Aprepitant Injectable Emulsion in Patients With COVID-19 (GUARDS-1)

• Aprepitant injectable emulsion (Drug): Aprepitant injectable emulsion, once daily (QD) for 14 days.
• Saline Placebo (Drug): Saline Placebo, once daily (QD) for 14 days.

Primary outcomes

• Proportion of Subjects Alive and Discharged From the Hospital. [14 Days.]: ITT Population.

Secondary outcomes

• Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO). [56 Days.]
• Time to Discharge From Hospital. [56 Days.]
• Change From Baseline in Interleukin 6 (IL-6). [Days 7, 14, 28, Discharge (from 2 to 43 days; median 6 days (Aprepitant), 8 days (Placebo))]
• Incidence of Treatment-emergent Adverse Events. [Through Day 56]: Number of subjects reporting at least on Treatment-Emergent Adverse Event. Subjects reporting more than one event are counted only once using the highest severity.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Is hospitalized for ≤48 hours with SARS-CoV-2 infection. Confirmed by polymerase chain reaction (PCR), antigen or immunoglobulin M (IgM) antibody test.
* Has at least 1 of the following: Radiographic infiltrates by imaging, or oxygen saturation of <94% by pulse oximetry on room air or requiring supplemental oxygen.
* Not anticipated to require mechanical ventilation within 48 hours.

Exclusion Criteria:

* Is taking high-dose hydroxychloroquine or chloroquine.
* Is taking pimozide or strong or moderate CYP3A4 inhibitors.
* Is currently receiving treatment with products intended to modify immune response to COVID-19 (exception: dexamethasone, methylprednisolone, or equivalent are allowed), chemotherapy or on hemodialysis or peritoneal dialysis.
* Has known hypersensitivity to any components of aprepitant injectable emulsion.
* Has evidence of ARDS.
* Is being treated with oxygen delivered by high-flow nasal cannula nonrebreather mask, noninvasive positive pressure ventilation, or ECMO.
* Has multiple organ failure.
* Has current confirmed Influenza A or B infection, or a a history of organ or hematologic transplant, HIV, or active hepatitis B or hepatitis C infection.

Participant flow

Outcome results

• Proportion of Subjects Alive and Discharged From the Hospital. (Primary), Count of participants, Participants: Treatment Group 1: Aprepitant Injectable Emulsion 11; Treatment Group 2: Placebo 10
• Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO). (Secondary), Median, days: Treatment Group 1: Aprepitant Injectable Emulsion NA (2.00 to NA); Treatment Group 2: Placebo NA (4.00 to NA)
• Time to Discharge From Hospital. (Secondary), Median, days: Treatment Group 1: Aprepitant Injectable Emulsion 6.0 (3.00 to 8.00); Treatment Group 2: Placebo 8.0 (4.00 to 11.00)
• Change From Baseline in Interleukin 6 (IL-6). (Secondary), Mean, pg/mL: Treatment Group 1: Aprepitant Injectable Emulsion 18.77 +/- 26.321; Treatment Group 2: Placebo 19.11 +/- 30.098
• Incidence of Treatment-emergent Adverse Events. (Secondary), Count of participants, Participants: Treatment Group 1: Aprepitant Injectable Emulsion 8; Treatment Group 2: Placebo 5

Adverse events

Time frame: Through Day 56.

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Study was terminated early by Heron, and was not terminated for safety reasons. The data reported is only safety data generated from the study.

• Study Protocol (PDF, 2020-12-11)
• Statistical Analysis Plan (PDF, 2021-06-22)