Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a 2-part, multi-center, randomized, double-blind, placebo-controlled, phase 2 study
designed to evaluate the safety, tolerability, and efficacy of oral varespladib, in addition
to standard of care, in patients hospitalized with severe COVID-19 caused by SARS-CoV-2.
Phase
Phase 2
Funding Agency/Sponsor
Industry
Disease
Other
Enrollment Eligibility
Inclusion Criteria:
1. Participant is hospitalized with severe COVID-19 illness, defined in accordance with
the Food and Drug Administration (FDA) Guidance for Industry - COVID-19: Developing
Drugs and Biological Products for Treatment or Prevention (May 2020):
a. Severe illness:
i. Symptoms suggestive of severe systemic illness with COVID-19, which could include
any symptom of moderate illness or shortness of breath at rest, or respiratory
distress
ii. Clinical signs indicative of severe systemic illness with COVID-19, such as
respiratory rate ≥30 per minute, heart rate ≥125 per minute, SpO₂ ≤93% on room air at
sea level or partial pressure of oxygen PaO₂/fraction of inspired oxygen FiO₂ <300.
2. Participant has a positive virologic nucleic acid amplification test (NAAT) indicating
SARS-CoV-2 infection in a sample collected <72 hours prior to randomization.
3. Participant is between the ages of 18 and 80 years at the time of enrollment.
4. Participant provides informed consent prior to initiation of any study procedures.
5. Participant agrees to not participate in another clinical trial for the treatment of
COVID 19 or SARS-CoV-2 through Day 28.
6. Participant has adequate hematologic status (in the absence of transfusion and growth
factor support for at least 28 days), defined as follows:
1. Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
2. Platelet count ≥75 × 10⁹/L
3. Hemoglobin ≥9 g/dL.
7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
Exclusion Criteria:
1. Participant has mild, moderate, or critical COVID-19 defined in accordance with the
FDA Guidance for Industry:
a. Mild COVID-19:
i. Symptoms of mild illness with COVID-19 that could include fever, cough, sore
throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness
of breath or dyspnea
ii. No clinical signs indicative of moderate, severe, or critical severity
b. Moderate COVID-19:
i. Symptoms of moderate illness with COVID-19, which could include any symptom of mild
illness (fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal
symptoms) or shortness of breath with exertion
ii. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory
rate ≥20 breaths per minute, peripheral oxygen saturation (SpO₂) >93% on room air at
sea level, heart rate ≥90 beats per minute
iii. No clinical signs indicative of severe or critical illness
c. Critical COVID-19:
i. Respiratory failure defined based on resource utilization requiring at least one of
the following:
- Endotracheal intubation and mechanical ventilation
- Oxygen delivered by high-flow nasal cannula ([HFNC] heated, humidified, oxygen
delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of
delivered oxygen ≥0.5)
- Noninvasive positive pressure ventilation
- ECMO, or
- Clinical diagnosis of respiratory failure (i.e., clinical need for one of the
preceding therapies, but preceding therapies not able to be administered in
setting of resource limitation)
ii. Shock (defined by systolic blood pressure <90 mmHg, or diastolic blood pressure
<60 mmHg or requiring vasopressors)
iii. Multi-organ dysfunction/failure.
2. Participant has taken investigational medications within 7 days or 5 half-lives prior
to enrollment, whichever is shorter.
3. Participant has required any new form of sedation, anxiolysis or central nervous
system (CNS) depressant within the 48 hours prior to enrollment that would interfere
with neurologic assessments at enrollment.
4. Has history of cerebrovascular accident or intracranial bleeding of any kind, acute
coronary syndrome, myocardial infarction, or severe pulmonary hypertension.
5. Participant has chronic respiratory failure not associated with COVID-19, defined as
prior need for home oxygen, need for home noninvasive positive-pressure ventilation
(NIPPV) for reasons other than isolated sleep apnea, or other signs of chronic
respiratory failure, in the investigator's judgment.
6. Upper gastrointestinal (GI) bleed evidenced by hematemesis, "coffee-ground" emesis or
nasogastric aspirate, or hematochezia thought to originate from upper GI tract.
7. Participant has abnormal liver function defined as any 2 of the following at
screening:
1. Total bilirubin ≥2 × ULN
2. Alanine aminotransferase (ALT) ≥3 × ULN
3. Aspartate aminotransferase (AST) ≥3 × ULN
4. Alkaline phosphatase (ALP) >3 × ULN
5. Gamma-glutamyl transferase (GGT) >3 × ULN
8. Participant has an estimated glomerular filtration rate (eGFR) <60 mL/min.
9. Participant has a known allergy or significant adverse reaction to varespladib-methyl
or related compounds.
10. Participant is considered by the investigator to be unable to comply with protocol
requirements due to geographic considerations, psychiatric disorders, or other
compliance concerns; or has any serious medical condition or clinically significant
laboratory, ECG, vital sign, or physical examination abnormality that would prevent
study participation or place the participant at significant risk, as judged by the
Investigator.
11. Participant is breast-feeding, pregnant, has a positive serum hCG pregnancy test, or
is not willing to use a highly effective method of contraception for 14 days after
treatment. Highly effective methods of contraception are as follows:
1. Combined (estrogen- and progestogen-containing) hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, or transdermal)
2. Progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, or implantable)
3. Intrauterine device, intrauterine hormone-releasing system
4. Bilateral tubal occlusion
5. Vasectomized partner
6. Sexual abstinence
7. Double-barrier method (condoms, sponge, diaphragm, with spermicidal jellies, or
cream).