Duvelisib to Combat COVID-19

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: Duvelisib
Drug: Placebo
Procedure: Peripheral blood draw

Registration Number: NCT04372602

Lead Sponsor: Washington University School of Medicine

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-Placebo 25 mg twice daily for up to 10 days.
Duvelisib	Peripheral blood draw	-Duvelisib 25 mg twice daily for up to 10 days.
Placebo	Peripheral blood draw	-Placebo 25 mg twice daily for up to 10 days.
Duvelisib	Duvelisib	-Duvelisib 25 mg twice daily for up to 10 days.

Primary Outcome Measures

Name	Time	Method
Overall Survival as Measured by Number of Participants Alive Through 28 Days	Through 28 days

Secondary Outcome Measures

Name	Time	Method
Length of ICU Stay	Through 28 days
Duration on Renal Replacement Therapy	Through 28 days
Number of Adverse Events as Measured by CTCAE v. 5.0	Through 29 days
Length of Hospital Stay	Through 28 days
Duration of Ventilator Use	Through 28 days	-For those on a ventilator at the time of randomization
Duration of Vasopressors Use	Through 28 days
Viral Kinetics as Measured by Virologic Failure	Through 28 days	-Defined as increase in viral load of \>0.5 log on two consecutive days, or \>1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing