Trial Outcomes & Findings for Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19. (NCT NCT04346199)
NCT ID: NCT04346199
Last Updated: 2021-09-17
Results Overview
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
COMPLETED
PHASE2
177 participants
At Day 14
2021-09-17
Participant Flow
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.
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that were screened but not enrolled, 54 were screen failures (did not meet eligibility criteria), 1 died, 1 was withdrawn by physician decision and 3 withdrew consent.
Participant milestones
| Measure |
Acalabrutinib + BSC
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Overall Study
STARTED
|
89
|
88
|
|
Overall Study
COMPLETED
|
74
|
77
|
|
Overall Study
NOT COMPLETED
|
15
|
11
|
Reasons for withdrawal
| Measure |
Acalabrutinib + BSC
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Overall Study
Death
|
8
|
9
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Study terminated by sponsor incorrectly entered in database - participants completed the study
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
Baseline Characteristics
Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.
Baseline characteristics by cohort
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
Total
n=177 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.7 Years
STANDARD_DEVIATION 13.3 • n=99 Participants
|
56.7 Years
STANDARD_DEVIATION 14.8 • n=107 Participants
|
56.7 Years
STANDARD_DEVIATION 14.1 • n=206 Participants
|
|
Age, Customized
< 65 years
|
61 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
121 Participants
n=206 Participants
|
|
Age, Customized
>= 65 years
|
28 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
56 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=99 Participants
|
64 Participants
n=107 Participants
|
124 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
HISPANIC OR LATINO
|
48 Participants
n=99 Participants
|
47 Participants
n=107 Participants
|
95 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
NOT HISPANIC OR LATINO
|
41 Participants
n=99 Participants
|
41 Participants
n=107 Participants
|
82 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
NOT REPORTED
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
WHITE
|
40 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
88 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
BLACK OR AFRICAN AMERICAN
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
AMERICAN INDIAN OR ALASKA NATIVE
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
ASIAN
|
23 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
OTHER
|
14 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: At Day 14Population: Full analysis set (as randomized).
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 measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percentage of Participants Alive and Free of Respiratory Failure at Day 14
|
83.1 Percentage of participants
Interval 74.8 to 91.5
|
90.9 Percentage of participants
Interval 84.3 to 97.5
|
SECONDARY outcome
Timeframe: 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)Population: 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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=86 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=91 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any Serious Adverse Event
|
7 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any Adverse Event
|
43 Participants
|
37 Participants
|
SECONDARY outcome
Timeframe: At Day 28Population: Full analysis set (as randomized).
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 measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percentage of Participants Alive and Free of Respiratory Failure at Day 28
|
84.3 Percentage of participants
Interval 76.1 to 92.4
|
88.6 Percentage of participants
Interval 81.4 to 95.8
|
SECONDARY outcome
Timeframe: Days 3, 5, 7, 10, 14, 28Population: 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.
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percent Change From Baseline in C-reactive Protein.
Day 3
|
-15.06 Percent change
Standard Deviation 95.82
|
-15.25 Percent change
Standard Deviation 91.61
|
|
Percent Change From Baseline in C-reactive Protein.
Day 5
|
-12.48 Percent change
Standard Deviation 113.38
|
-41.07 Percent change
Standard Deviation 92.59
|
|
Percent Change From Baseline in C-reactive Protein.
Day 7
|
-45.71 Percent change
Standard Deviation 106.84
|
-23.41 Percent change
Standard Deviation 223.06
|
|
Percent Change From Baseline in C-reactive Protein.
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
-16.84 Percent change
Standard Deviation 194.71
|
-29.32 Percent change
Standard Deviation 166.35
|
|
Percent Change From Baseline in C-reactive Protein.
Day 10
|
-35.53 Percent change
Standard Deviation 126.84
|
-23.41 Percent change
Standard Deviation 203.02
|
|
Percent Change From Baseline in C-reactive Protein.
Day 14
|
-12.49 Percent change
Standard Deviation 187.37
|
-17.26 Percent change
Standard Deviation 256.87
|
|
Percent Change From Baseline in C-reactive Protein.
Day 28
|
-30.28 Percent change
Standard Deviation 192.90
|
-63.74 Percent change
Standard Deviation 75.28
|
SECONDARY outcome
Timeframe: Days 3, 5, 7, 10, 14, 28Population: 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.
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percent Change From Baseline in Ferritin
Day 3
|
9.84 Percent change
Standard Deviation 92.66
|
6.49 Percent change
Standard Deviation 40.23
|
|
Percent Change From Baseline in Ferritin
Day 5
|
12.92 Percent change
Standard Deviation 105.09
|
-12.76 Percent change
Standard Deviation 43.18
|
|
Percent Change From Baseline in Ferritin
Day 7
|
-8.93 Percent change
Standard Deviation 53.52
|
-8.79 Percent change
Standard Deviation 36.40
|
|
Percent Change From Baseline in Ferritin
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
-9.09 Percent change
Standard Deviation 58.85
|
1.35 Percent change
Standard Deviation 125.95
|
|
Percent Change From Baseline in Ferritin
Day 10
|
-5.99 Percent change
Standard Deviation 73.71
|
6.84 Percent change
Standard Deviation 178.23
|
|
Percent Change From Baseline in Ferritin
Day 14
|
-18.81 Percent change
Standard Deviation 67.85
|
-26.80 Percent change
Standard Deviation 46.10
|
|
Percent Change From Baseline in Ferritin
Day 28
|
-66.82 Percent change
Standard Deviation 18.24
|
-66.05 Percent change
Standard Deviation 21.67
|
SECONDARY outcome
Timeframe: Days 3, 5, 7, 10, 14, 28Population: 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.
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 3
|
31.74 Percent change
Standard Deviation 59.32
|
36.82 Percent change
Standard Deviation 79.91
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 5
|
55.79 Percent change
Standard Deviation 101.57
|
87.25 Percent change
Standard Deviation 140.37
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 7
|
51.72 Percent change
Standard Deviation 91.82
|
79.33 Percent change
Standard Deviation 119.73
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
78.34 Percent change
Standard Deviation 95.88
|
99.65 Percent change
Standard Deviation 149.02
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 10
|
98.55 Percent change
Standard Deviation 113.66
|
83.08 Percent change
Standard Deviation 105.56
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 14
|
74.65 Percent change
Standard Deviation 124.47
|
91.58 Percent change
Standard Deviation 123.63
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 28
|
89.35 Percent change
Standard Deviation 100.24
|
96.62 Percent change
Standard Deviation 97.30
|
SECONDARY outcome
Timeframe: From randomization until 90 days after randomization. Safety Issue:Population: Full analysis set (as randomized).
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 measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Overall Survival
|
NA Days
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.
|
NA Days
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.
|
SECONDARY outcome
Timeframe: At Day 14 and at Day 28Population: Full analysis set (as randomized).
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percentage of Participants Alive and Discharged From ICU
At Day 14
|
78.7 Percentage of participants
|
89.8 Percentage of participants
|
|
Percentage of Participants Alive and Discharged From ICU
At Day 28
|
83.1 Percentage of participants
|
87.5 Percentage of participants
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized).
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 measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause
|
NA Days
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.
|
NA Days
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.
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized).
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 measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Alive and Free of Respiratory Failure
|
24.8 Days
Standard Deviation 8.0
|
25.3 Days
Standard Deviation 7.1
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized).
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 measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days With Respiratory Failure
|
3.2 Days
Standard Deviation 8.0
|
2.7 Days
Standard Deviation 7.1
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized).
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Hospitalized
|
12.2 Days
Standard Deviation 8.6
|
10.4 Days
Standard Deviation 7.4
|
SECONDARY outcome
Timeframe: From randomization to 90 days after randomization.Population: Full analysis set (as randomized).
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days in ICU
|
10.4 Days
Standard Deviation 25.5
|
9.7 Days
Standard Deviation 25.8
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized).
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Alive Outside of Hospital
|
15.1 Days
Standard Deviation 8.4
|
17.0 Days
Standard Deviation 7.3
|
SECONDARY outcome
Timeframe: From randomization to 90 days after randomization.Population: Full analysis set (as randomized).
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Alive Outside of Hospital
|
66.8 Days
Standard Deviation 28.2
|
71.3 Days
Standard Deviation 24.5
|
SECONDARY outcome
Timeframe: Days 3, 5, 7, 10, 14, 28Population: 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.
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=89 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=88 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percent Change From Baseline in Oxygenation Index
Day 3
|
11.65 Percent change
Standard Deviation 29.40
|
12.20 Percent change
Standard Deviation 33.88
|
|
Percent Change From Baseline in Oxygenation Index
Day 5
|
23.94 Percent change
Standard Deviation 41.72
|
33.09 Percent change
Standard Deviation 51.50
|
|
Percent Change From Baseline in Oxygenation Index
Day 7
|
30.58 Percent change
Standard Deviation 57.79
|
54.51 Percent change
Standard Deviation 84.75
|
|
Percent Change From Baseline in Oxygenation Index
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
54.25 Percent change
Standard Deviation 71.71
|
62.10 Percent change
Standard Deviation 80.79
|
|
Percent Change From Baseline in Oxygenation Index
Day 10
|
64.44 Percent change
Standard Deviation 84.02
|
80.52 Percent change
Standard Deviation 101.48
|
|
Percent Change From Baseline in Oxygenation Index
Day 14
|
70.39 Percent change
Standard Deviation 77.27
|
83.71 Percent change
Standard Deviation 84.96
|
|
Percent Change From Baseline in Oxygenation Index
Day 28
|
80.93 Percent change
Standard Deviation 89.61
|
90.68 Percent change
Standard Deviation 95.43
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized). Participants require a baseline and at least one post-baseline result to be included in the number analyzed.
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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=77 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=83 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale
|
10.00 Days
Interval 8.0 to 12.0
|
10.00 Days
Interval 8.0 to 11.0
|
SECONDARY outcome
Timeframe: Day 3 and Day 7Population: 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.
Summary of plasma concentrations (ng/mL) of acalabrutinib
Outcome measures
| Measure |
Acalabrutinib + BSC
n=66 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Pharmacokinetics of Acalabrutinib
Day 3, Pre-dose
|
15.359 ng/mL
Geometric Coefficient of Variation 195.1
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 0.5 hours post-dose
|
54.580 ng/mL
Geometric Coefficient of Variation 139.7
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 1 hour post-dose
|
56.120 ng/mL
Geometric Coefficient of Variation 141.6
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 2 hours post-dose
|
90.173 ng/mL
Geometric Coefficient of Variation 104.3
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 4 hours post-dose
|
36.841 ng/mL
Geometric Coefficient of Variation 179.2
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 6 hours post-dose
|
23.551 ng/mL
Geometric Coefficient of Variation 205.0
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 7, 1 hour post-dose
|
117.015 ng/mL
Geometric Coefficient of Variation 60.3
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 7, 4 hours post-dose
|
17.454 ng/mL
Geometric Coefficient of Variation 108.6
|
—
|
SECONDARY outcome
Timeframe: Day 3 and Day 7Population: 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.
Summary of plasma concentrations (ng/mL) of ACP-5862
Outcome measures
| Measure |
Acalabrutinib + BSC
n=66 Participants
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Pharmacokinetics of ACP-5862
Day 3, Pre-dose
|
71.526 ng/mL
Geometric Coefficient of Variation 94.8
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 0.5 hours post-dose
|
125.332 ng/mL
Geometric Coefficient of Variation 109.9
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 1 hour post-dose
|
144.784 ng/mL
Geometric Coefficient of Variation 95.1
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 2 hours post-dose
|
213.370 ng/mL
Geometric Coefficient of Variation 72.7
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 4 hours post-dose
|
154.437 ng/mL
Geometric Coefficient of Variation 70.3
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 6 hours post-dose
|
113.769 ng/mL
Geometric Coefficient of Variation 82.8
|
—
|
|
Pharmacokinetics of ACP-5862
Day 7, 1 hour post-dose
|
156.133 ng/mL
Geometric Coefficient of Variation 68.0
|
—
|
|
Pharmacokinetics of ACP-5862
Day 7, 4 hours post-dose
|
95.392 ng/mL
Geometric Coefficient of Variation 69.7
|
—
|
Adverse Events
Acalabrutinib + BSC
BSC Alone
Serious adverse events
| Measure |
Acalabrutinib + BSC
n=86 participants at risk
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=91 participants at risk
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Infections and infestations
Bacterial sepsis
|
1.2%
1/86 • Number of events 1 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
|
Infections and infestations
Mucosal infection
|
1.2%
1/86 • Number of events 1 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
|
Infections and infestations
Pneumonia
|
2.3%
2/86 • Number of events 2 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
|
Infections and infestations
Septic shock
|
0.00%
0/86 • 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)
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.
|
1.1%
1/91 • Number of events 1 • 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)
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.
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/86 • 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)
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.
|
1.1%
1/91 • Number of events 1 • 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)
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.
|
|
Renal and urinary disorders
Acute kidney injury
|
1.2%
1/86 • Number of events 1 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/86 • 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)
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.
|
1.1%
1/91 • Number of events 1 • 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)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.2%
1/86 • Number of events 1 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.3%
2/86 • Number of events 2 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
|
Vascular disorders
Hypotension
|
1.2%
1/86 • Number of events 1 • 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)
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.
|
0.00%
0/91 • 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)
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.
|
Other adverse events
| Measure |
Acalabrutinib + BSC
n=86 participants at risk
Participants received acalabrutinib 100mg tablet orally twice daily for 10 days, plus best supportive care per the discretion of the Investigator and institutional guidelines.
|
BSC Alone
n=91 participants at risk
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Nervous system disorders
Headache
|
11.6%
10/86 • Number of events 11 • 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)
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.
|
2.2%
2/91 • Number of events 2 • 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)
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place