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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05780437
• Other study ID #: 014/ACTIV-3/H4
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 5, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: March 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1455
• Est. completion date: March 31, 2023
• Est. primary completion date: January 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

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.
• Placebo
Commercially available 0.9% sodium chloride solution
• Remdesivir
Antiviral agent

Locations

Country	Name	City	State
Denmark	Aalborg Hospital (Site 625-005), Hobrovej 18	Aalborg
Denmark	Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99	Aarhus N
Denmark	Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23	Copenhagen
Denmark	Righospitalet (Site 625-006), Blegdamsvej 9,	Copenhagen Ø
Denmark	Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75	Herlev
Denmark	Nordsjællands Hospital (Site 625-009), Dyrehavevej 29	Hillerød
Denmark	Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30	Hvidovre
Denmark	Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24	Kolding
Denmark	Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4	Odense
Denmark	Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10	Roskilde
Greece	Democritus University of Thrace (Site 635-021), University General Hospital of Alexandroupolis, Dragana	Alexandroupolis	Evros
Greece	1st Respiratory Medicine Dept., Athens University Medical School (Site 635-015), Athens Hospital for Diseases of the Chest "Sotiria Hospital", 152 Mesogeion Ave.	Athens
Greece	3rd Dept. of Medicine, Medical School, NKUA (Site 635-022), Sotiria General Hospital, 152 Mesogeion Ave.	Athens
Greece	Attikon University General Hospital (Site 635-009), 4th Dept. of Internal Medicine, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari	Athens
Greece	Evangelismos COVID-19 Unit, (Site 635-020), 1st Dept. of Pulmonary and Critical Care Medicine, Evangelismos General Hospital, Dept., Ipsilantou 45-47	Athens
Poland	Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37	Warsaw
Singapore	Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng	Singapore
Spain	Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n	Badalona	Barcelona
Spain	Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170	Barcelona
Spain	Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29	Barcelona
Spain	Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129	Barcelona
Spain	Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n	Barcelona
Spain	Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80	Lleida	Leida
Spain	Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN	Madrid
Spain	Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46	Madrid
Spain	UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal	Madrid
Switzerland	University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100	Zürich	Zurich
Uganda	MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital	Entebbe
Uganda	Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160	Gulu
Uganda	Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill	Kampala
Uganda	St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146	Kampala
Uganda	Lira Regional Referral Hospital (Site 634-605)	Lira
Uganda	Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556	Masaka
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)	London
United Kingdom	Royal Free Hospital (Site 634-006), Pond Street, Hampstead	London
United Kingdom	Royal Victoria Infirmary (Site 634-007), Queen Victoria Road	Newcastle Upon Tyne	Northumbria
United States	Hendrick Medical Center (Site 080-014), 1900 Pine Street	Abilene	Texas
United States	University of Michigan (Site 205-001), 1500 East Medical Center Drive	Ann Arbor	Michigan
United States	Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE	Atlanta	Georgia
United States	University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue	Aurora	Colorado
United States	University of Maryland Medical Center (Site 301-019), 22 South Greene Street	Baltimore	Maryland
United States	Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104	Bay Pines	Florida
United States	Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.	Boston	Massachusetts
United States	Massachusetts General Hospital (Site 202-002), 55 Fruit Street	Boston	Massachusetts
United States	Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street	Bronx	New York
United States	Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street	Bronx	New York
United States	Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road	Bronx	New York
United States	Maimonides Medical Center (Site 033-002), 4802 10th Avenue	Brooklyn	New York
United States	SUNY Downstate Medical Center (Site 033-001), 450 Clarkson Ave.	Brooklyn	New York
United States	Cooper University Hospital (Site 019-001), One Cooper Plaza	Camden	New Jersey
United States	MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214	Charleston	South Carolina
United States	Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street	Charleston	South Carolina
United States	University of Virginia Health Systems (Site 301-021), 1215 Lee Street	Charlottesville	Virginia
United States	Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304	Chula Vista	California
United States	University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.	Cincinnati	Ohio
United States	Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street	Clearwater	Florida
United States	Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue	Cleveland	Ohio
United States	Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center (Site 108-001), 11100 Euclid Avenue	Cleveland	Ohio
United States	CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street	Corpus Christi	Texas
United States	Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.	Dallas	Texas
United States	Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd	Dallas	Texas
United States	UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor	Dallas	Texas
United States	Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)	Denver	Colorado
United States	National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street	Denver	Colorado
United States	Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.	Detroit	Michigan
United States	Duke University Hospital (Site 301-006), 2301 Erwin Road	Durham	North Carolina
United States	MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway	Florence	South Carolina
United States	Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard	Fort Wayne	Indiana
United States	Community Regional Medical Center (Site 203-005), 2823 Fresno Street	Fresno	California
United States	North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road	Gainesville	Florida
United States	Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road	Garfield Heights	Ohio
United States	Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street	Hollywood	Florida
United States	Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.	Houston	Texas
United States	Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266	Houston	Texas
United States	University of Mississippi Medical Center (Site 202-005), 2500 North State Street	Jackson	Mississippi
United States	Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1	La Mesa	California
United States	Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive	Lebanon	New Hampshire
United States	University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.	Lexington	Kentucky
United States	VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street	Loma Linda	California
United States	VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)	Long Beach	California
United States	CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.	Longview	Texas
United States	Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.	Los Angeles	California
United States	Keck Hospital of USC (Site 301-020), 1500 San Pablo Street	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza	Los Angeles	California
United States	Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way	Mather	California
United States	Miami VAMC (Site 074-003), 1201 NW 16 Street	Miami	Florida
United States	Hennepin Healthcare (Site 027-001), 701 Park Avenue	Minneapolis	Minnesota
United States	M Health Fairview University of Minnesota Medical Center (Site 112-001), 500 Harvard St. SE.	Minneapolis	Minnesota
United States	Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100	Minneapolis	Minnesota
United States	Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70	Minneapolis	Minnesota
United States	West Virginia University (Site 301-023), One Medical Center Drive	Morgantown	West Virginia
United States	Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street	Murray	Utah
United States	VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South	Nashville	Tennessee
United States	Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive	Nashville	Tennessee
United States	Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway	New Orleans	Louisiana
United States	Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive	Newport Beach	California
United States	UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.	Portland	Oregon
United States	Rhode Island Hospital (Site 080-036), 593 Eddy Street	Providence	Rhode Island
United States	The Miriam Hospital (Site 080-039), 164 Summit Ave.	Providence	Rhode Island
United States	VA Providence Healthcare System (Site 074-025), 830 Chalkstone Ave.	Providence	Rhode Island
United States	Carilion Roanoke Memorial Hospital (Site 080-018), 1906 Belleview Avenue	Roanoke	Virginia
United States	Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.	Salem	Virginia
United States	LDS Hospital (Site 211-004), 8th Ave. C Street	Salt Lake City	Utah
United States	University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207	Salt Lake City	Utah
United States	VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive	San Diego	California
United States	San Francisco VAMC (Site 074-002), 4150 Clement St.	San Francisco	California
United States	UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.	San Francisco	California
United States	UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.	San Francisco	California
United States	Swedish Hospital First Hill (Site 208-005), 747 Broadway	Seattle	Washington
United States	Baystate Medical Center (Site 201-001), 759 Chestnut Street	Springfield	Massachusetts
United States	Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.	Stanford	California
United States	Hillsborough County Health Department, University of South Florida (Site 032-001)	Tampa	Florida
United States	Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue	Topeka	Kansas
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building	Torrance	California
United States	Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue	Tucson	Arizona
United States	Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.	Tucson	Arizona
United States	MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.	Washington	District of Columbia
United States	Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW	Washington	District of Columbia
United States	West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue	West Haven	Connecticut
United States	Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd	Winston-Salem	North Carolina

Sponsors (13)

Lead Sponsor

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

AIDS Clinical Trials Group, AstraZeneca, Cardiothoracic Surgical Trials Network (CTSN), International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), Kirby Institute, Medical Research Council, National Heart, Lung, and Blood Institute (NHLBI), Prevention and Early Treatment of Acute Lung Injury (PETAL), University of Copenhagen, University of Minnesota, US Department of Veterans Affairs, Washington D.C. Veterans Affairs Medical Center

Countries where clinical trial is conducted

United States,  Denmark,  Greece,  Poland,  Singapore,  Spain,  Switzerland,  Uganda,  United Kingdom, 

References & 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/S2213-26 — View Citation

Outcome

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