Clinical trial NCT05780424: BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: COVID-19
COVID 19
Coronaviridae Infections
Coronavirus Infections
RNA Virus Infections
Virus Infections
Nidovirales Infections
SARS-CoV-2
SARS Coronavirus
ACTIV-3
ACTIV3
TICO
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
name: University of Copenhagen
name: Medical Research Council
name: Kirby Institute
name: Washington D.C. Veterans Affairs Medical Center
name: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
name: National Heart, Lung, and Blood Institute (NHLBI)
name: US Department of Veterans Affairs
name: Prevention and Early Treatment of Acute Lung Injury
name: Cardiothoracic Surgical Trials Network
name: Brii Biosciences Limited
name: University of Minnesota
First posted: 2023-03-22
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With an Ordinal Outcome on Day 5
timeFrame: Status on Day 5
Secondary outcomes:
measure: Number of Participants Who Died From All Causes
timeFrame: Through Day 90
measure: Number of Participants With a Safety Outcome Through Day 5
timeFrame: Through Day 5
measure: Number of Participants With a Safety Outcome Through Day 28
timeFrame: Through Day 28
measure: Number of Participants With a Safety Outcome Through Day 90
timeFrame: Through Day 90
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.
state: Arizona
city: Fresno
country: United States
facility: Community Regional Medical Center (Site 203-005), 2823 Fresno Street
state: California
city: Loma Linda
country: United States
facility: VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC (Site 074-002), 4150 Clement St.
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.
state: California
city: Stanford
country: United States
facility: Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
state: Colorado
city: Denver
country: United States
facility: Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)
state: Colorado
city: Denver
country: United States
facility: National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street
state: Colorado
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW
state: District of Columbia
city: Bay Pines
country: United States
facility: Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104
state: Florida
city: Clearwater
country: United States
facility: Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street
state: Florida
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street
state: Florida
city: Miami
country: United States
facility: Miami VAMC (Site 074-003), 1201 NW 16 Street
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Department, University of South Florida (Site 032-001)
state: Florida
city: Atlanta
country: United States
facility: Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE
state: Georgia
city: Fort Wayne
country: United States
facility: Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
state: Indiana
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center (Site 301-019), 22 South Greene Street
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (Site 202-002), 55 Fruit Street
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center (Site 201-001), 759 Chestnut Street
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan (Site 205-001), 1500 East Medical Center Drive
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin Healthcare (Site 027-001), 701 Park Avenue
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center (Site 202-005), 2500 North State Street
state: Mississippi
city: Saint Louis
country: United States
facility: VA St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital (Site 019-001), One Cooper Plaza
state: New Jersey
city: Bronx
country: United States
facility: Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
state: New York
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620
state: New York
city: Durham
country: United States
facility: Duke University Hospital (Site 301-006), 2301 Erwin Road
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
state: Ohio
city: Garfield Heights
country: United States
facility: Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital (Site 080-036), 593 Eddy Street
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital (Site 080-039), 164 Summit Ave.
state: Rhode Island
city: Charleston
country: United States
facility: MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214
state: South Carolina
city: Nashville
country: United States
facility: VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
state: Tennessee
city: Corpus Christi
country: United States
facility: CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street
state: Texas
city: Dallas
country: United States
facility: Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
state: Texas
city: Dallas
country: United States
facility: Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266
state: Texas
city: Longview
country: United States
facility: CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital (Site 211-004), 8th Ave. C Street
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health Systems (Site 301-021), 1215 Lee Street
state: Virginia
city: Salem
country: United States
facility: Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.
state: Virginia
city: Seattle
country: United States
facility: Swedish Hospital First Hill (Site 208-005), 747 Broadway
state: Washington
city: Morgantown
country: United States
facility: West Virginia University (Site 301-023), One Medical Center Drive
state: West Virginia
city: Aalborg
country: Denmark
facility: Aalborg Hospital (Site 625-005), Hobrovej 18
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99
city: Copenhagen Ø
country: Denmark
facility: Righospitalet (Site 625-006), Blegdamsvej 9,
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23
city: Herlev
country: Denmark
facility: Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital (Site 625-009), Dyrehavevej 29
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30
city: Kolding
country: Denmark
facility: Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24
city: Odense
country: Denmark
facility: Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10
city: Warsaw
country: Poland
facility: Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n
state: Barcelona
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80
state: Leida
city: Barcelona
country: Spain
facility: Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN
city: Madrid
country: Spain
facility: UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal
city: Zürich
country: Switzerland
facility: University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100
state: Zurich
city: Entebbe
country: Uganda
facility: MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital
city: Gulu
country: Uganda
facility: Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160
city: Kampala
country: Uganda
facility: Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill
city: Kampala
country: Uganda
facility: St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146
city: Lira
country: Uganda
facility: Lira Regional Referral Hospital (Site 634-605)
city: Masaka
country: Uganda
facility: Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary (Site 634-007), Queen Victoria Road
state: Northumbria
city: London
country: United Kingdom
facility: Royal Free Hospital (Site 634-006), Pond Street, Hampstead
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)
Study officials:
affiliation: INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
name: Jens Lundgren, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: INSIGHT Statistical and Data Management Center, University of Minnesota
name: James Neaton, Prof.
role: STUDY_CHAIR
References:
citation: 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.