BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)

NCT05780424 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 014/ACTIV-3/H3
• Study Type: interventional
• Target: 353
• Locations: 8 countries
• Sites: 107

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Who Died From All Causes

  Through Day 90

• 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

Study Arms (2)

BRII-196/BRII-198 plus SOC

EXPERIMENTAL

* BRII-196 1000 mg solution; administered as IV infusion * BRII-198 1000 mg solution; administered as IV infusion * Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion

Biological: BRII-196; Biological: BRII-198; 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

BRII-196 BIOLOGICAL

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-196/BRII-198 plus SOC

BRII-198 BIOLOGICAL

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.

BRII-196/BRII-198 plus SOC

Placebo BIOLOGICAL

Commercially available 0.9% sodium chloride solution

Placebo plus SOC

Remdesivir BIOLOGICAL

Antiviral agent

Also known as: Veklury

BRII-196/BRII-198 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
• 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.

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
• Brii Biosciences Limited: collaborator
• University of Minnesota: collaborator

Study Sites (107)

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

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

Fresno, California, 93701, 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

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

Newport Beach, California, 92663, 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

MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW

Washington D.C., District of Columbia, 20007, 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

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

Jackson, Mississippi, 39216, United States

Location

VA St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201

St Louis, Missouri, 63106, 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

Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620

New York, New York, 10029, 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

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

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

Charleston, South Carolina, 29425, 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

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

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

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. 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.

  PMID: 34953520 RESULT

MeSH Terms

Conditions

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

Interventions

amubarvimab; romlusevimab; 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: December 16, 2020
• Primary Completion: June 8, 2021
• Study Completion: October 10, 2022
• Last Updated: February 5, 2024
• Results First Posted: February 5, 2024

Record last verified: 2024-02

Locations

US (76); PL (1); ES (9); UG (6); SG (1); GB (3); DK (10); CH (1)