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 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
    Participants are no longer being randomized to this intervention.
  • Biological: BRII-196/BRII-198
    Participants are no longer being randomized to this intervention.
  • 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

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

More Details

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.