Duvelisib to Combat COVID-19

COVID-19 Clinical Trial

Official title:

A Pilot Study of Duvelisib to Combat COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04372602
• Other study ID #: 202007009
• Status: Completed
• Phase: Phase 2
• Start date: October 12, 2020
• Est. completion date: March 2, 2022

Study information

• Verified date: March 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: March 2, 2022
• Est. primary completion date: February 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Duvelisib
-For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.

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

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Verastem, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival as Measured by Number of Participants Alive Through 28 Days		Through 28 days
Secondary	Length of Hospital Stay		Through 28 days
Secondary	Length of ICU Stay		Through 28 days
Secondary	Duration of Ventilator Use	-For those on a ventilator at the time of randomization	Through 28 days
Secondary	Duration of Vasopressors Use		Through 28 days
Secondary	Duration on Renal Replacement Therapy		Through 28 days
Secondary	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
Secondary	Number of Adverse Events as Measured by CTCAE v. 5.0		Through 29 days

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine