A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of Aprepitant Injectable Emulsion in Early Hospitalized Adult Patients with COVID-19
- Study HIC#:2000028569
- Last Updated:07/15/2021
The purpose of this research study is to see if a medicine called CINVANTI can be used safely and effectively to treat adults hospitalized because of COVID-19. Aprepitant may help in the treatment of COVID-19 because aprepitant may reduce the inflammation caused by the virus and may also reduce the ability of the virus to divide and increase in numbers. Aprepitant may also reduce the cough associated with COVID-19. All participants will receive daily treatment of study drug for up to 14 days and will be followed weekly for 8 weeks.
- Age18 years and older
- Start Date09/10/2020
- End Date02/28/2021
Each subject must meet all of the following criteria to be randomized in this study:
1. Is willing and able to, or has a legally authorized representative who is willing and able to, provide written informed consent to participate, and to cooperate with all aspects of the protocol.
2. Is ≥18 years of age at screening.
3. Is hospitalized for ≤48 hours with SARS-CoV-2 infection prior to randomization.
4. Has documented SARS-CoV-2 infection diagnostic test (polymerase chain reaction [PCR], antigen, or immunoglobulin M [IgM] antibody) prior to randomization.
5. Has at least 1 of the following:
a. Radiographic infiltrates by imaging (eg, chest X-ray, computed tomography [CT] scan),
b. Oxygen saturation (SpO2) ≤94% by pulse oximetry on room air, OR
c. Requiring supplemental oxygen.
6. Is not anticipated to require mechanical ventilation within 48 hours after randomization.
A subject who meets any of the following criteria prior to randomization will be excluded from the study:
1. Is taking high-dose hydroxychloroquine (eg, ≥400 mg twice daily [BID]) or chloroquine (eg, ≥500 mg BID) and unwilling to reduce the dose to hydroxychloroquine <400 mg BID or chloroquine <500 mg BID prior to receiving study treatment.
2. Has taken aprepitant or fosaprepitant <24 hours prior to randomization.
3. Is taking pimozide.
4. Is taking strong or moderate cytochrome P450 (CYP)3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandromycin, clarithromycin, ritonavir, nelfinavir, diltiazem) or strong CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin).
5. Is currently receiving treatment with any of the following:
a. Janus kinase (JAK) inhibitors, biologic therapies, potent immunosuppressants (including azathioprine and cyclosporine) administered with the intent to modify immune response to COVID-19 (exception: dexamethasone, methylprednisolone, or equivalent are allowed at a 50% reduction of standard dose after the start of study drug dosing), or intravenous immunoglobulin (IVIg; including convalescent plasma) at the time of consent.
c. Hemodialysis or peritoneal dialysis.
6. Has known hypersensitivity to any components of aprepitant injectable emulsion.
7. Has evidence of ARDS.
8. Has bilirubin >1.5 × the upper limit of normal (ULN), or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × ULN.
9. Has a history of long QT syndrome or a QT interval corrected using Fridericia’s formula (QTcF) >500 ms at Screening.
10. Has a medical condition or clinically significant laboratory abnormality that, in the opinion of the Investigator, would prevent participation in this clinical study.
11. Is currently participating in another study of an investigational drug or therapeutic medical device at the time of consent. Emergency Use Authorization of an investigational drug is permitted.
12. Has an expected survival <7 days.
13. Is using mechanical ventilation via tracheostomy or endotracheal intubation.
14. Is being treated with oxygen delivered by high-flow nasal cannula (>20 L/minute), nonrebreather mask, noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO).
15. Is receiving treatment with a vasopressor(s).
16. Has multiple organ failure.
17. Has current confirmed Influenza A or B infection.
18. Has a history of any of the following:
a. Organ or hematologic transplant.
c. Active hepatitis B or hepatitis C infection.
19. Female subjects are eligible only if all the following apply:
a. Not pregnant (female subjects of child-bearing potential must have a negative serum pregnancy test at Screening).
b. Not lactating.
c. Not planning to become pregnant while participating in the study.
d. Females must either practice abstinence from heterosexual contact or agree to use an acceptable form of birth control from the time of Screening, during the study, and for 28 days after the last dose of study drug. Acceptable forms of contraception include being in a monogamous relationship with a partner who is surgically sterile; practicing abstinence; or agreeing to use double-barrier contraception or a nonhormonal intrauterine device (eg, copper) in the event of sexual activity. Note: Female subjects in only a same-sex relationship do not need to meet this criterion. Hormonal contraceptives are not an acceptable form of birth control since the efficacy of hormonal contraceptives may be reduced with aprepitant.