Duvelisib to Combat COVID-19

A Pilot Study of Duvelisib to Combat COVID-19

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Duvelisib; Procedure: Peripheral blood draw; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Verastem, Inc.
• Investigators: Principal Investigator: John DiPersio, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2020
• Primary Completion (Actual): February 6, 2022
• Study Completion (Actual): March 2, 2022

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 202007009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No