Covid19Phase 1NCT04803227
Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19
A Phase 1 study testing Emricasan in people with Covid19, run by Histogen at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Emricasan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2021to 28 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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)
- Inability to provide informed consent or to comply with test requirements
- 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].
- Immunocompromised patients and/or patients on immunomodulators or immune suppressants other than systemic or inhaled steroids, including transplant recipients.
- 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
- If female, planned or known pregnancy - positive urine or serum pregnancy test
- Lactating or breastfeeding women
Trial locations and contacts
1 site in 1 country.
United States1 site
SUNY Downstate Health Sciences University
Brooklyn, New York, 11203
About this study
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.
Read the detailed description
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.
- Conditions
- Covid19
- Being tested
- Emricasan, Placebo
- Keywords
- mild, symptomatic, COVID19
- Medical subject headings
- COVID-19, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmricasanDrug
Emricasan 25 mg BID (days 1-14). Oral (capsule) administration.
PlaceboOther
Placebo BID *days 1-14). Oral (capsule) administration.
| Study group | Role | What they receive |
|---|---|---|
| Emricasan | Active comparator | Emricasan Receives: Drug: Emricasan |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Incidence rate of related treatment-emergent adverse events
Measured: 14 Days
Secondary outcomes (12)
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: Days 14, 30 and 45
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2021
- Study start11 Mar 2021
- Primary completion28 May 2021
- Study completion28 May 2021
Why it stopped: Unforeseeable difficulties in recruiting patients. There were no reported serious adverse events.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, Placebo-controlled, Randomized, 1:1 active: placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Histogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Raavi Gupta, MD, Principal investigator, SUNY Downstate
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04803227
- Sponsor's protocol ID
- EMR-COV-PR001
- Other IDs
- www.pacestudies.com
- Status last verified
- Dec 2021
- First submitted
- 12 Feb 2021
- Last updated
- 4 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19
- ClinicalTrials.gov ID
- NCT04803227
- Acronym / sponsor ID
- EMR-COV-PR001
- Conditions
- Covid19
- Keywords
- mild, symptomatic, COVID19
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unforeseeable difficulties in recruiting patients. There were no reported serious adverse events.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- HistogenIndustry (pharma, biotech, devices)
- Study start
- 11 Mar 2021 (actual)
- Primary completion
- 28 May 2021 (actual)
- Study completion
- 28 May 2021 (actual)
- First posted
- 17 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Double-blind, Placebo-controlled, Randomized, 1:1 active: placebo.
| Arm | Type | Receives |
|---|---|---|
| Emricasan | Active comparator | Drug: EmricasanEmricasan |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmricasanEmricasan 25 mg BID (days 1-14). Oral (capsule) administration. | Drug | Emricasan |
| PlaceboPlacebo BID *days 1-14). Oral (capsule) administration. | Other | Placebo |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 14 Days
Incidence rate of related treatment-emergent adverse events
12 secondary outcomes
Patient reported outcomes as assessed by COVID-19 assessment tool
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.
Time frame: 45 Days
Number of participants the experience a related serious adverse event as assessed by CTCAE v5.0.
Time frame: 45 Days
Number of participants that experiences a Grade 3 and 4 adverse event as assessed by CTCAE v5.0
Time frame: 45 Days
Number of participants with a discontinuation or temporary suspension of study drug
Time frame: 45 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
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.
Time frame: Days 14, 30 and 45
Each participant will perform a 6 minute walk test (6MWD) for distance (400-700m) walked.
Time frame: Days 14, 30 and 45
Each participant will be assessed for COVID-19 severity via an 8-point ordinal scale
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.
Time frame: Days 14, 30 and 45
Each participant will be tested for anti-SARS-CoV-2 quantitative antibodies via cytokine test panel.
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.
Time frame: Days 14, 30 and 45
Results and safety
The study was stopped early (reason given: Unforeseeable difficulties in recruiting patients. There were no reported serious adverse events.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raavi Gupta, MD principal investigator
SUNY Downstate
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Emricasan in people with Covid19, run by Histogen at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unforeseeable difficulties in recruiting patients. There were no reported serious adverse events.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 14 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2022.