COVID-19
Conditions
Keywords
COVID-19, Coronavirus
Brief summary
The study will evaluate the efficacy and safety of aprepitant injectable emulsion added to standard of care for hospitalized patients with COVID-19.
Interventions
DRUGAprepitant injectable emulsion
Aprepitant injectable emulsion, once daily (QD) for 14 days.
DRUGSaline Placebo
Saline Placebo, once daily (QD) for 14 days.
Sponsors
Heron Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Alive and Discharged From the Hospital. | 14 Days. | ITT Population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
One participant was prematurely randomized while failing screening eligibility. This subject was counted in both 'Screen Failures' and 'Randomized Subjects/ITT population', leading to a discrepancy between the Enrollment number in the Protocol Section (27) and the number of participants Started in the Participant Flow module (26).
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1: Aprepitant Injectable Emulsion Aprepitant injectable emulsion, 130 mg QD for 14 days. | 12 |
| Treatment Group 2: Placebo Saline Placebo, QD for 14 days. | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | Treatment Group 2: Placebo | Treatment Group 1: Aprepitant Injectable Emulsion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 6 Participants | 16 Participants |
| Age, Continuous | 57.7 years STANDARD_DEVIATION 11.93 | 61.8 years STANDARD_DEVIATION 15.64 | 59.7 years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 12 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 21 Participants |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 1 / 14 |
| other Total, other adverse events | 8 / 12 | 5 / 13 |
| serious Total, serious adverse events | 2 / 12 | 2 / 13 |
Outcome results
Primary
Proportion of Subjects Alive and Discharged From the Hospital.
ITT Population.
Time frame: 14 Days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1: Aprepitant Injectable Emulsion | Proportion of Subjects Alive and Discharged From the Hospital. | 11 Participants |
| Treatment Group 2: Placebo | Proportion of Subjects Alive and Discharged From the Hospital. | 10 Participants |
Secondary
Change From Baseline in Interleukin 6 (IL-6).
Time frame: Days 7, 14, 28, Discharge (from 2 to 43 days; median 6 days (Aprepitant), 8 days (Placebo))
Population: Overall Number of Participants Analyzed reflects the Total Enrolled ITT Population whereas Number Analyzed in each row reflects the number of subjects with IL-6 data reported at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group 1: Aprepitant Injectable Emulsion | Change From Baseline in Interleukin 6 (IL-6). | Day 7 | -27.98 pg/mL | Standard Deviation 42.493 |
| Treatment Group 1: Aprepitant Injectable Emulsion | Change From Baseline in Interleukin 6 (IL-6). | Day 28 | -8.00 pg/mL | — |
| Treatment Group 1: Aprepitant Injectable Emulsion | Change From Baseline in Interleukin 6 (IL-6). | Day 14 | 124.00 pg/mL | — |
| Treatment Group 1: Aprepitant Injectable Emulsion | Change From Baseline in Interleukin 6 (IL-6). | Discharge | -17.41 pg/mL | Standard Deviation 30.754 |
| Treatment Group 1: Aprepitant Injectable Emulsion | Change From Baseline in Interleukin 6 (IL-6). | Baseline | 18.77 pg/mL | Standard Deviation 26.321 |
| Treatment Group 2: Placebo | Change From Baseline in Interleukin 6 (IL-6). | Discharge | -9.68 pg/mL | Standard Deviation 18.107 |
| Treatment Group 2: Placebo | Change From Baseline in Interleukin 6 (IL-6). | Baseline | 19.11 pg/mL | Standard Deviation 30.098 |
| Treatment Group 2: Placebo | Change From Baseline in Interleukin 6 (IL-6). | Day 7 | 14.83 pg/mL | Standard Deviation 65.384 |
| Treatment Group 2: Placebo | Change From Baseline in Interleukin 6 (IL-6). | Day 14 | 204.30 pg/mL | Standard Deviation 407.244 |
| Treatment Group 2: Placebo | Change From Baseline in Interleukin 6 (IL-6). | Day 28 | 2.90 pg/mL | — |
Secondary
Incidence of Treatment-emergent Adverse Events.
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.
Time frame: Through Day 56
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1: Aprepitant Injectable Emulsion | Incidence of Treatment-emergent Adverse Events. | 8 Participants |
| Treatment Group 2: Placebo | Incidence of Treatment-emergent Adverse Events. | 5 Participants |
Secondary
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).
Time frame: 56 Days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Group 1: Aprepitant Injectable Emulsion | 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). | NA days |
| Treatment Group 2: Placebo | 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). | NA days |
Secondary
Time to Discharge From Hospital.
Time frame: 56 Days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Group 1: Aprepitant Injectable Emulsion | Time to Discharge From Hospital. | 6.0 days |
| Treatment Group 2: Placebo | Time to Discharge From Hospital. | 8.0 days |