Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19

NCT04803227 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: EMR-COV-PR001www.pacestudies.com
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Covid19

Keywords

mild, symptomatic, COVID19

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Incidence rate of related treatment-emergent adverse events

  14 Days

Secondary Outcomes (12)

• Patient reported outcomes as assessed by COVID-19 assessment tool

  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.

  45 Days

• Number of participants the experience a related serious adverse event as assessed by CTCAE v5.0.

  45 Days

• Number of participants that experiences a Grade 3 and 4 adverse event as assessed by CTCAE v5.0

  45 Days

• Number of participants with a discontinuation or temporary suspension of study drug

  45 days

Study Arms (2)

Emricasan

ACTIVE COMPARATOR

Emricasan

Drug: Emricasan

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Emricasan DRUG

Emricasan 25 mg BID (days 1-14). Oral (capsule) administration.

Emricasan

Placebo OTHER

Placebo BID \*days 1-14). Oral (capsule) administration.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent form signed and dated by participant.
• Men or women \>/=18 years of age at the time of signing the informed consent.
• Access to device and internet for Televisits.
• 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.
• COVID-19 patients in generally healthy status without significant medical comorbidities.
• A treatment window for first dose of up to 10 days from onset of symptoms.
• 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
• \. 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).
• \. 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.
• \. 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.

You may not qualify if:

• Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening and ICU patients.
• Patients with established COVID-19 co-morbidities, other than controlled hypertension, as established by current CDC-guidelines.
• Unable to take oral medications.
• Hospitalized patients at screening.
• Moderate and severe hepatic impairment (Child-Pugh B and C) for phase 1 protocol.
• History of severe chronic respiratory disease and requirement for oxygen therapy
• 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.
• Patients with elevated baseline LFT's, such as an ALT / AST \> 2 X ULN determined by the hospital lab.
• Patients with diagnosed liver cirrhosis or clinical evidence suggestive of advanced liver disease.
• Patients with malignant tumor(s), or other serious systemic diseases.
• Patients who are participating in any other clinical studies.
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible.
• 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
• History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QTcF interval \>480 milliseconds (msec)

Sponsors & Collaborators

• Histogen: lead

Study Sites (1)

SUNY Downstate Health Sciences University

Brooklyn, New York, 11203, United States

Location

MeSH Terms

Conditions

COVID-19; Lymphoma, Follicular

Interventions

3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Raavi Gupta, MD

  SUNY Downstate

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, Placebo-controlled, Randomized, 1:1 active: placebo.

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: March 17, 2021
• Study Start: March 11, 2021
• Primary Completion: May 28, 2021
• Study Completion: May 28, 2021
• Last Updated: January 4, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)