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

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ClinicalTrials.gov Identifier: NCT04346199
Recruitment Status : Completed
First Posted : April 15, 2020
Results First Posted : September 13, 2021
Last Update Posted : September 17, 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 177
Recruitment Details All participants had COVID-19 pneumonia (documented radiographically) requiring hospitalization and were recruited from the following countries: South Africa; India; Turkey; Japan; Russian Federation; France; Italy; Brazil; Argentina; Peru; Mexico; Chile. The first participant was randomized on 15 June 2020 and the last participant was randomized on 17 August 2020.
Pre-assignment Details Screening assessments were performed within the 3 days prior to randomization. Of 236 screened participants, 177 were enrolled. Of the 59 participants that were screened but not enrolled, 54 were screen failures (did not meet eligibility criteria), 1 died, 1 was withdrawn by physician decision and 3 withdrew consent.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 89 88
Completed 74 77
Not Completed 15 11
Reason Not Completed
Death             8             9
Lost to Follow-up             0             1
Study terminated by sponsor incorrectly entered in database - participants completed the study             2             0
Withdrawal by Subject             5             1
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 89 88 177
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 89 participants 88 participants 177 participants
56.7  (13.3) 56.7  (14.8) 56.7  (14.1)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 89 participants 88 participants 177 participants
< 65 years 61 60 121
>= 65 years 28 28 56
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 88 participants 177 participants
Female
29
  32.6%
24
  27.3%
53
  29.9%
Male
60
  67.4%
64
  72.7%
124
  70.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 89 participants 88 participants 177 participants
HISPANIC OR LATINO 48 47 95
NOT HISPANIC OR LATINO 41 41 82
NOT REPORTED 0 0 0
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 89 participants 88 participants 177 participants
WHITE 40 48 88
BLACK OR AFRICAN AMERICAN 3 5 8
AMERICAN INDIAN OR ALASKA NATIVE 7 3 10
ASIAN 23 13 36
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 0 0 0
OTHER 14 19 33
NOT REPORTED 2 0 2
1.Primary 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 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
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 89 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
83.1
(74.8 to 91.5)
90.9
(84.3 to 97.5)
2.Secondary 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 (91) is greater than the number of participants randomized to this group (88) because three participants randomized to Acalabrutinib + BSC did not receive any acalabrutinib and therefore are 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 86 91
Measure Type: Count of Participants
Unit of Measure: Participants
Any Adverse Event
43
  50.0%
37
  40.7%
Any Serious Adverse Event
7
   8.1%
2
   2.2%
3.Secondary 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) Non-invasive 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 89 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
84.3
(76.1 to 92.4)
88.6
(81.4 to 95.8)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 64 participants 62 participants
-15.06  (95.82) -15.25  (91.61)
Day 5 Number Analyzed 59 participants 64 participants
-12.48  (113.38) -41.07  (92.59)
Day 7 Number Analyzed 49 participants 49 participants
-45.71  (106.84) -23.41  (223.06)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 79 participants 81 participants
-16.84  (194.71) -29.32  (166.35)
Day 10 Number Analyzed 36 participants 41 participants
-35.53  (126.84) -23.41  (203.02)
Day 14 Number Analyzed 50 participants 64 participants
-12.49  (187.37) -17.26  (256.87)
Day 28 Number Analyzed 42 participants 52 participants
-30.28  (192.90) -63.74  (75.28)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 58 participants 46 participants
9.84  (92.66) 6.49  (40.23)
Day 5 Number Analyzed 51 participants 46 participants
12.92  (105.09) -12.76  (43.18)
Day 7 Number Analyzed 43 participants 38 participants
-8.93  (53.52) -8.79  (36.40)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 70 participants 74 participants
-9.09  (58.85) 1.35  (125.95)
Day 10 Number Analyzed 36 participants 35 participants
-5.99  (73.71) 6.84  (178.23)
Day 14 Number Analyzed 46 participants 55 participants
-18.81  (67.85) -26.80  (46.10)
Day 28 Number Analyzed 39 participants 46 participants
-66.82  (18.24) -66.05  (21.67)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 65 participants 60 participants
31.74  (59.32) 36.82  (79.91)
Day 5 Number Analyzed 59 participants 60 participants
55.79  (101.57) 87.25  (140.37)
Day 7 Number Analyzed 51 participants 48 participants
51.72  (91.82) 79.33  (119.73)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 80 participants 81 participants
78.34  (95.88) 99.65  (149.02)
Day 10 Number Analyzed 41 participants 40 participants
98.55  (113.66) 83.08  (105.56)
Day 14 Number Analyzed 59 participants 65 participants
74.65  (124.47) 91.58  (123.63)
Day 28 Number Analyzed 47 participants 50 participants
89.35  (100.24) 96.62  (97.30)
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. Safety Issue:
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 89 88
Median (95% 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 89 88
Measure Type: Number
Unit of Measure: Percentage of participants
At Day 14 78.7 89.8
At Day 28 83.1 87.5
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 89 88
Median (95% 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 0.758
Confidence Interval (2-Sided) 95%
0.323 to 1.722
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) Non-invasive 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 89 88
Mean (Standard Deviation)
Unit of Measure: Days
24.8  (8.0) 25.3  (7.1)
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 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.
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 89 88
Mean (Standard Deviation)
Unit of Measure: Days
3.2  (8.0) 2.7  (7.1)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Days
12.2  (8.6) 10.4  (7.4)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Days
10.4  (25.5) 9.7  (25.8)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Days
15.1  (8.4) 17.0  (7.3)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Days
66.8  (28.2) 71.3  (24.5)
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 89 88
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 3 Number Analyzed 80 participants 81 participants
11.65  (29.40) 12.20  (33.88)
Day 5 Number Analyzed 73 participants 76 participants
23.94  (41.72) 33.09  (51.50)
Day 7 Number Analyzed 61 participants 61 participants
30.58  (57.79) 54.51  (84.75)
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10) Number Analyzed 86 participants 88 participants
54.25  (71.71) 62.10  (80.79)
Day 10 Number Analyzed 53 participants 48 participants
64.44  (84.02) 80.52  (101.48)
Day 14 Number Analyzed 75 participants 76 participants
70.39  (77.27) 83.71  (84.96)
Day 28 Number Analyzed 54 participants 57 participants
80.93  (89.61) 90.68  (95.43)
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 77 83
Median (95% Confidence Interval)
Unit of Measure: Days
10.00
(8.00 to 12.00)
10.00
(8.00 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 [Not Specified]
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 0.967
Confidence Interval 95%
0.690 to 1.353
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 66
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 3, Pre-dose Number Analyzed 33 participants
15.359
(195.1%)
Day 3, 0.5 hours post-dose Number Analyzed 61 participants
54.580
(139.7%)
Day 3, 1 hour post-dose Number Analyzed 20 participants
56.120
(141.6%)
Day 3, 2 hours post-dose Number Analyzed 61 participants
90.173
(104.3%)
Day 3, 4 hours post-dose Number Analyzed 24 participants
36.841
(179.2%)
Day 3, 6 hours post-dose Number Analyzed 13 participants
23.551
(205.0%)
Day 7, 1 hour post-dose Number Analyzed 7 participants
117.015
(60.3%)
Day 7, 2 hours post-dose Number Analyzed 0 participants
Day 7, 4 hours post-dose Number Analyzed 7 participants
17.454
(108.6%)
Day 7, 6 hours post-dose Number Analyzed 0 participants
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 66
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 3, Pre-dose Number Analyzed 36 participants
71.526
(94.8%)
Day 3, 0.5 hours post-dose Number Analyzed 62 participants
125.332
(109.9%)
Day 3, 1 hour post-dose Number Analyzed 20 participants
144.784
(95.1%)
Day 3, 2 hours post-dose Number Analyzed 63 participants
213.370
(72.7%)
Day 3, 4 hours post-dose Number Analyzed 24 participants
154.437
(70.3%)
Day 3, 6 hours post-dose Number Analyzed 13 participants
113.769
(82.8%)
Day 7, 1 hour post-dose Number Analyzed 8 participants
156.133
(68.0%)
Day 7, 2 hours post-dose Number Analyzed 0 participants
Day 7, 4 hours post-dose Number Analyzed 7 participants
95.392
(69.7%)
Day 7, 6 hours post-dose Number Analyzed 0 participants
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   7/86 (8.14%)      10/91 (10.99%)    
Hide Serious Adverse Events
Acalabrutinib + BSC BSC Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/86 (8.14%)      2/91 (2.20%)    
Infections and infestations     
Bacterial sepsis  1  1/86 (1.16%)  1 0/91 (0.00%)  0
Mucosal infection  1  1/86 (1.16%)  1 0/91 (0.00%)  0
Pneumonia  1  2/86 (2.33%)  2 0/91 (0.00%)  0
Septic shock  1  0/86 (0.00%)  0 1/91 (1.10%)  1
Nervous system disorders     
Ischaemic stroke  1  0/86 (0.00%)  0 1/91 (1.10%)  1
Renal and urinary disorders     
Acute kidney injury  1  1/86 (1.16%)  1 0/91 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/86 (0.00%)  0 1/91 (1.10%)  1
Pleural effusion  1  1/86 (1.16%)  1 0/91 (0.00%)  0
Respiratory failure  1  2/86 (2.33%)  2 0/91 (0.00%)  0
Vascular disorders     
Hypotension  1  1/86 (1.16%)  1 0/91 (0.00%)  0
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   10/86 (11.63%)      2/91 (2.20%)    
Nervous system disorders     
Headache  1  10/86 (11.63%)  11 2/91 (2.20%)  2
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.
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: NCT04346199    
Other Study ID Numbers: D822FC00001
First Submitted: April 9, 2020
First Posted: April 15, 2020
Results First Submitted: September 8, 2021
Results First Posted: September 13, 2021
Last Update Posted: September 17, 2021