Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Fresno, California and other locations
Dates
study started
estimated completion

Description

Summary

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.

Official Title

A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19

Details

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.

Keywords

Covid19 COVID-19 COVID 19 Coronaviridae Infections Coronavirus Infections RNA Virus Infections Virus Diseases Nidovirales Infections SARS-CoV-2 SARS Coronavirus ACTIV-3 ACTIV3 Remdesivir VIR-7831 BRII-196/BRII-198

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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).

You CAN'T join if...

  • 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:
  • stroke
  • meningitis
  • encephalitis
  • myelitis
  • myocardial ischemia
  • myocarditis
  • pericarditis
  • symptomatic congestive heart failure
  • arterial or deep venous thrombosis or pulmonary embolism
  • Current or imminent requirement for any of the following:
  • invasive mechanical ventilation
  • ECMO (extracorporeal membrane oxygenation)
  • Mechanical circulatory support
  • vasopressor therapy
  • 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.

Locations

  • Community Regional Medical Center (Site 203-005), 2823 Fresno Street accepting new patients
    Fresno California 93701 United States
  • Mount Zion Hospital, UCSF Medical Center (Site 203-007), 1600 Divisadero St. accepting new patients
    San Francisco California 94115 United States
  • Moffitt-Long Hospital, UCSF Medical Center (Site 203-001), 505 Parnassus Ave. accepting new patients
    San Francisco California 94143 United States
  • San Francisco VA Healthcare System (Site 074-002), 4150 Clement St. in progress, not accepting new patients
    San Francisco California 94121 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Links
FDA Safety Alerts and Recalls CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website A Participant's Guide to Clinical Trials (NIAID) Find a Clinical Trial (NIAID) Clinical Trials at NIAID National Institute for Allergy and Infectious Diseases (NIAID) NIH COVID-19 treatment guidelines WHO COVID-19 treatment guidelines
ID
NCT04501978
Phase
Phase 3
Study Type
Interventional
Last Updated