The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.
Drug: Duvelisib
-For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.
Other Name: Copiktra
Procedure: Peripheral blood draw
First 10 patients enrolled
Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29
Drug: Placebo
-Provided by Verastem
Inclusion Criteria:
- A diagnosis of advanced COVID-19 as defined both of the following:
- as a positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper
respiratory tract (e.g. nasopharyngeal, nasal, oropharyngeal swab, or saliva)
and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or
bronchoalveolar lavage), analyzed by a CLIA certified lab with an FDA approved
assay.
- Critical disease manifested by any of the following:
- Chest imaging with ≥ 50% lung involvement
- Respiratory failure requiring invasive mechanical ventilation, non-invasive
mechanical ventilation (eg. BiPAPA, OptiFlow), supplementary oxygen with
FiO2 ≥ 6 LPM or extracorporeal membrane oxygenation (ECMO)
- Shock - defined as mean arterial pressure ≤ 65 mmHg unresponsive to 25ml/kg
isotonic intravenous fluid resuscitation and/or requiring vasopressor
support
- Cardiac dysfunction defined by:
- New global systolic dysfunction with ejection fraction ≤ 40%
- Takotsubo cardiomyopathy
- Patients who have received prior investigational or off-label agents for COVID-19 does
not exclude eligibility.
- At least 18 years of age at the time of study registration
- Adequate hematologic function defined as absolute neutrophil count ≥1000/mm3 and
platelet count ≥ 50,000/mm3 without growth factor or transfusion support for 7 days
prior to screening.
- Creatinine-clearance ≥ 15 mL/minute or receiving renal replacement therapy
- Aminotransferase (AST/ALT) levels <3x the upper limit of normal
- Able to understand and willing to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable)
- Women of childbearing potential (defined as women with regular menses, women with
amenorrhea, women with irregular cycles, women using a contraceptive method that
precludes withdrawal bleeding, or women who have had a tubal ligation) are required to
have a negative pregnancy test and use two forms of acceptable contraception,
including one barrier method, during participation in the study treatment period.
- Male patients if engaging in sex with a women of childbearing potential are required
to use two forms of acceptable contraception, including one barrier method, during
participation in the study and throughout the evaluation period.
Exclusion Criteria:
- Known allergy or intolerance to duvelisib or another PI3K inhibitor.
- Known or suspected active viral (including CMV, HIV, hepatitis B, and hepatitis C),
bacterial, mycobacterial, or fungal infection other than COVID-19. CMV viral load will
be assessed at screening and those with viremia will be excluded. Other virologic
testing not required unless infection is suspected.
- Pregnant and/or breastfeeding.
- Any uncontrolled intercurrent illness that would put the patient at greater risk or
limit compliance with study requirements in the opinion of the investigator.
Washington University School of Medicine
Saint Louis, Missouri, United States
John DiPersio, M.D., Ph.D., Principal Investigator
Washington University School of Medicine