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NCT05780424 Clinical Trial

BRII-196/BRII-198 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 H3: BRII-196/BRII-198)

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT05780424
Other study ID # 014/ACTIV-3/H3
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date December 16, 2020
Est. completion date October 10, 2022

Study information
Verified date February 2024
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study looks at the safety and effectiveness of BRII-196/BRII-198 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either BRII-196/BRII-198 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H3.

Description:

This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of BRII-196/BRII-198 in hospitalized patients infected with COVID-19. This is a randomized, blinded, controlled sub-study of BRII-196/BRII-198 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 BRII-196/BRII-198 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 Completed
Enrollment 353
Est. completion date October 10, 2022
Est. primary completion date June 8, 2021
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 - In addition, prior to the initial futility assessment which is performed when approximately 150 participants have been enrolled on BRII-196/BRII-198 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.

Study Design

Related Conditions & MeSH terms

Intervention

Biological:
• BRII-196
BRII-196 is a fully human immunoglobulin G (IgG)-1 monoclonal antibody (mAb) derived from antibody P2C-1F11 that was isolated directly from human B cells of a convalescent COVID-19 patient.
• BRII-198
BRII-198 is a fully human IgG-1 mAb derived from antibody P2B-1G5 that was isolated directly from human B cells of a convalescent COVID-19 patient.
• 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
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 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 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 University of Virginia Health Systems (Site 301-021), 1215 Lee Street Charlottesville Virginia
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 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 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 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 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 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 Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620 New York New York
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 St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201 Saint Louis Missouri
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 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 Georgetown University Hospital (Site 067-001), 3800 Reservoir Road 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 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, Brii Biosciences Limited, Cardiothoracic Surgical Trials Network, 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, 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,  Poland,  Singapore,  Spain,  Switzerland,  Uganda,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary Number of Participants With an Ordinal Outcome on Day 5 Ordinal outcome with 7 mutually exclusive categories Status on Day 5
Secondary Number of Participants Who Died From All Causes All-cause mortality Through Day 90
Secondary Number of Participants With a Safety Outcome Through Day 5 Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5 Through Day 5
Secondary Number of Participants With a Safety Outcome Through Day 28 Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28 Through Day 28
Secondary Number of Participants With a Safety Outcome Through Day 90 Death, SAE, clinical organ failure, serious infections through Day 90 Through Day 90
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