A Study of Brexanolone for Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease 2019 (COVID-19)

A Study of Brexanolone for Acute Respiratory Distress Syndrome Due to COVID-19

The purpose of this study was to evaluate the efficacy and safety of brexanolone in participants on ventilator support for acute respiratory distress syndrome (ARDS) due to COVID-19.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Brexanolone

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Fresno, California, United States, 93701
      • Sage Investigational Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Sage Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Sage Investigational Site
    • Burlington, Massachusetts, United States, 01805
      • Sage Investigational Site
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sage Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Sage Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Sage Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Sage Investigational Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant was confirmed positive for the novel coronavirus responsible for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection as determined by polymerase chain reaction (PCR) at Screening
• Participant had a presumptive diagnosis of ARDS at Screening and partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen [PF ratio]) less than (<) 300 prior to randomization
• Participant was intubated and receiving mechanical ventilation prior to randomization
• Participants must had initiated mechanical ventilation within 48 hours prior to screening, or had an immediate clinical plan for such intervention at time of screening
• Participant was likely to survive, in the opinion of the investigator, for at least 72 hours from the time of screening

Exclusion Criteria:

• Participant had fulminant hepatic failure at Screening
• Participant had end stage renal disease at Screening
• Participant had a known allergy to progesterone, allopregnanolone, or any excipients in the brexanolone injection
• Participant was concurrently participating in another clinical trial for an investigational product or device at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous intravenous (IV) infusion of brexanolone-matching placebo.	Drug: Placebo; Administered as IV infusion.
Experimental: Brexanolone; Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone at 70 micrograms per kilogram per hour (mcg/kg/h) for 58 hours followed by a 2-hour taper of brexanolone at 35 mcg/kg/h.	Drug: Brexanolone; Administered as IV infusion.; Other Names: Zulresso; SAGE-547; Allopregnanolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Alive and Free of Respiratory Failure at Day 28	Respiratory failure is defined based on resource utilization, requiring at least one of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20 liter/minute with fraction of delivered oxygen >=0.5), noninvasive positive pressure ventilation, and extracorporeal membrane oxygenation (ECMO). Percentage of participants who were alive and free of respiratory failure at Day 28 were reported in this outcome measure.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	An adverse event (AE) is any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. A TEAE is defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.	From first dose of investigational product up to end of study (up to Day 40)
Number of Participants Who Died Through Day 28	All cause mortality was reported up to Day 28 in this outcome measure.	From screening up to Day 28

Collaborators and Investigators

• Sponsor: Sage Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics; GABA Modulators; GABA Agents; Neurosteroids; Brexanolone; Pregnanolone
• Other Study ID Numbers: 547-ARD-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No