Trial Outcomes & Findings for A Study of Brexanolone for Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease 2019 (COVID-19) (NCT NCT04537806)

Last Updated: 2022-08-19

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

29 participants

Primary outcome timeframe

Day 28

Results posted on

2022-08-19

Participant Flow

Participants were enrolled in the study at 9 centers in the United States from 18 December 2020 to 01 July 2021.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	15	14
Overall Study Safety Analysis Set	14	14
Overall Study Full Analysis Set	14	14
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Randomized but not treated	1	0
Overall Study Adverse Event	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=14 Participants Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone-matching placebo.	Brexanolone n=14 Participants 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.	Total n=28 Participants Total of all reporting groups
Age, Continuous	62.6 years STANDARD_DEVIATION 9.81 • n=5 Participants	58.2 years STANDARD_DEVIATION 12.79 • n=7 Participants	60.4 years STANDARD_DEVIATION 11.40 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone-matching placebo.	Brexanolone n=13 Participants 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.
Percentage of Participants Who Are Alive and Free of Respiratory Failure at Day 28	23.1 percentage of participants	23.1 percentage of participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone-matching placebo.	Brexanolone n=14 Participants 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.
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	13 Participants	14 Participants

SECONDARY outcome

Timeframe: From screening up to Day 28

Population: Safety analysis set included all participants who initiated IP (brexanolone or placebo).

All cause mortality was reported up to Day 28 in this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone-matching placebo.	Brexanolone n=14 Participants 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.
Number of Participants Who Died Through Day 28	6 Participants	8 Participants

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 11 other events

Deaths: 7 deaths

Brexanolone

Serious events: 8 serious events

Other events: 11 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Monitor

Sage Therapeutics

Phone: (617) 299-8380

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=14 participants at risk Participants receiving mechanical ventilation as standard of care were randomized to receive a 60-hour single continuous IV infusion of brexanolone-matching placebo.	Brexanolone n=14 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	21.4% 3/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	28.6% 4/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	21.4% 3/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	21.4% 3/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Cardiac disorders Atrial fibrillation	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Cardiac disorders Acute myocardial infarction	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Cardiac disorders Cardiac arrest	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Nervous system disorders Encephalopathy	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	14.3% 2/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Nervous system disorders Cerebellar infarction	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Nervous system disorders Cerebral infarction	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Infections and infestations COVID-19	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Infections and infestations Pneumonia serratia	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Infections and infestations Septic shock	14.3% 2/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Infections and infestations Pneumonia	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Infections and infestations Sepsis	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
General disorders Multiple organ dysfunction syndrome	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Surgical and medical procedures Endotracheal intubation	14.3% 2/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Gastrointestinal disorders Intra-abdominal haematoma	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).
Vascular disorders Deep vein thrombosis	7.1% 1/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).	0.00% 0/14 • From screening up to end of study (up to Day 40) Safety analysis set included all participants who initiated IP (brexanolone or placebo).