Duvelisib to Combat COVID-19
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Duvelisib; Peripheral blood draw; Placebo
Intervention description: -For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.; First 10 patients enrolled
Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29; -Provided by Verastem
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Blocks of 10 patients will be used to allocate patients to duvelisib or placebo
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: COVID-19

Summary:

      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.
    

Eligibility criteria:

        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.