625-005), Hobrovej 18

Aalborg, 9000, Denmark

Location

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

Aarhus N, 8200, Denmark

Location

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

Copenhagen, 2400, Denmark

Location

Righospitalet (Site 625-006), Blegdamsvej 9,

Copenhagen Ø, 2100, Denmark

Location

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

Herlev, 2730, Denmark

Location

Nordsjællands Hospital (Site 625-009), Dyrehavevej 29

Hillerød, 3400, Denmark

Location

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

Hvidovre, 2650, Denmark

Location

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

Kolding, 6000, Denmark

Location

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

Odense, 5000, Denmark

Location

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

Roskilde, 4000, Denmark

Location

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

Alexandroupoli, Evros, 68131, Greece

Location

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, Greece

Location

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, Greece

Location

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

Athens, 115 27, Greece

Location

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, Greece

Location

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

Warsaw, 01-201, Poland

Location

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

Singapore, 308433, Singapore

Location

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

Badalona, Barcelona, 08916, Spain

Location

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

Lleida, Leida, 25198, Spain

Location

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

Barcelona, 08003, Spain

Location

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

Barcelona, 08035, Spain

Location

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

Barcelona, 08036, Spain

Location

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

Barcelona, 08907, Spain

Location

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

Madrid, 28017, Spain

Location

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

Madrid, 28040, Spain

Location

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

Madrid, 28046, Spain

Location

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

Zurich, Canton of Zurich, 8091, Switzerland

Location

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

Entebbe, Uganda

Location

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

Gulu, Uganda

Location

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

Kampala, Uganda

Location

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

Kampala, Uganda

Location

Lira Regional Referral Hospital (Site 634-605)

Lira, Uganda

Location

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

Masaka, Uganda

Location

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

Newcastle upon Tyne, Northumbria, NE1 4LP, United Kingdom

Location

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

London, NW3 2QG, United Kingdom

Location

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

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35817072 RESULT

MeSH Terms

Conditions

COVID-19; Coronaviridae Infections; Coronavirus Infections; RNA Virus Infections; Virus Diseases; Nidovirales Infections; Severe Acute Respiratory Syndrome

Interventions

cilgavimab and tixagevimab drug combination; remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Greg Grandits
• Organization: University of Minnesota

greg-g@ccbr.umn.edu

651-528-9491

Study Officials

• Jens Lundgren, Prof.

  INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen

  PRINCIPAL INVESTIGATOR

• James Neaton, Prof.

  INSIGHT Statistical and Data Management Center, University of Minnesota

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: March 22, 2023
• Study Start: February 10, 2021
• Primary Completion: January 28, 2022
• Study Completion: June 9, 2023
• Last Updated: February 4, 2025
• Results First Posted: July 30, 2024

Record last verified: 2025-01

Locations

PL (1); DK (10); ES (9); GR (5); UG (6); US (88); SG (1); CH (1); GB (3)