COVID-19
Conditions
Keywords
SARS-CoV-2
Brief summary
In this study, patients with severe coronavirus disease 2019 (COVID-19) infection will be randomized to receive duvelisib or a placebo. Participants will be enrolled at Emory University Hospital and will be identified and recruited by their treating physician and research team.
Detailed description
This randomized placebo-controlled phase 2 study will evaluate whether a two-week exposure to duvelisib, a gamma/delta phosphoinositide 3-kinase (PI3K) inhibitor, reduces inflammation in the lungs in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 who do not require mechanical ventilation at study initiation. The primary objective of the study is to determine the efficacy of duvelisib treatment in preventing death or the need for mechanical ventilation among patients with World Health Organization (WHO)-defined severe COVID-19. Key secondary endpoints will be reductions in oxygen requirements of patients and improvements in their performance status, safety and tolerability of duvelisib in the setting of COVID-19, biomarkers of inflammation, and generation of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody responses to SARS-Cov-2 spike protein. The study will determine if a two-week exposure to duvelisib beginning soon after presentation with severe COVID-19 warrants further evaluation in a larger clinical study.
Interventions
DRUGPlacebo
A placebo to match duvelisib will be taken orally twice per day for 14 days.
DRUGDuvelisib
Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.
Sponsors
Verastem, Inc.
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized in participating facility. * Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan). * Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other authorized or approved assay in any specimen collected within 72 hours prior to enrollment. Note - An exception must be requested to the Sponsor if ≥72 hours since positive test. * Symptoms suggestive of severe systemic illness with COVID-19, such as respiratory rate \> 30 breaths per minute, heart rate \>125 beats per minute, oxygen saturation (O2 sat) in the blood of \<93% on room air at sea level or the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2)\< 300 * 18 years of age or older * Patients with hematological parameters at screening consistent with \< grade 2 NCI CTCAE v5.0 toxicity: hemoglobin \>8 g/dL, platelet count \>50,000 K/mcl, an absolute neutrophil count (ANC) \>1,000/mm3, and an absolute lymphocyte count (ALC) \>500/mm3. * Patients with laboratory measurements of liver function at screening consistent with \< grade 2 NCI CTCAE v5.0 toxicity: alanine aminotransferase (ALT) \< 5 times the upper limit of normal (ULN); aspartate aminotransferase (AST) \< 5 times ULN; and bilirubin \< 3 times ULN. * The effects of duvelisib on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) must have a negative serum or urine pr5egnancy test prior to starting therapy. WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from enrollment into this study until at least 60 days after the first dose of duvelisib. A woman of childbearing potential (WOCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 2 months after completion of duvelisib administration. WOCBP must have a negative pregnancy test within 24 hours of the first dose of duvelisib. * The patient must be willing to comply with fertility requirements as below: * Total abstinence (when this is in line with the usual practice and lifestyle of the patient) will be accepted. Periodic abstinence (i.e., calendar, ovulation, post-ovulation methods) and withdrawals are not acceptable forms * If a female participant is of reproductive potential, the participant (and her partner) must agree to use of one of the following combinations of birth control during the study and for 2 months after the last dose of study drug (or tubal ligation as a single method): * Use of a double-barrier method of contraception: condoms (male or female) and a diaphragm or cervical cap with spermicide; * Use of an IUD and a barrier method: condoms (male or female, with or without spermicide) or a diaphragm or cervical cap with spermicide; * Tubal ligation. * Women who are post-menopausal, defined as age greater than 45 and no menses for at least 24 consecutive months, or who have had a hysterectomy, are considered not of reproductive potential. * Males must agree to using contraception during the study and for 2 months after the last dose of study drug or have undergone a male sterilization procedure (at least 6 months prior to screening. * Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception, or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of contraception that comparable efficacy (failure rate \<1%). In case of oral contraception, the woman should be stable on the same pill for a minimum of 3 months prior to enrollment on the study. * Patients must agree not to donate blood, sperm/ova or any other organs while taking protocol therapy and for at least 2 weeks after stopping treatment. * Willingness and ability of the patient to comply with scheduled visits, drug administration plan, protocol specified laboratory tests, other study procedures and study restrictions * Evidence of personally signed informed consent indicating that the subject is aware of the life-threatening nature of the disease and has been informed on the procedures to be followed, the experimental nature of the therapy, alternative, potential risks and discomforts, potential benefits and other pertinent aspects of study participation.
Exclusion criteria
* Patients requiring mechanical ventilation (intubation or Bi-PAP) at the time randomization. * Patients receiving any investigational drugs other than drugs or therapies to treat COVID-19, with the exception of investigational immune-modulatory drugs as per section 5.4. * Pregnant women are excluded from this study because duvelisib is agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with duvelisib, breastfeeding should be discontinued before starting study drug and breastfeeding should not be resumed until at least 1 month after last dose of study drug. * Clinical suspicion that the etiology of acute illness (acute decompensation) is primarily due to a condition other than COVID-19 * Known contraindication to duvelisib * Patients with hepatic cirrhosis as defined by symptomatic liver dysfunction; liver fibrosis by biopsy; ALT \> 5 times ULN, AST\> 5 times ULN, or bilirubin \> 3 times ULN. * Patients with autoimmune diseases or patients on chronic immunosuppressive medications at the time of hospital admission or screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requiring Mechanical Ventilation or Dying | Up to Day 29 | This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gene Expression Profile of Regulatory T Cells (Tregs) | Week 1, Week 2 | Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms. |
| Days to Recovery | Up to Day 29 | Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities. |
| Duration of Hospitalization | Up to Day 29 | The number of days spent hospitalized is presented for both study arms. |
| Days on Study Drug | Up to Day 29 | The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms. |
| Total Doses of Study Drug | Up to Day 29 | The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms. |
| Number of Participants Dying | Up to Day 29 | The incidence of death within 29 days of randomization is compared between study arms. |
| Number of Participants Transferred to ICU | Up to Day 29 | The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization. |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score | Between Day 14 and 28, Between Day 29 and 60 | The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms. |
| Number of Grade III-V Adverse Events | Up to Day 29 | The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure. |
| Number of Secondary Bacterial or Viral Infections | Up to Day 29 | The incidence of documented secondary bacterial or viral infections among participants is compared between study arms. |
| T Helper 1 (Th1) T Cell Frequency | Week 1, Week 2 | The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms. |
| Th17 T Cell Frequency | Week 1, Week 2 | The mean frequency of Th17 T cells in PBMCs is compared between study arms. |
| Interleukin-2 (IL-2) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms. |
| Interleukin-2 Receptor (IL-2R) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms. |
| Interleukin-7 (IL-7) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms. |
| Interleukin-8 (IL-8) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms. |
| Interleukin-10 (IL-10) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms. |
| Interferon Gamma-induced Protein 10 (IP-10) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IP-10is compared between study arms. |
| Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms. |
| Monocyte Chemoattractant Protein-1 (MCP-1) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms. |
| Granulocyte Colony-stimulating Factor (G-CSF) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms. |
| Tumor Necrosis Factor (TNF)-Alpha Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms. |
| Gene Expression Profile of Cluster of Differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)+ | Week 1, Week 2 | Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms. |
| Gene Expression Profile of CD8+ T Cell Immunoglobulin and Mucin Domain-containing Protein 3 (Tim3)+ Programmed Cell Death Protein 1 (PD-1)+ | Week 1, Week 2 | Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms. |
| Gene Expression Profile of Cluster of Differentiation 14 (CD14)+ Cluster of Differentiation (CD16)+ Monocytes | Week 1, Week 2 | Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms. |
| Immunoglobin G (IgG) Antibodies | Week 4 | Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms. |
| Number of Participants Surviving | Up to Day 60 | Overall survival is defined as days from randomization to death and censored at last follow up. |
| Interleukin-6 (IL-6) Levels | Week 1, Week 2 | Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Vasoactive Intestinal Peptide (VIP) | Week 1, Week 2 | VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at Emory University Hospital in Atlanta, Georgia, USA. Participant enrollment began November 18, 2020 and all follow-up assessments were completed by June 10, 2021.
Participants by arm
| Arm | Count |
|---|---|
| Duvelisib Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days. | 25 |
| Placebo Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days. | 22 |
| Total | 47 |
Baseline characteristics
| Characteristic | Placebo | Total | Duvelisib |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 14 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 33 Participants | 18 Participants |
| Age, Continuous | 58.9 years STANDARD_DEVIATION 17.1 | 57.4 years STANDARD_DEVIATION 14.6 | 56.1 years STANDARD_DEVIATION 12.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 29 Participants | 17 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment United States | 22 Participants | 47 Participants | 25 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 26 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 1 / 22 |
| other Total, other adverse events | 5 / 25 | 5 / 22 |
| serious Total, serious adverse events | 6 / 25 | 2 / 22 |
Outcome results
Primary
Number of Participants Requiring Mechanical Ventilation or Dying
This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.
Time frame: Up to Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib | Number of Participants Requiring Mechanical Ventilation or Dying | 3 Participants |
| Placebo | Number of Participants Requiring Mechanical Ventilation or Dying | 3 Participants |
Secondary
Days on Study Drug
The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms.
Time frame: Up to Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duvelisib | Days on Study Drug | 4.6 days | Standard Deviation 3.55 |
| Placebo | Days on Study Drug | 5.18 days | Standard Deviation 2.77 |
Secondary
Days to Recovery
Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities.
Time frame: Up to Day 29
Population: This analysis includes participants who recovered; one participant in the placebo study arm passed away and is not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duvelisib | Days to Recovery | 6.00 days | Standard Deviation 6.19 |
| Placebo | Days to Recovery | 5.29 days | Standard Deviation 4.19 |
Secondary
Duration of Hospitalization
The number of days spent hospitalized is presented for both study arms.
Time frame: Up to Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duvelisib | Duration of Hospitalization | 6.72 days | Standard Deviation 7.48 |
| Placebo | Duration of Hospitalization | 6.95 days | Standard Deviation 6.41 |
Secondary
Eastern Cooperative Oncology Group (ECOG) Performance Status Score
The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms.
Time frame: Between Day 14 and 28, Between Day 29 and 60
Population: This analysis includes participants who were able to be contacted for this assessment, or those with relevant information in the medical chart.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Eastern Cooperative Oncology Group (ECOG) Performance Status Score | Single assessment between Day 14 and 28 | 2 score on a scale | Standard Deviation 1.01 |
| Duvelisib | Eastern Cooperative Oncology Group (ECOG) Performance Status Score | Single assessment between Day 29 and 60 | 1 score on a scale | Standard Deviation 0.69 |
| Placebo | Eastern Cooperative Oncology Group (ECOG) Performance Status Score | Single assessment between Day 14 and 28 | 1.5 score on a scale | Standard Deviation 1.04 |
| Placebo | Eastern Cooperative Oncology Group (ECOG) Performance Status Score | Single assessment between Day 29 and 60 | 1 score on a scale | Standard Deviation 1.04 |
Secondary
Gene Expression Profile of CD8+ T Cell Immunoglobulin and Mucin Domain-containing Protein 3 (Tim3)+ Programmed Cell Death Protein 1 (PD-1)+
Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.
Time frame: Week 1, Week 2
Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.
Secondary
Gene Expression Profile of Cluster of Differentiation 14 (CD14)+ Cluster of Differentiation (CD16)+ Monocytes
Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms.
Time frame: Week 1, Week 2
Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.
Secondary
Gene Expression Profile of Cluster of Differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)+
Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.
Time frame: Week 1, Week 2
Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.
Secondary
Gene Expression Profile of Regulatory T Cells (Tregs)
Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms.
Time frame: Week 1, Week 2
Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.
Secondary
Granulocyte Colony-stimulating Factor (G-CSF) Levels
Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Granulocyte Colony-stimulating Factor (G-CSF) Levels | Week 1 | 8.1585 pg/mL | Standard Deviation 42.8679 |
| Duvelisib | Granulocyte Colony-stimulating Factor (G-CSF) Levels | Week 2 | 8.6447 pg/mL | Standard Deviation 78.3263 |
| Placebo | Granulocyte Colony-stimulating Factor (G-CSF) Levels | Week 1 | 157.86 pg/mL | Standard Deviation 43.5125 |
| Placebo | Granulocyte Colony-stimulating Factor (G-CSF) Levels | Week 2 | 39.7275 pg/mL | Standard Deviation 97.289 |
Secondary
Immunoglobin G (IgG) Antibodies
Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms.
Time frame: Week 4
Population: Due to budget limitations other laboratory experiments were prioritized and Immunoglobulin G (IgG) antibodies were not measured.
Secondary
Interferon Gamma-induced Protein 10 (IP-10) Levels
Mean levels of the inflammatory serum biomarker IP-10is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interferon Gamma-induced Protein 10 (IP-10) Levels | Week 1 | 3136.50 pg/mL | Standard Deviation 652.84 |
| Duvelisib | Interferon Gamma-induced Protein 10 (IP-10) Levels | Week 2 | 2956.68 pg/mL | Standard Deviation 1122.8 |
| Placebo | Interferon Gamma-induced Protein 10 (IP-10) Levels | Week 1 | 4781.42 pg/mL | Standard Deviation 649.35 |
| Placebo | Interferon Gamma-induced Protein 10 (IP-10) Levels | Week 2 | 3809.83 pg/mL | Standard Deviation 1442.4 |
Secondary
Interleukin-10 (IL-10) Levels
Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interleukin-10 (IL-10) Levels | Week 2 | 658.17 pg/mL | Standard Deviation 1411.11 |
| Duvelisib | Interleukin-10 (IL-10) Levels | Week 1 | 389.02 pg/mL | Standard Deviation 838.5 |
| Placebo | Interleukin-10 (IL-10) Levels | Week 2 | 250.00 pg/mL | Standard Deviation 1836.14 |
| Placebo | Interleukin-10 (IL-10) Levels | Week 1 | 808.09 pg/mL | Standard Deviation 831.24 |
Secondary
Interleukin-2 (IL-2) Levels
Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interleukin-2 (IL-2) Levels | Week 1 | 0.08723 pg/mL | Standard Deviation 18.065 |
| Duvelisib | Interleukin-2 (IL-2) Levels | Week 2 | 17.3632 pg/mL | Standard Deviation 40.588 |
| Placebo | Interleukin-2 (IL-2) Levels | Week 1 | 62.8596 pg/mL | Standard Deviation 18.171 |
| Placebo | Interleukin-2 (IL-2) Levels | Week 2 | 0.3158 pg/mL | Standard Deviation 32.3258 |
Secondary
Interleukin-2 Receptor (IL-2R) Levels
Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interleukin-2 Receptor (IL-2R) Levels | Week 1 | 1172.80 pg/mL | Standard Deviation 529.75 |
| Duvelisib | Interleukin-2 Receptor (IL-2R) Levels | Week 2 | 912.47 pg/mL | Standard Deviation 976.08 |
| Placebo | Interleukin-2 Receptor (IL-2R) Levels | Week 1 | 3569.93 pg/mL | Standard Deviation 540.08 |
| Placebo | Interleukin-2 Receptor (IL-2R) Levels | Week 2 | 2005.94 pg/mL | Standard Deviation 1207.7 |
Secondary
Interleukin-6 (IL-6) Levels
Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interleukin-6 (IL-6) Levels | Week 1 | 7.9388 pg/mL | Standard Deviation 41.3498 |
| Duvelisib | Interleukin-6 (IL-6) Levels | Week 2 | 14.2294 pg/mL | Standard Deviation 75.829 |
| Placebo | Interleukin-6 (IL-6) Levels | Week 2 | 52.2227 pg/mL | Standard Deviation 94.026 |
| Placebo | Interleukin-6 (IL-6) Levels | Week 1 | 149.73 pg/mL | Standard Deviation 42.0497 |
Secondary
Interleukin-7 (IL-7) Levels
Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interleukin-7 (IL-7) Levels | Week 1 | 4.6018 pg/mL | Standard Deviation 54.6831 |
| Duvelisib | Interleukin-7 (IL-7) Levels | Week 2 | 3.2255 pg/mL | Standard Deviation 98.8781 |
| Placebo | Interleukin-7 (IL-7) Levels | Week 1 | 198.80 pg/mL | Standard Deviation 55.2375 |
| Placebo | Interleukin-7 (IL-7) Levels | Week 2 | 48.5118 pg/mL | Standard Deviation 123.46 |
Secondary
Interleukin-8 (IL-8) Levels
Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Interleukin-8 (IL-8) Levels | Week 1 | 3.1109 pg/mL | Standard Deviation 28.2498 |
| Duvelisib | Interleukin-8 (IL-8) Levels | Week 2 | 3.4120 pg/mL | Standard Deviation 51.3241 |
| Placebo | Interleukin-8 (IL-8) Levels | Week 1 | 104.03 pg/mL | Standard Deviation 28.5967 |
| Placebo | Interleukin-8 (IL-8) Levels | Week 2 | 26.6383 pg/mL | Standard Deviation 63.927 |
Secondary
Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels
Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels | Week 1 | 29.0477 pg/mL | Standard Deviation 26.449 |
| Duvelisib | Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels | Week 2 | 43.0115 pg/mL | Standard Deviation 48.356 |
| Placebo | Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels | Week 1 | 123.60 pg/mL | Standard Deviation 26.855 |
| Placebo | Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels | Week 2 | 57.5810 pg/mL | Standard Deviation 60.045 |
Secondary
Monocyte Chemoattractant Protein-1 (MCP-1) Levels
Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Monocyte Chemoattractant Protein-1 (MCP-1) Levels | Week 1 | 122.63 pg/mL | Standard Deviation 28.2616 |
| Duvelisib | Monocyte Chemoattractant Protein-1 (MCP-1) Levels | Week 2 | 255.30 pg/mL | Standard Deviation 46.5051 |
| Placebo | Monocyte Chemoattractant Protein-1 (MCP-1) Levels | Week 1 | 124.80 pg/mL | Standard Deviation 27.9714 |
| Placebo | Monocyte Chemoattractant Protein-1 (MCP-1) Levels | Week 2 | 187.12 pg/mL | Standard Deviation 61.2899 |
Secondary
Number of Grade III-V Adverse Events
The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure.
Time frame: Up to Day 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib | Number of Grade III-V Adverse Events | 6 grade III-V adverse events |
| Placebo | Number of Grade III-V Adverse Events | 3 grade III-V adverse events |
Secondary
Number of Participants Dying
The incidence of death within 29 days of randomization is compared between study arms.
Time frame: Up to Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib | Number of Participants Dying | 0 Participants |
| Placebo | Number of Participants Dying | 1 Participants |
Secondary
Number of Participants Surviving
Overall survival is defined as days from randomization to death and censored at last follow up.
Time frame: Up to Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib | Number of Participants Surviving | 25 Participants |
| Placebo | Number of Participants Surviving | 21 Participants |
Secondary
Number of Participants Transferred to ICU
The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization.
Time frame: Up to Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib | Number of Participants Transferred to ICU | 3 Participants |
| Placebo | Number of Participants Transferred to ICU | 3 Participants |
Secondary
Number of Secondary Bacterial or Viral Infections
The incidence of documented secondary bacterial or viral infections among participants is compared between study arms.
Time frame: Up to Day 29
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duvelisib | Number of Secondary Bacterial or Viral Infections | Count of bacterial infections | 0 infections |
| Duvelisib | Number of Secondary Bacterial or Viral Infections | Count of viral infections | 0 infections |
| Placebo | Number of Secondary Bacterial or Viral Infections | Count of bacterial infections | 1 infections |
| Placebo | Number of Secondary Bacterial or Viral Infections | Count of viral infections | 0 infections |
Secondary
Th17 T Cell Frequency
The mean frequency of Th17 T cells in PBMCs is compared between study arms.
Time frame: Week 1, Week 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Th17 T Cell Frequency | Week 1 | 2.24 percentage of CD4 T cells | Standard Deviation 4.65 |
| Duvelisib | Th17 T Cell Frequency | Week 2 | 3.16 percentage of CD4 T cells | Standard Deviation 2.44 |
| Placebo | Th17 T Cell Frequency | Week 2 | 4.25 percentage of CD4 T cells | Standard Deviation 3.21 |
| Placebo | Th17 T Cell Frequency | Week 1 | 3.43 percentage of CD4 T cells | Standard Deviation 3.78 |
Secondary
T Helper 1 (Th1) T Cell Frequency
The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms.
Time frame: Week 1, Week 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | T Helper 1 (Th1) T Cell Frequency | Week 1 | 19.52 percentage of CD4 T cells | Standard Deviation 4.77 |
| Duvelisib | T Helper 1 (Th1) T Cell Frequency | Week 2 | 19.98 percentage of CD4 T cells | Standard Deviation 6.24 |
| Placebo | T Helper 1 (Th1) T Cell Frequency | Week 1 | 20.14 percentage of CD4 T cells | Standard Deviation 7.52 |
| Placebo | T Helper 1 (Th1) T Cell Frequency | Week 2 | 18.27 percentage of CD4 T cells | Standard Deviation 6.8 |
Secondary
Total Doses of Study Drug
The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms.
Time frame: Up to Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duvelisib | Total Doses of Study Drug | 7.76 drug doses | Standard Deviation 6.79 |
| Placebo | Total Doses of Study Drug | 8.91 drug doses | Standard Deviation 5.61 |
Secondary
Tumor Necrosis Factor (TNF)-Alpha Levels
Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms.
Time frame: Week 1, Week 2
Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib | Tumor Necrosis Factor (TNF)-Alpha Levels | Week 2 | 2.6108 pg/mL | Standard Deviation 40.1411 |
| Duvelisib | Tumor Necrosis Factor (TNF)-Alpha Levels | Week 1 | 1.3291 pg/mL | Standard Deviation 21.8406 |
| Placebo | Tumor Necrosis Factor (TNF)-Alpha Levels | Week 1 | 81.0170 pg/mL | Standard Deviation 22.236 |
| Placebo | Tumor Necrosis Factor (TNF)-Alpha Levels | Week 2 | 17.0332 pg/mL | Standard Deviation 49.723 |
Other Pre-specified
Vasoactive Intestinal Peptide (VIP)
VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.
Time frame: Week 1, Week 2
Population: Due to budget limitations other laboratory experiments were prioritized and VIP (an exploratory outcome) was not analyzed.