Brief Summary
CALAVI will investigate the safety, efficacy and pharmacokinetics of acalabrutinib together with Best Supportive Care in the treatment of COVID-19.
Brief Title
Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.
Categories
Completion Date
Completion Date Type
Actual
Conditions
COVID-19
Eligibility Criteria
Inclusion Criteria:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent or have a legal representative provide consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)
2. Men and women ≥18 years of age at the time of signing the informed consent form
3. Confirmed infection with SARS-CoV-2 confirmed per World Health Organization (WHO) criteria (including positive RT-PCR nucleic acid test of any specimen \[eg, respiratory, blood, urine, stool, or other bodily fluid\]) within 4 days of randomization
4. COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation \<94% on room air or requires supplemental oxygen
5. Able to swallow pills
6. Willing to follow contraception guidelines
Exclusion Criteria:
1. Respiratory failure at time of screening due to COVID-19
2. Known medical resuscitation within 14 days of randomization
3. Pregnant or breast feeding
4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARS-CoV-2)
5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin ≥ 3x upper limit of normal (ULN) and/or severe hepatic impairment detected within 24 hours at screening (per local lab)
6. Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll
7. Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug).
8. Requires treatment with proton-pump inhibitors (PPIs; eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving PPIs who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study
9. Received oral antirejection or immunomodulatory drugs (eg, anticytokines, Btk inhibitors, JAK inhibitors, PI3K inhibitors) within 30 days before randomization on study
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent or have a legal representative provide consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)
2. Men and women ≥18 years of age at the time of signing the informed consent form
3. Confirmed infection with SARS-CoV-2 confirmed per World Health Organization (WHO) criteria (including positive RT-PCR nucleic acid test of any specimen \[eg, respiratory, blood, urine, stool, or other bodily fluid\]) within 4 days of randomization
4. COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation \<94% on room air or requires supplemental oxygen
5. Able to swallow pills
6. Willing to follow contraception guidelines
Exclusion Criteria:
1. Respiratory failure at time of screening due to COVID-19
2. Known medical resuscitation within 14 days of randomization
3. Pregnant or breast feeding
4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARS-CoV-2)
5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin ≥ 3x upper limit of normal (ULN) and/or severe hepatic impairment detected within 24 hours at screening (per local lab)
6. Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll
7. Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug).
8. Requires treatment with proton-pump inhibitors (PPIs; eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving PPIs who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study
9. Received oral antirejection or immunomodulatory drugs (eg, anticytokines, Btk inhibitors, JAK inhibitors, PI3K inhibitors) within 30 days before randomization on study
Inclusion Criteria
Inclusion Criteria:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent or have a legal representative provide consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)
2. Men and women ≥18 years of age at the time of signing the informed consent form
3. Confirmed infection with SARS-CoV-2 confirmed per World Health Organization (WHO) criteria (including positive RT-PCR nucleic acid test of any specimen \[eg, respiratory, blood, urine, stool, or other bodily fluid\]) within 4 days of randomization
4. COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation \<94% on room air or requires supplemental oxygen
5. Able to swallow pills
6. Willing to follow contraception guidelines
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent or have a legal representative provide consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)
2. Men and women ≥18 years of age at the time of signing the informed consent form
3. Confirmed infection with SARS-CoV-2 confirmed per World Health Organization (WHO) criteria (including positive RT-PCR nucleic acid test of any specimen \[eg, respiratory, blood, urine, stool, or other bodily fluid\]) within 4 days of randomization
4. COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation \<94% on room air or requires supplemental oxygen
5. Able to swallow pills
6. Willing to follow contraception guidelines
Gender
All
Gender Based
false
Keywords
2019 novel coronavirus disease
Acalabrutinib
Btk inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
130 Years
Minimum Age
18 Years
NCT Id
NCT04346199
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D822FC00001
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2, Open Label, Randomized Study of the Efficacy and Safety of Acalabrutinib With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19
Primary Outcomes
Outcome Description
Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Outcome Measure
Percentage of Participants Alive and Free of Respiratory Failure at Day 14
Outcome Time Frame
At Day 14
Secondary Outcomes
Outcome Time Frame
Screening to 28 (+3) days after last dose of acalabrutinib (for acalabrutinib + BSC participants) or to 38 (+3) days after randomization (for BSC alone participants)
Outcome Measure
Number of Participants With Adverse Events and Serious Adverse Events
Outcome Description
Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by highflow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Outcome Time Frame
At Day 28
Outcome Measure
Percentage of Participants Alive and Free of Respiratory Failure at Day 28
Outcome Description
Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Outcome Time Frame
Days 3, 5, 7, 10, 14, 28
Outcome Measure
Percent Change From Baseline in C-reactive Protein.
Outcome Description
Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Outcome Time Frame
Days 3, 5, 7, 10, 14, 28
Outcome Measure
Percent Change From Baseline in Ferritin
Outcome Description
Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Outcome Time Frame
Days 3, 5, 7, 10, 14, 28
Outcome Measure
Percent Change From Baseline in Absolute Lymphocyte Count
Outcome Description
Median overall survival, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.
Outcome Time Frame
From randomization until 90 days after randomization. Safety Issue:
Outcome Measure
Overall Survival
Outcome Time Frame
At Day 14 and at Day 28
Outcome Measure
Percentage of Participants Alive and Discharged From ICU
Outcome Description
Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.
Outcome Time Frame
From randomization to 28 days after randomization.
Outcome Measure
Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause
Outcome Description
Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by highflow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Outcome Time Frame
From randomization to 28 days after randomization.
Outcome Measure
Number of Days Alive and Free of Respiratory Failure
Outcome Description
Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days with respiratory failure. For participants in hospital and experiencing respiratory failure at the time they withdraw from the study, days from last known status to Day 28 are counted as days with respiratory failure.
Outcome Time Frame
From randomization to 28 days after randomization.
Outcome Measure
Number of Days With Respiratory Failure
Outcome Description
For this summary, the hospitalization must be considered clinically indicated to count as a day hospitalized.
For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days hospitalized.
For participants in hospital at the time they withdraw from the study, days from last known status to Day 28 are counted as days hospitalized.
For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days hospitalized.
For participants in hospital at the time they withdraw from the study, days from last known status to Day 28 are counted as days hospitalized.
Outcome Time Frame
From randomization to 28 days after randomization.
Outcome Measure
Number of Days Hospitalized
Outcome Description
For this summary, the ICU stay must be considered clinically indicated to count as a day in ICU.
For participants who die (due to any cause) prior to Day 90, days from death to Day 90 are counted as days in ICU.
For participants who die (due to any cause) prior to Day 90, days from death to Day 90 are counted as days in ICU.
Outcome Time Frame
From randomization to 90 days after randomization.
Outcome Measure
Number of Days in ICU
Outcome Time Frame
From randomization to 28 days after randomization.
Outcome Measure
Number of Days Alive Outside of Hospital
Outcome Time Frame
From randomization to 90 days after randomization.
Outcome Measure
Number of Days Alive Outside of Hospital
Outcome Description
Baseline is defined as the result obtained on the date of randomization.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.
The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.
Outcome Time Frame
Days 3, 5, 7, 10, 14, 28
Outcome Measure
Percent Change From Baseline in Oxygenation Index
Outcome Description
9-point category ordinal scale: 0. \* Uninfected, no clinical or virological evidence of infection
1. Ambulatory, no limitation of activities
2. Ambulatory, limitation of activities
3. Hospitalized - mild disease, no oxygen therapy
4. Hospitalized - mild disease, oxygen by mask or nasal prongs
5. Hospitalized - severe disease, non-invasive ventilation or high flow oxygen
6. Hospitalised - severe disease, intubation and mechanical ventilation
7. Hospitalized - severe disease, ventilation and additional organ support, such as pressors, renal replacement therapy, extracorporeal membrane oxygenation
8. Death
Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.
1. Ambulatory, no limitation of activities
2. Ambulatory, limitation of activities
3. Hospitalized - mild disease, no oxygen therapy
4. Hospitalized - mild disease, oxygen by mask or nasal prongs
5. Hospitalized - severe disease, non-invasive ventilation or high flow oxygen
6. Hospitalised - severe disease, intubation and mechanical ventilation
7. Hospitalized - severe disease, ventilation and additional organ support, such as pressors, renal replacement therapy, extracorporeal membrane oxygenation
8. Death
Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.
Outcome Time Frame
From randomization to 28 days after randomization.
Outcome Measure
Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale
Outcome Description
Summary of plasma concentrations (ng/mL) of acalabrutinib
Outcome Time Frame
Day 3 and Day 7
Outcome Measure
Pharmacokinetics of Acalabrutinib
Outcome Description
Summary of plasma concentrations (ng/mL) of ACP-5862
Outcome Time Frame
Day 3 and Day 7
Outcome Measure
Pharmacokinetics of ACP-5862
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
130
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Noah Kornblum
Investigator Email
nkornblu@montefiore.org
Investigator Phone
718-920-4826