NCT04501978

ACTIV-3: Therapeutics for Inpatients With COVID-19

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,753 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Covid19

Interventions

Type	Name	Description
BIOLOGICAL	LY3819253	Participants are no longer being randomized to this intervention.
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.
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	Participants are no longer being randomized to this intervention.
DRUG	MP0420	Participants are no longer being randomized to this intervention.
DRUG	PF-07304814	250 mg per day for 5 days. Administered as a constant rate intravenous infusion. Suspended: Participants are not currently being randomized to this intervention.

Timeline

• Start date: 2020-08-04
• Primary completion: 2022-04-06
• Completion: 2023-07-14
• First posted: 2020-08-06
• Last updated: 2023-08-25

Locations

135 sites across 10 countries: United States, Denmark, Greece, Nigeria, Poland, Singapore, Spain, Switzerland, Uganda, United Kingdom

Regulatory

• FDA-regulated drug study