Treatments for COVID-19 are urgently needed. Emricasan (EMR) is a pan caspase inhibitor. Caspase-1 plays a role in a form of cell death called pyroptosis. EMR inhibits pyroptosis. The Investigators have shown that peripheral blood lymphocytes of COVID-19 patients overexpress caspase-1, providing evidence for pyroptosis. A recent European study corroborate the Investigators finding as they have shown evidence for the activation of the inflammasome in COVID-19.
A safety and tolerability study will be performed in 50 symptomatic outpatient mild-COVID-19 patients using Emricasan at 25mg BID dosing for 14 days with a 1:1 active: placebo of mild-COVID-19 patients receiving standard of care therapy. Although EMR has been extensively studied in humans in a total of 18 Phase 1 and Phase 2 studies, with an excellent safety and tolerance profile, it has not been used in the setting of COVID-19, therefore necessitating an initial safety and tolerability study looking at a no difference between AEs/SAEs for comparison between active and placebo group. The pharmacokinetics of EMR has been extensively studied; therefore, the Investigators will opportunistically sample patients at the end of the study to confirm that the Emricasan PK is not altered in COVID-19 patients. The primary endpoint will be cumulative incidence of AE/SAEs through day 14. Secondary endpoints will include various clinical and laboratory measures and patient reported outcomes (PROs) using a COVID-19-related assessment tool, SARS-CoV-2 viral PCR, titers of anti-SARS-CoV-2 neutralizing and quantitative antibodies and immunological studies as described in the protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
13
SUNY Downstate Health Sciences University
Brooklyn, New York, United States
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Incidence rate of related treatment-emergent adverse events
Time frame: 14 Days
Patient reported outcomes as assessed by COVID-19 assessment tool
The 2020 FDA Guidance for Industry Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment is the PRO that will be used for the study.
Time frame: At screening/randomization, daily televisits (Day 2 - Day 13), Day 14, Day 30 and Day 45
Number of participants that experience death during the study.
Rate of mortality events
Time frame: 45 Days
Number of participants the experience a related serious adverse event as assessed by CTCAE v5.0.
Cumulative incidence rate of related serious adverse events
Time frame: 45 Days
Number of participants that experiences a Grade 3 and 4 adverse event as assessed by CTCAE v5.0
Cumulative incidence rate of Grade 3 and 4 adverse events
Time frame: 45 Days
Number of participants with a discontinuation or temporary suspension of study drug
Each participant that discontinues or temporarily suspends study drug for any reason.
Time frame: 45 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Each participant will be assessed via performance of standard of care hematology and biochemistry labs. The results of the labs will be assessed against a set of normal ranges for the CLIA certified laboratory.
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Time frame: Day 1, Day 14, Day 30 and Day 45
Each participant will be tested for SARS-CoV-2 viral eradication via a sample from the nasopharynx and the sample will be tested via RT- PCR.
SARS-CoV-2 viral eradication from nasopharynx at end of treatment.
Time frame: Days 14, 30 and 45
Each participant will perform a 6 minute walk test (6MWD) for distance (400-700m) walked.
Perform 6 Minute Walk Test
Time frame: Days 14, 30 and 45
Each participant will be assessed for COVID-19 severity via an 8-point ordinal scale
COVID-19 severity score on the 8-point COVID-19 Severity Scale. Scores are from 1 to 8, where 1 = uninfected and 8 = death
Time frame: Days 14, 30 and 45
Each participant will be tested for anti-SARS-CoV-2 neutralizing antibodies via standard histogram, 2D plots, tSNE, and viSNE analysis.
The following cell populations will be examined- NK, CD4 and CD8 T-cells, Tfh, Treg, CD4 and CD8 memory, B-cell memory, monocytes and dendritic cells.
Time frame: Days 14, 30 and 45
Each participant will be tested for anti-SARS-CoV-2 quantitative antibodies via cytokine test panel.
Immune test for titers of serum anti-SARS-CoV-2 quantitative antibodies
Time frame: Days 14, 30 and 45
Each participant will be assessed for resolution of COVID19 symptoms via performance of hematology and biochemistry labs, SARS-COV-2 nasopharyngeal swab and tested via RT-PCR and immunology testing for cytokines and cell populations.
Percentage of Participants with Resolution of COVID19 symptoms
Time frame: Days 14, 30 and 45