Duvelisib to Combat COVID-19

Study Overview
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Brief Summary
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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.

Official Title
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A Pilot Study of Duvelisib to Combat COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Duvelisib
* Procedure: Peripheral blood draw
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duvelisib<br>-Duvelisib 25 mg twice daily for up to 10 days. | Drug: Duvelisib<br>* -For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.<br>* Other names: Copiktra;Procedure: Peripheral blood draw<br>* First 10 patients enrolled Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29<br>|
| Sham Comparator: Placebo<br>-Placebo 25 mg twice daily for up to 10 days. | Procedure: Peripheral blood draw<br>* First 10 patients enrolled Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29<br>Drug: Placebo<br>* -Provided by Verastem<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival as Measured by Number of Participants Alive Through 28 Days |  | Through 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Hospital Stay |  | Through 28 days | 
| Length of ICU Stay |  | Through 28 days | 
| Duration of Ventilator Use | -For those on a ventilator at the time of randomization | Through 28 days | 
| Duration of Vasopressors Use |  | Through 28 days | 
| Duration on Renal Replacement Therapy |  | Through 28 days | 
| Viral Kinetics as Measured by Virologic Failure | -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 | Through 28 days | 
| Number of Adverse Events as Measured by CTCAE v. 5.0 |  | Through 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19