VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)
Study Details
Study Description
Brief Summary
This study looks at the safety and effectiveness of VIR-7831 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either VIR-7831 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H2.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of VIR-7831 in hospitalized patients infected with COVID-19.
This is a randomized, blinded, controlled sub-study of VIR-7831 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 VIR-7831 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: VIR-7831 plus SOC VIR-7831 500 mg solution (2 vials of 250 mg); administered as a single IV infusion Remdesivir is provided to all study participants as SOC unless contraindicated for an individual patient; administered by IV infusion |
Biological: VIR-7831
VIR-7831 is a fully human neutralizing immunoglobulin G (IgG)-1 kappa monoclonal antibody (mAb) derived from antibody S309 from a survivor of SARS-CoV-1.
Biological: Remdesivir
Antiviral agent
Other Names:
|
Placebo Comparator: Placebo plus SOC 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
Commercially available 0.9% sodium chloride solution
Biological: Remdesivir
Antiviral agent
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Time from randomization to sustained recovery [Up to Day 90]
Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
Secondary Outcome Measures
- All-cause mortality [Through Day 90]
- Composite of time to sustained recovery and mortality [Through Day 90]
- Days alive outside short-term acute care hospital [Up to Day 90]
- Pulmonary ordinal outcome [Days 1-7, 14 and 28]
Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
- Pulmonary+ ordinal outcome [Days 1-7]
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.
- Incidence of clinical organ failure [Through Day 28]
- Composite of death or serious clinical COVID-19 related events [Through Day 90]
- Composite of cardiovascular events and thromboembolic events [Through Day 90]
- Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death [Through Days 5 and 28]
- Incidence of infusion reactions [Through Day 0]
- Composite of SAEs or death [Through 18 months]
- Change in SARS-CoV-2 neutralizing antibody levels [Baseline to Days 1, 3, 5, 28 and 90]
- Change in overall titers of antibodies [Baseline to Days 1, 3, 5, 28 and 90]
- Change in neutralizing antibody levels [Baseline to Days 1, 3, 5, 28 and 90]
- Incidence of home use of supplemental oxygen above pre-morbid oxygen use [18 months]
Measured as: Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14-day period.
- Incidence of no home use of supplemental oxygen above pre-morbid oxygen use [14 days]
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.
Eligibility Criteria
Criteria
Inclusion Criteria: Refer to the master protocol (NCT04501978)
Exclusion Criteria: Refer to the master protocol (NCT04501978)
Additional Exclusion Criteria:
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Pregnant women
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Nursing mothers
In addition, prior to the initial futility assessment which is performed when approximately 150 participants have been enrolled on VIR-7831 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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue | Tucson | Arizona | United States | 85719 |
2 | Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave. | Tucson | Arizona | United States | 85723 |
3 | Community Regional Medical Center (Site 203-005), 2823 Fresno Street | Fresno | California | United States | 93701 |
4 | VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street | Loma Linda | California | United States | 92357 |
5 | VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2) | Long Beach | California | United States | 90822 |
6 | Keck Hospital of USC (Site 301-020), 1500 San Pablo Street | Los Angeles | California | United States | 90033 |
7 | Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd. | Los Angeles | California | United States | 90048 |
8 | Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza | Los Angeles | California | United States | 90095 |
9 | Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive | Newport Beach | California | United States | 92663 |
10 | UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St. | San Francisco | California | United States | 94115 |
11 | San Francisco VAMC (Site 074-002), 4150 Clement St. | San Francisco | California | United States | 94121 |
12 | UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave. | San Francisco | California | United States | 94143 |
13 | Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr. | Stanford | California | United States | 94305 |
14 | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building | Torrance | California | United States | 90502 |
15 | University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue | Aurora | Colorado | United States | 80045 |
16 | Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic) | Denver | Colorado | United States | 80204 |
17 | National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street | Denver | Colorado | United States | 80206 |
18 | MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW | Washington | District of Columbia | United States | 20007 |
19 | Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW | Washington | District of Columbia | United States | 20422 |
20 | Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104 | Bay Pines | Florida | United States | 33744 |
21 | Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street | Clearwater | Florida | United States | 33756 |
22 | North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road | Gainesville | Florida | United States | 32608-1197 |
23 | Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street | Hollywood | Florida | United States | 33021 |
24 | Miami VAMC (Site 074-003), 1201 NW 16 Street | Miami | Florida | United States | 33125 |
25 | Hillsborough County Health Department, University of South Florida (Site 032-001) | Tampa | Florida | United States | 33602 |
26 | Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE | Atlanta | Georgia | United States | 30322 |
27 | Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard | Fort Wayne | Indiana | United States | 46804 |
28 | Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue | Topeka | Kansas | United States | 66604 |
29 | University of Kentucky Hospital (Site 210-004), 1000 South Limestone St. | Lexington | Kentucky | United States | 40536 |
30 | Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway | New Orleans | Louisiana | United States | 70121 |
31 | University of Maryland Medical Center (Site 301-019), 22 South Greene Street | Baltimore | Maryland | United States | 21201 |
32 | Massachusetts General Hospital (Site 202-002), 55 Fruit Street | Boston | Massachusetts | United States | 02114 |
33 | Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave. | Boston | Massachusetts | United States | 02215 |
34 | Baystate Medical Center (Site 201-001), 759 Chestnut Street | Springfield | Massachusetts | United States | 01199 |
35 | University of Michigan (Site 205-001), 1500 East Medical Center Drive | Ann Arbor | Michigan | United States | 48109 |
36 | Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd. | Detroit | Michigan | United States | 48202 |
37 | Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100 | Minneapolis | Minnesota | United States | 55407 |
38 | Hennepin Healthcare (Site 027-001), 701 Park Avenue | Minneapolis | Minnesota | United States | 55415 |
39 | Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70 | Minneapolis | Minnesota | United States | 55417 |
40 | University of Mississippi Medical Center (Site 202-005), 2500 North State Street | Jackson | Mississippi | United States | 39216 |
41 | Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive | Lebanon | New Hampshire | United States | 03756 |
42 | Cooper University Hospital (Site 019-001), One Cooper Plaza | Camden | New Jersey | United States | 08103 |
43 | Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street | Bronx | New York | United States | 10451 |
44 | Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road | Bronx | New York | United States | 10461 |
45 | Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street | Bronx | New York | United States | 10467 |
46 | Duke University Hospital (Site 301-006), 2301 Erwin Road | Durham | North Carolina | United States | 27710 |
47 | Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd | Winston-Salem | North Carolina | United States | 27157 |
48 | University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave. | Cincinnati | Ohio | United States | 45219 |
49 | Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue | Cleveland | Ohio | United States | 44111 |
50 | Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue | Cleveland | Ohio | United States | 44195 |
51 | Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road | Garfield Heights | Ohio | United States | 44125 |
52 | Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd. | Portland | Oregon | United States | 97239-3098 |
53 | UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street | Pittsburgh | Pennsylvania | United States | 15213 |
54 | UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street | Pittsburgh | Pennsylvania | United States | 15213 |
55 | UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue | Pittsburgh | Pennsylvania | United States | 15232 |
56 | Rhode Island Hospital (Site 080-036), 593 Eddy Street | Providence | Rhode Island | United States | 02903 |
57 | The Miriam Hospital (Site 080-039), 164 Summit Ave. | Providence | Rhode Island | United States | 02906 |
58 | MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214 | Charleston | South Carolina | United States | 29425 |
59 | VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South | Nashville | Tennessee | United States | 37212 |
60 | Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive | Nashville | Tennessee | United States | 37232 |
61 | CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street | Corpus Christi | Texas | United States | 78404 |
62 | Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd | Dallas | Texas | United States | 75235 |
63 | UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor | Dallas | Texas | United States | 75235 |
64 | Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave. | Dallas | Texas | United States | 75246 |
65 | Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd. | Houston | Texas | United States | 77030 |
66 | Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266 | Houston | Texas | United States | 77030 |
67 | CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave. | Longview | Texas | United States | 75601 |
68 | Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street | Murray | Utah | United States | 84107 |
69 | University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207 | Salt Lake City | Utah | United States | 84108 |
70 | LDS Hospital (Site 211-004), 8th Ave. C Street | Salt Lake City | Utah | United States | 84143 |
71 | University of Virginia Health Systems (Site 301-021), 1215 Lee Street | Charlottesville | Virginia | United States | 22903 |
72 | Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd. | Salem | Virginia | United States | 24153 |
73 | Swedish Hospital First Hill (Site 208-005), 747 Broadway | Seattle | Washington | United States | 98122 |
74 | West Virginia University (Site 301-023), One Medical Center Drive | Morgantown | West Virginia | United States | 26506 |
75 | Aalborg Hospital (Site 625-005), Hobrovej 18 | Aalborg | Denmark | 9000 | |
76 | Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99 | Aarhus N | Denmark | 8200 | |
77 | Righospitalet (Site 625-006), Blegdamsvej 9, | Copenhagen Ø | Denmark | 2100 | |
78 | Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23 | Copenhagen | Denmark | 2400 | |
79 | Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75 | Herlev | Denmark | 2730 | |
80 | Nordsjællands Hospital (Site 625-009), Dyrehavevej 29 | Hillerød | Denmark | 3400 | |
81 | Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30 | Hvidovre | Denmark | 2650 | |
82 | Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24 | Kolding | Denmark | 6000 | |
83 | Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4 | Odense | Denmark | 5000 | |
84 | Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10 | Roskilde | Denmark | 4000 | |
85 | Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37 | Warsaw | Poland | 01-201 | |
86 | Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng | Singapore | Singapore | 308433 | |
87 | Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n | Badalona | Barcelona | Spain | 08916 |
88 | Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80 | Lleida | Leida | Spain | 25198 |
89 | Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29 | Barcelona | Spain | 08003 | |
90 | Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129 | Barcelona | Spain | 08035 | |
91 | Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170 | Barcelona | Spain | 08036 | |
92 | Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n | Barcelona | Spain | 08907 | |
93 | Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46 | Madrid | Spain | 28017 | |
94 | Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN | Madrid | Spain | 28040 | |
95 | UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal | Madrid | Spain | 28046 | |
96 | University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100 | Zürich | Zurich | Switzerland | 8091 |
97 | MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital | Entebbe | Uganda | ||
98 | Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160 | Gulu | Uganda | ||
99 | Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill | Kampala | Uganda | ||
100 | St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146 | Kampala | Uganda | ||
101 | Lira Regional Referral Hospital (Site 634-605) | Lira | Uganda | ||
102 | Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556 | Masaka | Uganda | ||
103 | Royal Victoria Infirmary (Site 634-007), Queen Victoria Road | Newcastle Upon Tyne | Northumbria | United Kingdom | NE1 4LP |
104 | Royal Free Hospital (Site 634-006), Pond Street, Hampstead | London | United Kingdom | NW3 2QG | |
105 | Guy's and St. Thomas' NHS Foundation Trust (Site 634-011) | London | United Kingdom | SE1 7EH |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
- University of Copenhagen
- Medical Research Council
- Kirby Institute
- Washington D.C. Veterans Affairs Medical Center
- AIDS Clinical Trials Group
- National Heart, Lung, and Blood Institute (NHLBI)
- US Department of Veterans Affairs
- Prevention and Early Treatment of Acute Lung Injury (PETAL)
- Cardiothoracic Surgical Trials Network (CTSN)
- Vir Biotechnology, Inc.
- GlaxoSmithKline
- University of Minnesota
Investigators
- Principal Investigator: Jens Lundgren, Prof., INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
- Study Chair: James Neaton, Prof., INSIGHT Statistical and Coordinating Centre, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 014/ACTIV-3/H2