Duvelisib to Combat COVID-19
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Duvelisib
Peripheral blood draw
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19
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.
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Duvelisib
Placebo
Arm Description
-Duvelisib 25 mg twice daily for up to 10 days.
-Placebo 25 mg twice daily for up to 10 days.
Outcomes
Primary Outcome Measures
Overall Survival as Measured by Number of Participants Alive Through 28 Days
Secondary Outcome Measures
Length of Hospital Stay
Length of ICU Stay
Duration of Ventilator Use
-For those on a ventilator at the time of randomization
Duration of Vasopressors Use
Duration on Renal Replacement Therapy
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
Number of Adverse Events as Measured by CTCAE v. 5.0
Full Information
NCT ID
NCT04372602
First Posted
April 30, 2020
Last Updated
March 2, 2023
Sponsor
Washington University School of Medicine
Collaborators
Verastem, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04372602
Brief Title
Duvelisib to Combat COVID-19
Official Title
A Pilot Study of Duvelisib to Combat COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
October 12, 2020 (Actual)
Primary Completion Date
February 6, 2022 (Actual)
Study Completion Date
March 2, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Verastem, Inc.
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Blocks of 10 patients will be used to allocate patients to duvelisib or placebo
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Duvelisib
Arm Type
Experimental
Arm Description
-Duvelisib 25 mg twice daily for up to 10 days.
Arm Title
Placebo
Arm Type
Sham Comparator
Arm Description
-Placebo 25 mg twice daily for up to 10 days.
Intervention Type
Drug
Intervention Name(s)
Duvelisib
Other Intervention Name(s)
Copiktra
Intervention Description
-For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.
Intervention Type
Procedure
Intervention Name(s)
Peripheral blood draw
Intervention Description
First 10 patients enrolled
Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
-Provided by Verastem
Primary Outcome Measure Information:
Title
Overall Survival as Measured by Number of Participants Alive Through 28 Days
Time Frame
Through 28 days
Secondary Outcome Measure Information:
Title
Length of Hospital Stay
Time Frame
Through 28 days
Title
Length of ICU Stay
Time Frame
Through 28 days
Title
Duration of Ventilator Use
Description
-For those on a ventilator at the time of randomization
Time Frame
Through 28 days
Title
Duration of Vasopressors Use
Time Frame
Through 28 days
Title
Duration on Renal Replacement Therapy
Time Frame
Through 28 days
Title
Viral Kinetics as Measured by Virologic Failure
Description
-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
Time Frame
Through 28 days
Title
Number of Adverse Events as Measured by CTCAE v. 5.0
Time Frame
Through 29 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John DiPersio, M.D., Ph.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Duvelisib to Combat COVID-19
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