Purpose

This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Signed informed consent. - Positive test for COVID-19 and progressive disease suggestive of ongoing COVID-19 infection. - Symptoms of COVID-19 for ≤ 12 days. - Require admission to hospital for acute medical care (not for purely public health or quarantine purposes).

Exclusion Criteria

  • Patients who have received plasma from a person who recovered from COVID-19 or who have received neutralizing monoclonal antibodies at any time prior to hospitalization. - Patients not willing to abstain from participation in other COVID-19 treatment trials until after Day 5 of the study. Co-enrollment in certain trials that compare recommended Standard of Care treatments may be allowed, based on the opinion of the study leadership team. - Any condition which, in the opinion of the responsible investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments. - Patients considered unable to participate in study procedures. - Women of child-bearing potential who are not already pregnant at study entry and who are unwilling to acknowledge strong advice to abstain from sexual intercourse with men or practice appropriate contraception through 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 18 months of the study. - Presence at study enrollment of any of the following: 1. stroke 2. meningitis 3. encephalitis 4. myelitis 5. myocardial ischemia 6. myocarditis 7. pericarditis 8. symptomatic congestive heart failure 9. arterial or deep venous thrombosis or pulmonary embolism - Current or imminent requirement for any of the following: 1. invasive mechanical ventilation 2. ECMO (extracorporeal membrane oxygenation) 3. Mechanical circulatory support 4. vasopressor therapy 5. commencement of renal replacement therapy at this admission (i.e. not patients on chronic renal replacement therapy). - Study drug VIR-7831: Pregnant and/or nursing women. - Study drug BRII-196/BRII-198: Pregnant and/or nursing women. - Study drug VIR-7831: Prior to initial assessment (150 participants enrolled to receive VIR-7831, 150 participants enrolled to receive placebo), patients on high-flow oxygen or non-invasive ventilation. These patients may be eligible for the study if the initial assessment is passed. - Study drug BRII-196/BRII-198: Prior to initial assessment (150 participants enrolled to receive BRII-196/BRII-198, 150 participants enrolled to receive placebo), patients on high-flow oxygen or non-invasive ventilation. These patients may be eligible for the study if the initial assessment is passed. Other investigational drug protocol-defined inclusion/exclusion criteria may apply.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ACTIV-3 Drug plus SOC
Participants in this study will be randomized to receive one of the ACTIV-3 drug treatments plus Standard of Care (SOC) or placebo plus SOC
  • Biological: LY3819253
    Participants are no longer being randomized to this intervention.
  • Biological: Remdesivir
    Provided to all study participants as SOC unless contraindicated for an individual patient.
  • Biological: VIR-7831
    Administered by IV infusion
  • Biological: BRII-196/BRII-198
    Administered by IV infusion
  • Biological: AZD7442
    600 mg AZD7442 (300 mg AZD8895 + 300 mg AZD1061). Administered by IV infusion as a single dose.
    Other names:
    • AZD8895 + AZD1061
Placebo Comparator
Placebo plus SOC
The placebo arm may be pooled across more than one experimental arm if multiple investigational drugs are available to be tested at the same time. If it is not possible to use matching placebo over more than one experimental arm, additional placebo arms will be included in the study
  • Drug: Placebo
    Commercially available 0.9% sodium chloride solution. Administered by IV infusion
  • Biological: Remdesivir
    Provided to all study participants as SOC unless contraindicated for an individual patient.

Recruiting Locations

Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
Tucson, Arizona 85719
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Southern Arizona VA Health Care System (Site 074-009), 3601 S. 6th Ave.
Tucson, Arizona 85723
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email, and send to
ticova@insight-trials.org

Community Regional Medical Center (Site 203-005), 2823 Fresno Street
Fresno, California 93701
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
Loma Linda, California 92357
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticova@insight-trials.org

Keck Hospital of USC (Site 301-020), 1500 San Pablo Street
Los Angeles, California 90033
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.
Los Angeles, California 90048
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Mount Zion Hospital, UCSF Medical Center (Site 203-007), 1600 Divisadero St.
San Francisco, California 94115
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

San Francisco VA Healthcare System (Site 074-002), 4150 Clement St.
San Francisco, California 94121
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticova@insight-trials.org

Moffitt-Long Hospital, UCSF Medical Center (Site 203-001), 505 Parnassus Ave.
San Francisco, California 94143
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Stanford University Hospital & Cinics (Site 203-003), 300 Pasteur Dr.
Stanford, California 94305
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
Aurora, Colorado 80045
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Denver Public Health (Site 017-004), 605 Bannock St., MC2600 (Infectious Disease Clinic)
Denver, Colorado 80204
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW
Washington, District of Columbia 20007
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

VA Medical Center (Site 009-004), 50 Irving Street NW
Washington, District of Columbia 20422
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

Bay Pines VA Healthcare System (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104
Bay Pines, Florida 33744
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticova@insight-trials.org

Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street
Clearwater, Florida 33756
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street
Hollywood, Florida 33021
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticonih@insight-trials.org

Miami VA Healthcare System (Site 074-003), 1201 NW 16 Street
Miami, Florida 33125
Contact:
If interested in participating at this site, enter site name and ACITV-3 in subject line of email and send to
ticowdc@insight-trials.org

The Emory Clinic (Site 301-008), Bldg. A, Suite 2236, 1365 Clifton Rd., NE
Atlanta, Georgia 30322
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard
Fort Wayne, Indiana 46804
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.
Lexington, Kentucky 40536
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway
New Orleans, Louisiana 70121
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

University of Maryland (Site 301-019), 22 South Greene Street
Baltimore, Maryland 21201
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Baystate Medical Center (Site 201-001), 759 Chestnut Street
Springfield, Massachusetts 01199
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

University of Michigan (Site 205-001), 1500 East Medical Center Drive
Ann Arbor, Michigan 48109
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.
Detroit, Michigan 48202
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

Hennepin Healthcare (Site 027-001), 701 Park Avenue
Minneapolis, Minnesota 55415
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70
Minneapolis, Minnesota 55417
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

University of Mississippi Medical Center (Site 202-005), 2500 North State Street
Jackson, Mississippi 39216
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road
Bronx, New York 10461
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street
Bronx, New York 10467
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Duke University Hospital (Site 301-006), 2301 Erwin Road
Durham, North Carolina 27710
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd
Winston-Salem, North Carolina 27157
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.
Cincinnati, Ohio 45219
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue
Cleveland, Ohio 44111
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue
Cleveland, Ohio 44195
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road
Garfield Heights, Ohio 44125
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
Portland, Oregon 97239-3098
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street
Pittsburgh, Pennsylvania 15213
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
Nashville, Tennessee 37232
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor
Dallas, Texas 75235
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
Dallas, Texas 75246
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.
Houston, Texas 77030
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticowdc@insight-trials.org

Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
Murray, Utah 84107
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

University of Utah Health (Site 211-002), 419 Wakara Way, Suite 207
Salt Lake City, Utah 84108
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

LDS Hospital (Site 211-004), 8th Ave. C Street
Salt Lake City, Utah 84143
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

University of Virginia (Site 301-021), 1215 Lee Street
Charlottesville, Virginia 22903
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.
Salem, Virginia 24153
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticova@insight-trials.org

Swedish Medical Center (Site 208-005), 747 Broadway
Seattle, Washington 98122
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticopetal@insight-trials.org

WVU Medicine (Site 301-023), One Medical Center Drive
Morgantown, West Virginia 26506
Contact:
If interested in participating at this site, enter site name and ACTIV-3 in subject line of email and send to
ticoctsn@insight-trials.org

More Details

NCT ID
NCT04501978
Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

If interested in participating in this study, please contact the appropriate site or
send email to
tico@insight-trials.org

Detailed Description

This is a master protocol to evaluate the safety and efficacy of multiple investigational agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly enhancing viral control in order to limit disease progression. The protocol is for a randomized, blinded, controlled platform study that allows investigational drugs to be added and dropped during the course of the study. This allows for efficient testing of new drugs against placebo and standard of care (SOC) treatment within the same study. 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. For investigational drugs with minimal pre-existing safety knowledge, the pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. For the study of each agent, 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. Both ordinal outcomes are used to assess futility because it is currently unclear whether the investigational agents under study will primarily influence non-pulmonary outcomes, for which risk is increased with SARS-CoV-2 infection, in part, through mechanisms that may be different from those that influence pulmonary outcomes. For investigational agents passing this 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. The international trials within this protocol 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.