Acute Respiratory Distress Syndrome, COVID-19
Conditions
Brief summary
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.
Interventions
DRUGBrexanolone
Administered as IV infusion.
DRUGPlacebo
Administered as IV infusion.
Sponsors
Sage Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Are Alive and Free of Respiratory Failure at Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | From first dose of investigational product up to end of study (up to Day 40) | 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. |
| Number of Participants Who Died Through Day 28 | From screening up to Day 28 | All cause mortality was reported up to Day 28 in this outcome measure. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled in the study at 9 centers in the United States from 18 December 2020 to 01 July 2021.
Pre-assignment details
A total of 33 participants were screened of which 29 were randomized and 28 were dosed. This study consisted of up to a 2-day screening period, a 60-hour treatment period plus an additional follow-up of up to 23 days.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone-matching placebo. | 14 |
| Brexanolone Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone at 70 mcg/kg/h for 58 hours followed by a 2-hour taper of brexanolone at 35 mcg/kg/h. | 14 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Randomized but not treated | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Brexanolone | Total |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.81 | 58.2 years STANDARD_DEVIATION 12.79 | 60.4 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 10 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 14 | 8 / 14 |
| other Total, other adverse events | 11 / 14 | 11 / 14 |
| serious Total, serious adverse events | 8 / 14 | 8 / 14 |
Outcome results
Primary
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.
Time frame: Day 28
Population: FAS included all randomized participants who initiated IP (brexanolone or placebo). Here, Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Are Alive and Free of Respiratory Failure at Day 28 | 23.1 percentage of participants |
| Brexanolone | Percentage of Participants Who Are Alive and Free of Respiratory Failure at Day 28 | 23.1 percentage of participants |
p-value: 195% CI: [-31.8, 31.8]Chi-squared
Secondary
Number of Participants Who Died Through Day 28
All cause mortality was reported up to Day 28 in this outcome measure.
Time frame: From screening up to Day 28
Population: Safety analysis set included all participants who initiated IP (brexanolone or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Died Through Day 28 | 6 Participants |
| Brexanolone | Number of Participants Who Died Through Day 28 | 8 Participants |
Secondary
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.
Time frame: From first dose of investigational product up to end of study (up to Day 40)
Population: Safety analysis set included all participants who initiated IP (brexanolone or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 13 Participants |
| Brexanolone | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 14 Participants |