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Trial record 2 of 6 for:    Acalabrutinib | Covid19

Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19. (CALAVI US)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04380688
Recruitment Status : Completed
First Posted : May 8, 2020
Results First Posted : September 13, 2021
Last Update Posted : September 13, 2021
Sponsor:
Collaborator:
Acerta Pharma BV
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition COVID-19
Intervention Drug: Acalabrutinib
Enrollment 62
Recruitment Details All participants were recruited from the United States and had COVID-19 pneumonia (documented radiographically) requiring hospitalization. The first participant was randomized on 13 June 2020 and the last participant was randomized on 20 August 2020.
Pre-assignment Details Screening assessments were performed within the 3 days prior to randomization. Of 70 screened participants, 62 were enrolled. Of the 8 participants that were not enrolled, 7 were screen failures (did not meet eligibility criteria) and 1 withdrew consent.
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines. Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Period Title: Overall Study
Started 31 31
Completed 24 22
Not Completed 7 9
Reason Not Completed
Death             2             2
Lost to Follow-up             2             4
Withdrawal by Subject             3             3
Arm/Group Title Acalabrutinib + BSC BSC Alone Total
Hide Arm/Group Description Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines. Participants received best supportive care per the discretion of the Investigator and institutional guidelines. Total of all reporting groups
Overall Number of Baseline Participants 31 31 62
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 31 participants 62 participants
52.5  (13.3) 51.9  (14.3) 52.2  (13.7)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 31 participants 31 participants 62 participants
< 65 years 26 25 51
>= 65 years 5 6 11
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 31 participants 62 participants
Female
13
  41.9%
9
  29.0%
22
  35.5%
Male
18
  58.1%
22
  71.0%
40
  64.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 31 participants 31 participants 62 participants
HISPANIC OR LATINO 15 13 28
NOT HISPANIC OR LATINO 16 17 33
NOT REPORTED 0 0 0
MISSING 0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 31 participants 31 participants 62 participants
WHITE 18 20 38
BLACK OR AFRICAN AMERICAN 7 5 12
AMERICAN INDIAN OR ALASKA NATIVE 1 0 1
ASIAN 0 0 0
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 0 0 0
OTHER 3 2 5
NOT REPORTED 2 3 5
MISSING 0 1 1
1.Primary Outcome
Title Number of Participants With Adverse Events and Serious Adverse Events
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide Analysis Population Description

Safety analysis set: If the participant receives at least 1 dose of acalabrutinib, they are summarized in the Acalabrutinib + BSC group. Otherwise, they are summarized in the BSC alone group.

The number of participants in the BSC alone group (32) is greater than the number of participants randomized to this group (31) because one participant randomized to Acalabrutinib + BSC did not receive any acalabrutinib and therefore is included in the BSC alone group for the safety analysis set.

Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 30 32
Measure Type: Count of Participants
Unit of Measure: Participants
Any Adverse Event
17
  56.7%
15
  46.9%
Any Serious Adverse Event
4
  13.3%
6
  18.8%
2.Primary Outcome
Title Percentage of Participants Alive and Free of Respiratory Failure at Day 28
Hide 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) Noninvasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Time Frame At Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
80.6
(67.4 to 93.9)
83.9
(71.4 to 96.3)
3.Secondary Outcome
Title Percentage of Participants Alive and Free of Respiratory Failure at Day 14
Hide 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) Noninvasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Time Frame At Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
80.6
(67.4 to 93.9)
87.1
(75.6 to 98.6)
4.Secondary Outcome
Title Percent Change From Baseline in C-reactive Protein.
Hide 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.

Time Frame Days 3, 5, 7, 10, 14, 28
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 27 participants 24 participants
-41.08  (71.27) -26.74  (69.02)
Day 5 Number Analyzed 18 participants 18 participants
-72.05  (26.29) -49.55  (54.97)
Day 7 Number Analyzed 11 participants 12 participants
-75.72  (29.48) -40.53  (75.99)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 30 participants 29 participants
-73.85  (27.92) 9.23  (354.21)
Day 10 Number Analyzed 5 participants 7 participants
-73.23  (29.34) 212.22  (710.39)
Day 14 Number Analyzed 21 participants 19 participants
-56.62  (97.54) -56.61  (59.19)
Day 28 Number Analyzed 19 participants 14 participants
-66.89  (73.45) -39.63  (161.97)
5.Secondary Outcome
Title Percent Change From Baseline in Ferritin
Hide 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.

Time Frame Days 3, 5, 7, 10, 14, 28
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 25 participants 19 participants
-15.25  (21.87) -7.38  (31.17)
Day 5 Number Analyzed 14 participants 12 participants
-29.67  (25.79) -17.93  (36.74)
Day 7 Number Analyzed 10 participants 8 participants
-36.59  (22.78) -9.67  (45.84)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 29 participants 25 participants
-24.48  (31.30) -20.38  (28.00)
Day 10 Number Analyzed 4 participants 7 participants
-47.58  (31.60) -1.24  (34.52)
Day 14 Number Analyzed 19 participants 18 participants
-45.25  (23.09) -40.20  (26.81)
Day 28 Number Analyzed 18 participants 15 participants
-62.28  (37.27) -63.69  (16.43)
6.Secondary Outcome
Title Percent Change From Baseline in Absolute Lymphocyte Count
Hide 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.

Time Frame Days 3, 5, 7, 10, 14, 28
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 17 participants 17 participants
54.75  (92.83) 34.66  (61.47)
Day 5 Number Analyzed 9 participants 12 participants
28.18  (64.35) 76.86  (63.02)
Day 7 Number Analyzed 6 participants 9 participants
46.22  (72.11) 102.80  (107.71)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 19 participants 20 participants
100.79  (142.10) 97.45  (92.75)
Day 10 Number Analyzed 3 participants 6 participants
67.41  (73.04) 118.26  (66.81)
Day 14 Number Analyzed 14 participants 13 participants
108.55  (110.73) 106.85  (103.52)
Day 28 Number Analyzed 11 participants 11 participants
135.30  (88.00) 127.09  (136.57)
7.Secondary Outcome
Title Overall Survival
Hide 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.
Time Frame From randomization until 90 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Median (90% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The median and lower and upper limit of the 95% confidence interval (CI) could not be calculated as there were an insufficient number of participants with events.
8.Secondary Outcome
Title Percentage of Participants Alive and Discharged From ICU
Hide Description [Not Specified]
Time Frame At Day 14 and at Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Unit of Measure: Percentage of participants
At Day 14 83.9 87.1
At Day 28 83.9 87.1
9.Secondary Outcome
Title Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause
Hide 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.
Time Frame From randomization to 28 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Median (90% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The median and lower and upper limit of the 95% confidence interval (CI) could not be calculated as there were an insufficient number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acalabrutinib + BSC, BSC Alone
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypothesis testing for this endpoint.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments P-value not generated.
Method Regression, Cox
Comments Adjusting for age (<65 vs >=65 years) and comorbidities (present vs absent). Ties handled by Efron approach. HR CI using profile likelihood approach.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.553
Confidence Interval (2-Sided) 90%
0.145 to 1.952
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Days Alive and Free of Respiratory Failure
Hide 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) Noninvasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Time Frame From randomization to 28 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Days
26.2  (6.7) 24.6  (7.3)
11.Secondary Outcome
Title Number of Days With Respiratory Failure
Hide 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) Noninvasive 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.
Time Frame From randomization to 28 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Days
1.8  (6.7) 3.4  (7.3)
12.Secondary Outcome
Title Number of Days Hospitalized
Hide 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.

Time Frame From randomization to 28 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Days
7.6  (7.3) 9.0  (8.5)
13.Secondary Outcome
Title Number of Days in ICU
Hide 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.

Time Frame From randomization to 90 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Days
4.4  (17.1) 7.0  (20.8)
14.Secondary Outcome
Title Number of Days Alive Outside of Hospital
Hide Description [Not Specified]
Time Frame From randomization to 28 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Days
20.2  (7.3) 18.9  (8.6)
15.Secondary Outcome
Title Number of Days Alive Outside of Hospital
Hide Description [Not Specified]
Time Frame From randomization to 90 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (as randomized).
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Days
75.3  (25.2) 72.7  (25.0)
16.Secondary Outcome
Title Percent Change From Baseline in Oxygenation Index
Hide 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.

Time Frame Days 3, 5, 7, 10, 14, 28
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 28 participants 26 participants
14.24  (43.64) 13.51  (30.67)
Day 5 Number Analyzed 16 participants 18 participants
40.25  (74.37) 18.71  (32.17)
Day 7 Number Analyzed 12 participants 12 participants
18.41  (26.19) 28.73  (31.15)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 30 participants 30 participants
32.37  (66.33) 36.67  (39.33)
Day 10 Number Analyzed 4 participants 9 participants
-23.81  (27.53) 33.09  (50.42)
Day 14 Number Analyzed 19 participants 18 participants
54.87  (84.54) 59.22  (43.22)
Day 28 Number Analyzed 18 participants 18 participants
48.87  (51.77) 65.59  (50.76)
17.Secondary Outcome
Title Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale
Hide 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.

Time Frame From randomization to 28 days after randomization.
Hide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (as randomized).

Participants require a baseline and at least one post-baseline result to be included in the number analyzed.

Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 31 29
Median (90% Confidence Interval)
Unit of Measure: Days
6.00
(5.00 to 7.00)
7.00
(5.00 to 11.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Acalabrutinib + BSC, BSC Alone
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypothesis testing for this endpoint.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments P-value not generated.
Method Regression, Cox
Comments Adjusting for age (<65 vs >=65 years) and comorbidities (present vs absent). Ties handled by Efron approach. HR CI using profile likelihood approach.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.314
Confidence Interval (2-Sided) 90%
0.794 to 2.183
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Pharmacokinetics of Acalabrutinib
Hide Description Summary of plasma concentrations (ng/mL) of acalabrutinib
Time Frame Day 3 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: all participants who received at least 1 dose of acalabrutinib and had at least 1 post-dose evaluable pharmacokinetic (PK) data point for acalabrutinib or ACP-5862.
Arm/Group Title Acalabrutinib + BSC
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 3, Pre-dose Number Analyzed 8 participants
6.258
(248%)
Day 3, 0.5 hours post-dose Number Analyzed 14 participants
26.683
(173%)
Day 3, 1 hour post-dose Number Analyzed 10 participants
210.858
(71.5%)
Day 3, 2 hours post-dose Number Analyzed 18 participants
124.143
(89.2%)
Day 3, 4 hours post-dose Number Analyzed 10 participants
33.714
(93.4%)
Day 7, 1 hour post-dose Number Analyzed 1 participants
165.080 [1] 
(NA%)
Day 7, 2 hours post-dose Number Analyzed 0 participants
Day 7, 4 hours post-dose Number Analyzed 1 participants
14.320 [1] 
(NA%)
[1]
Only 1 participant had a result for this timepoint.
19.Secondary Outcome
Title Pharmacokinetics of ACP-5862
Hide Description Summary of plasma concentrations (ng/mL) of ACP-5862
Time Frame Day 3 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: all participants who received at least 1 dose of acalabrutinib and had at least 1 post-dose evaluable pharmacokinetic (PK) data point for acalabrutinib or ACP-5862.
Arm/Group Title Acalabrutinib + BSC
Hide Arm/Group Description:
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
Overall Number of Participants Analyzed 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 3, Pre-dose Number Analyzed 9 participants
53.818
(140%)
Day 3, 0.5 hours post-dose Number Analyzed 14 participants
58.959
(129%)
Day 3, 1 hour post-dose Number Analyzed 10 participants
293.606
(68.1%)
Day 3, 2 hours post-dose Number Analyzed 18 participants
273.528
(50.2%)
Day 3, 4 hours post-dose Number Analyzed 10 participants
178.575
(44.2%)
Day 7, 1 hour post-dose Number Analyzed 1 participants
582.180 [1] 
(NA%)
Day 7, 2 hours post-dose Number Analyzed 0 participants
Day 7, 4 hours post-dose Number Analyzed 1 participants
139.560 [1] 
(NA%)
[1]
Only 1 participant had a result for this timepoint.
Time Frame Screening to 28 (+3) days after last dose of acalabrutinib (for acalabrutinib + BSC treated participants) or to 38 (+3) days after randomization (for BSC alone treated participants)
Adverse Event Reporting Description Population summarized is the safety analysis set (treatment actually received): All participants who received at least 1 dose of acalabrutinib were included in Acalabrutinib + BSC arm, and patients who did not receive any acalabrutinib were included in BSC alone arm.
 
Arm/Group Title Acalabrutinib + BSC BSC Alone
Hide Arm/Group Description Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines. Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
All-Cause Mortality
Acalabrutinib + BSC BSC Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   2/30 (6.67%)      2/32 (6.25%)    
Hide Serious Adverse Events
Acalabrutinib + BSC BSC Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/30 (13.33%)      6/32 (18.75%)    
Gastrointestinal disorders     
Rectal haemorrhage  1  1/30 (3.33%)  1 0/32 (0.00%)  0
Retroperitoneal haematoma  1  1/30 (3.33%)  1 0/32 (0.00%)  0
Hepatobiliary disorders     
Hepatotoxicity  1  1/30 (3.33%)  1 0/32 (0.00%)  0
Portal vein thrombosis  1  0/30 (0.00%)  0 1/32 (3.13%)  1
Infections and infestations     
Pneumonia cytomegaloviral  1  1/30 (3.33%)  1 0/32 (0.00%)  0
Staphylococcal sepsis  1  0/30 (0.00%)  0 1/32 (3.13%)  1
Urinary tract infection  1  0/30 (0.00%)  0 2/32 (6.25%)  2
Investigations     
Haemoglobin decreased  1  0/30 (0.00%)  0 1/32 (3.13%)  1
Renal and urinary disorders     
Chronic kidney disease  1  1/30 (3.33%)  1 0/32 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/30 (0.00%)  0 1/32 (3.13%)  1
Pulmonary embolism  1  0/30 (0.00%)  0 1/32 (3.13%)  1
Respiratory failure  1  0/30 (0.00%)  0 1/32 (3.13%)  1
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Acalabrutinib + BSC BSC Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/30 (16.67%)      3/32 (9.38%)    
Nervous system disorders     
Headache  1  4/30 (13.33%)  4 0/32 (0.00%)  0
Psychiatric disorders     
Insomnia  1  1/30 (3.33%)  1 3/32 (9.38%)  3
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Improvements in BSC (use of corticosteroids and antivirals) have led to a substantial reduction in mortality and morbidity in patients hospitalized with COVID-19, which, in turn, minimizes the impact that additional treatment regimens can have on patient prognosis and recovery. In addition, variability in patient population and the performance of BSC across the globe poses challenges to demonstrate benefit.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

PI shall provide copies of any materials relating to the Study, or the Developed Technologies that either intends to publish or make any presentations relating to, at least 30 days in advance of publication, submission or presentation.

PI shall not include in or shall remove from any proposed publication of any Confidential Information, errors or inaccuracies; and shall withhold publication, submission for publication or presentation for 90 days from the date the Company receives the material.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Information Center
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04380688    
Other Study ID Numbers: D822FC00003
First Submitted: May 7, 2020
First Posted: May 8, 2020
Results First Submitted: August 19, 2021
Results First Posted: September 13, 2021
Last Update Posted: September 13, 2021