Overview
Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19
Status:
Recruiting
Recruiting
Trial end date:
2021-06-01
2021-06-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
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.Phase:
Phase 1Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Histogen
Criteria
Inclusion Criteria:1. Informed consent form signed and dated by participant.
2. Men or women >/=18 years of age at the time of signing the informed consent.
3. Access to device and internet for Televisits.
4. Laboratory confirmed SARS-CoV-2 infection via viral RT-PCR test. The SARS-CoV-2
diagnostic test will be conducted using, if possible, an FDA acceptable product under
Emergency use Authorization (EUA) or as cleared by the Center for Device and
Radiological Health (CDRH). We will have confirmation of the SARS-CoV-2 testing prior
to enrollment.
5. COVID-19 patients in generally healthy status without significant medical
comorbidities.
6. A treatment window for first dose of up to 10 days from onset of symptoms.
7. Outpatients with symptoms of respiratory illness caused by coronavirus 2019 infection
as defined below:
- Symptoms of mild illness with COVID-19 as defined by the W.H.O. in Table 1of the
Clinical Management of COVID-19 interim Guidance document, May 27, 2020, meeting
the case definition for mild COVID-19 without evidence of viral pneumonia or
hypoxia
- COVID-19 severity score on an 8-point ordinal score =/< 2 as defined by the WHO
2020. 8. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal,
considered not clinically significant by the Principal Investigator. 9. Normal or
clinically insignificant change in the liver (ALT, AST) and kidney function (blood
creatinine), CBC with differential and clotting factors (PT and PTT).
10. Understands and agrees to comply with planned study procedures. 11. Women of
childbearing potential must agree to use at least one medically accepted method of
contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel],
hormonal contraceptives [implants, injectables, combination oral contraceptives,
transdermal patches, or contraceptive rings], or intrauterine devices) for the duration of
the study.
12. Background standard of care will be maintained in all treatment arms. Off-label use of
any other drugs, devices, or interventions that might be used to manage COVID-19 need to be
discussed with the study medical director.
Exclusion Criteria:
1. Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory
failure necessitating mechanical ventilation at the time of screening and ICU
patients.
2. Patients with established COVID-19 co-morbidities, other than controlled hypertension,
as established by current CDC-guidelines.
3. Unable to take oral medications.
4. Hospitalized patients at screening.
5. Moderate and severe hepatic impairment (Child-Pugh B and C) for phase 1 protocol.
6. History of severe chronic respiratory disease and requirement for oxygen therapy
7. Any uncontrolled active systemic infection (e.g. cellulitis or abscess) or infections
requiring admission to an intensive care unit (ICU). Note: Subjects infected with
HIV-1 will be eligible for the study with undetectable viral load and are on a stable
ART regimen. Investigators are required to review the subjects' medical records to
confirm HIV-1 RNA suppression within the previous 3 months.
Note: Empirical antibiotic treatment for secondary bacterial infections is allowed
during the course of study.
8. Patients with elevated baseline LFT's, such as an ALT / AST > 2 X ULN determined by
the hospital lab.
9. Patients with diagnosed liver cirrhosis or clinical evidence suggestive of advanced
liver disease.
10. Patients with malignant tumor(s), or other serious systemic diseases.
11. Patients who are participating in any other clinical studies.
12. Patients who have a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to leronlimab (PRO 140) are not eligible.
13. Current use of the following medications that are considered significant inhibitors of
OATP1B1 and OATP1B3 transporters: atazanavir, cyclosporine, eltrombopag, gemfibrozil,
indinavir, lopinavir, ritonavir, rifampin, saquinavir, simeprevir, telaprevir,
tipranovir, or some combination of these medications
14. History or presence of clinically concerning cardiac arrhythmias, or prolongation of
Screening (pre-treatment) QTcF interval >480 milliseconds (msec)
15. Inability to provide informed consent or to comply with test requirements
16. Moderate or higher level of severity of COVID-19. Moderate COVID-19 defined as:
Symptoms of moderate illness with COVID-19, which could include any symptom of mild
illness or shortness of breath with exertion, but clinical signs suggestive of
moderate illness with COVID-19 including, respiratory rate ≥ 25 breaths per minute, or
saturation of oxygen (SpO2) < 93% on room air at sea level, or resting heart rate ≥ 90
beats per minute (unless related to fever). In elderly patient population normal
resting respiratory rate is 16-25 [24].
17. Immunocompromised patients and/or patients on immunomodulators or immune suppressants
other than systemic or inhaled steroids, including transplant recipients.
18. Evidence of any new or uncontrolled concomitant disease that, in the investigator's
judgment, would preclude patient participation, including but not limited to
cardiovascular, pulmonary, nervous system, renal, hepatic, endocrine, malignant, or
gastrointestinal disorders
19. If female, planned or known pregnancy - positive urine or serum pregnancy test
20. Lactating or breastfeeding women