COVID-19
Conditions
Keywords
COVID-19
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.
Interventions
DRUGDuvelisib
-For patients unable to administer orally, a duvelisib suspension will be administered through a nasogastric/orogastric tube.
PROCEDUREPeripheral blood draw
* First 10 patients enrolled * Screening, Day 2, Day 4, Day 8, Day 10, Day 15, and Day 29
DRUGPlacebo
-Provided by Verastem
Sponsors
Verastem, Inc.
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Blocks of 10 patients will be used to allocate patients to duvelisib or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival as Measured by Number of Participants Alive Through 28 Days | Through 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of ICU 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 | — |
| Length of Hospital Stay | 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 |
| Number of Adverse Events as Measured by CTCAE v. 5.0 | Through 29 days | — |
| Duration on Renal Replacement Therapy | Through 28 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duvelisib -Duvelisib 25 mg twice daily for up to 10 days. | 15 |
| Placebo -Placebo 25 mg twice daily for up to 10 days. | 13 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Transitioned to comfort care | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Duvelisib | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 63 years | 63 years | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 28 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 17 Participants | 8 Participants |
| Region of Enrollment United States | 15 participants | 28 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 17 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 15 | 8 / 13 |
| other Total, other adverse events | 15 / 15 | 13 / 13 |
| serious Total, serious adverse events | 6 / 15 | 8 / 13 |
Outcome results
Primary
Overall Survival as Measured by Number of Participants Alive Through 28 Days
Time frame: Through 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib | Overall Survival as Measured by Number of Participants Alive Through 28 Days | 10 Participants |
| Placebo | Overall Survival as Measured by Number of Participants Alive Through 28 Days | 8 Participants |
Secondary
Duration of Vasopressors Use
Time frame: Through 28 days
Population: 12 participants were not evaluable in the duvelisib arm as the participants did not receive vasopressors. 8 participants were not evaluable in the placebo arm as the participants did not receive vasopressors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib | Duration of Vasopressors Use | 9 days |
| Placebo | Duration of Vasopressors Use | 19 days |
Secondary
Duration of Ventilator Use
-For those on a ventilator at the time of randomization
Time frame: Through 28 days
Population: 6 participants were not evaluable in the duvelisib arm as the participants were not on ventilators. 4 participants were not evaluable in the placebo arm as the participants were not on ventilators.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib | Duration of Ventilator Use | 16 days |
| Placebo | Duration of Ventilator Use | 20 days |
Secondary
Duration on Renal Replacement Therapy
Time frame: Through 28 days
Population: 14 participants were not evaluable in the duvelisib arm as the participants did not receive renal replacement therapy. 9 participants were not evaluable in the placebo arm as the participants did not receive renal replacement therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib | Duration on Renal Replacement Therapy | 28 days |
| Placebo | Duration on Renal Replacement Therapy | 19 days |
Secondary
Length of Hospital Stay
Time frame: Through 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib | Length of Hospital Stay | 19 days |
| Placebo | Length of Hospital Stay | 24 days |
Secondary
Length of ICU Stay
Time frame: Through 28 days
Population: 1 participant was not evaluable in the placebo arm as the participant was not in the ICU.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib | Length of ICU Stay | 19 days |
| Placebo | Length of ICU Stay | 20.50 days |
Secondary
Number of Adverse Events as Measured by CTCAE v. 5.0
Time frame: Through 29 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 conjunctivitis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 sinus tachycardia | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 ventricular arrhythmia | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 ileus | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 lower gastrointestinal hemorrhage | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 melena | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 fever | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypothermia | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 cholecystitis | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 acidosis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 acidosis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypercalcemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hyperkalemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypotension | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 sinus bradycardia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 anemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 anemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 leukocytosis | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 atrial fibrillation | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 cardiac arrest | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 pericarditis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 middle ear inflammation | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypernatremia | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 corneal ulcer | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 colitis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 constipation | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 diarrhea | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 gastroparesis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 mucositis oral | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 oral hemorrhage | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 pancreatitis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 rectal ulcer | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 upper gastrointestinal hemorrhage | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 vomiting | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 vomiting | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 fever | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 bacteremia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 conjunctivitis infective | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 lung infection | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 lung infection | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 sepsis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 sinusitis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 tracheitis | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 tracheitis | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 urinary tract infection | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 urinary tract infection | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 alanine aminotransferase increased | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 alkaline phosphatase increased | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 aspartate aminotransferase increased | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 blood bilirubin increased | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 elevated LFT NOS | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 platelet count decreased | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyperglycemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyperkalemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypernatremia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyperphosphatemia | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypoalbuminemia | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyponatremia | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 arthritis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 intracranial hemorrhage | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 stroke | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 syncope | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 delirium | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 acute kidney injury | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 acute kidney injury | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hematuria | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hematoma | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hematuria | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 cough | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 epistaxis | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 epistaxis | 2 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypoxia | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 pharyngeal hemorrhage | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 pneumothorax | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 respiratory failure | 6 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 moisture associated skin damage | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 pressure ulcer | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 rash acneiform | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 skin tear | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 skin ulceration | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 subcutaneous emphysema | 1 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypotension | 3 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 peripheral ischemia | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 thromboembolic event | 0 Participants |
| Duvelisib | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 thromboembolic event | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 subcutaneous emphysema | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypernatremia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 arthritis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 sinus bradycardia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 tracheitis | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 sinus tachycardia | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 acute kidney injury | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 gastroparesis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 urinary tract infection | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 ileus | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 moisture associated skin damage | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 urinary tract infection | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypotension | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 fever | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 alanine aminotransferase increased | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypothermia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hematuria | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 alkaline phosphatase increased | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 acidosis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 pressure ulcer | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 acidosis | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 aspartate aminotransferase increased | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hematuria | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hyperkalemia | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 blood bilirubin increased | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 sinusitis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 thromboembolic event | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 elevated LFT NOS | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 anemia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 cough | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 anemia | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 platelet count decreased | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 leukocytosis | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypercalcemia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 atrial fibrillation | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 rash acneiform | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 cardiac arrest | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyperglycemia | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 pericarditis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 ventricular arrhythmia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 epistaxis | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 middle ear inflammation | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyperkalemia | 3 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 conjunctivitis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 epistaxis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 corneal ulcer | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypotension | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 colitis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypernatremia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 constipation | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hematoma | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 diarrhea | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyperphosphatemia | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 lower gastrointestinal hemorrhage | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 melena | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 skin tear | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 mucositis oral | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hypoalbuminemia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 oral hemorrhage | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 hypoxia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 pancreatitis | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 hyponatremia | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 rectal ulcer | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 thromboembolic event | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 upper gastrointestinal hemorrhage | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 pharyngeal hemorrhage | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 vomiting | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 intracranial hemorrhage | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 vomiting | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 skin ulceration | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 fever | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 cholecystitis | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 stroke | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 bacteremia | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 pneumothorax | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 conjunctivitis infective | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 syncope | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 lung infection | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 peripheral ischemia | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 lung infection | 4 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 delirium | 1 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 sepsis | 2 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 3/4/5 respiratory failure | 5 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 acute kidney injury | 0 Participants |
| Placebo | Number of Adverse Events as Measured by CTCAE v. 5.0 | Grade 1/2 tracheitis | 1 Participants |
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
Time frame: Through 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib | Viral Kinetics as Measured by Virologic Failure | 3 Participants |
| Placebo | Viral Kinetics as Measured by Virologic Failure | 5 Participants |