This will be a phase 1a randomized, open label, multi-center study with approximately 24 subjects. All subjects will receive standard of care (SOC) per institutional guidelines for treatment of hospitalized patients with COVID-19 infection. In addition to SOC, the brequinar group will receive 5 daily doses of brequinar 100 mg.
This will be a phase 1a randomized, open label, multi-center study with approximately 24
subjects. All subjects will receive standard of care (SOC) per institutional guidelines for
SARS-CoV-2 infection. Subjects will be randomly assigned in a 1:2 ratio to SOC alone or SOC
plus brequinar. The SOC plus brequinar group will receive 5 daily doses of brequinar 100 mg
on Days 1 - 5 in addition to SOC. Physical examinations, vital signs, laboratory assessments,
SARS-CoV-2 testing, and other observations will be conducted by experienced personnel
throughout the study based on the Schedule of Events. Blood chemistry tests include blood
urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), alanine amino transferase (ALT),
aspartate amino transferase (AST), bilirubin, total protein, albumin, glucose, serum
electrolytes (sodium, potassium, chloride, carbon dioxide/bicarbonate, and calcium), lactate
dehydrogenase (LDH). Plasma will be collected for inflammatory markers such as D-dimer,
ferritin, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
Pro-inflammatory markers will be measured. Serum is to be collected for research purposes.
Hematology tests include hemoglobin, hematocrit, complete blood count with full differential,
and platelet count. Nasopharyngeal swabs for viral load will be collected Days 1, 3, 5, 7,
and 15. Survival will be assessed through Day 29.
Drug: Brequinar
DHODH inhibitor, 100 mg daily x 5 days
Other Name: Standard of Care + Brequinar
Other: Standard of Care
Standard of Care per institutional guidelines for COVID-19 patients
Inclusion Criteria:
1. Willing and able to provide informed consent for the trial, written, electronic,
verbal or other method deemed acceptable by the institution and IRB.
2. 18 years of age or older.
3. If discharged from the hospital prior to Study Day 15 or if follow up is needed for
study drug-related adverse event, willing to go to an outpatient facility if feasible
or be in contact with the study team (phone call or other digital media) for remaining
study assessments.
4. Laboratory-confirmed SARS-CoV-2 infection as determined by real time polymerase chain
reaction (RT-PCR) or other Food and Drug Administration (FDA)-cleared commercial or
public health assay.
5. Hospitalized (in patient with expected duration ≥ 24 hours)
6. The effects of brequinar on the developing human fetus are unknown. For this reason,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Men and women treated or enrolled on this protocol
must also agree to use adequate contraception for the duration of study participation
and for 90 days after completion of brequinar administration.
7. Male subjects must agree to refrain from sperm donation from initial study drug
administration until 90 days after the last dose of brequinar.
8. ≤ 10 days since first COVID-19 symptom as determined by treating clinician.
9. Able to swallow capsules.
10. At least one COVID-19 symptom including but not limited to fever, cough, sore throat,
malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath,
dyspnea, dysgeusia, or other symptom commonly associated with COVID-19.
Exclusion Criteria:
1. Any physical examination findings and/or history of any illness that, in the opinion
of the study investigator, might confound the results of the study or pose an
additional risk to the patient.
2. Active malignancy other than squamous cell carcinoma; anticancer treatment such as
chemotherapy or radiation therapy within the past month.
3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy
test.
4. Treatment with another DHODH inhibitor (e.g., leflunomide or teriflunomide),
tacrolimus, sirolimus.
5. Platelets ≤150,000 cell/mm3.
6. Hemoglobin < 10 gm/dL
7. Absolute neutrophil count < 1500 cells/mm3
8. Renal dysfunction, i.e., creatinine clearance < 30 mL/min
9. AST and/or ALT > 1.5 ULN, or total bilirubin > ULN
10. History of bleeding disorders or recent surgery in the six weeks preceding enrollment
11. Concomitant use of agents known to cause bone marrow suppression leading to
thrombocytopenia
12. History of gastrointestinal ulcer, or history of gastrointestinal bleeding.
13. History of hepatitis B and/or C infection, active liver disease and/or cirrhosis.
14. Heart failure, current uncontrolled cardiovascular disease, including unstable angina,
uncontrolled arrhythmias, major adverse cardiac event within 6 months (e.g. stroke,
myocardial infarction, hospitalization due to heart failure, or revascularization
procedure).
15. Life expectancy of < 5 days in the judgment of the treating clinician.
16. Evidence of critical illness defined by at least one of the following:
a. Respiratory failure requiring at least one of the following: i. Endotracheal
intubation and mechanical ventilation, noninvasive positive pressure ventilation,
ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the
preceding therapies, but preceding therapies may not be able to be administered in
setting of resource limitation) ii. Shock (defined by systolic blood pressure < 90 mm
Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressors) b. Multi-organ
dysfunction/failure.
Hartford Hospital
Hartford, Connecticut, United States
Baptist Medical Center
Jacksonville, Florida, United States
University of South Florida/Tampa General
Tampa, Florida, United States
University of New Mexico
Albuquerque, New Mexico, United States
Temple University
Philadelphia, Pennsylvania, United States