Trial Outcomes & Findings for Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19. (NCT NCT04380688)
NCT ID: NCT04380688
Last Updated: 2021-09-13
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
62 participants
Primary 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)
Results posted on
2021-09-13
Participant Flow
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.
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.
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
|
31
|
31
|
|
Overall Study
COMPLETED
|
24
|
22
|
|
Overall Study
NOT COMPLETED
|
7
|
9
|
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
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
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=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.5 Years
STANDARD_DEVIATION 13.3 • n=99 Participants
|
51.9 Years
STANDARD_DEVIATION 14.3 • n=107 Participants
|
52.2 Years
STANDARD_DEVIATION 13.7 • n=206 Participants
|
|
Age, Customized
< 65 years
|
26 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
51 Participants
n=206 Participants
|
|
Age, Customized
>= 65 years
|
5 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
40 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
HISPANIC OR LATINO
|
15 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
NOT HISPANIC OR LATINO
|
16 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
NOT REPORTED
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
MISSING
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
WHITE
|
18 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
BLACK OR AFRICAN AMERICAN
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
AMERICAN INDIAN OR ALASKA NATIVE
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
ASIAN
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 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
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
PRIMARY 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 (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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=30 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=32 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 Adverse Event
|
17 Participants
|
15 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any Serious Adverse Event
|
4 Participants
|
6 Participants
|
PRIMARY 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) Noninvasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Outcome measures
| Measure |
Acalabrutinib + BSC
n=31 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=31 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
|
80.6 Percentage of participants
Interval 67.4 to 93.9
|
83.9 Percentage of participants
Interval 71.4 to 96.3
|
SECONDARY 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 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
Outcome measures
| Measure |
Acalabrutinib + BSC
n=31 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=31 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
|
80.6 Percentage of participants
Interval 67.4 to 93.9
|
87.1 Percentage of participants
Interval 75.6 to 98.6
|
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=31 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=31 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
|
-41.08 Percent change
Standard Deviation 71.27
|
-26.74 Percent change
Standard Deviation 69.02
|
|
Percent Change From Baseline in C-reactive Protein.
Day 5
|
-72.05 Percent change
Standard Deviation 26.29
|
-49.55 Percent change
Standard Deviation 54.97
|
|
Percent Change From Baseline in C-reactive Protein.
Day 7
|
-75.72 Percent change
Standard Deviation 29.48
|
-40.53 Percent change
Standard Deviation 75.99
|
|
Percent Change From Baseline in C-reactive Protein.
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
-73.85 Percent change
Standard Deviation 27.92
|
9.23 Percent change
Standard Deviation 354.21
|
|
Percent Change From Baseline in C-reactive Protein.
Day 10
|
-73.23 Percent change
Standard Deviation 29.34
|
212.22 Percent change
Standard Deviation 710.39
|
|
Percent Change From Baseline in C-reactive Protein.
Day 14
|
-56.62 Percent change
Standard Deviation 97.54
|
-56.61 Percent change
Standard Deviation 59.19
|
|
Percent Change From Baseline in C-reactive Protein.
Day 28
|
-66.89 Percent change
Standard Deviation 73.45
|
-39.63 Percent change
Standard Deviation 161.97
|
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=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percent Change From Baseline in Ferritin
Day 3
|
-15.25 Percent change
Standard Deviation 21.87
|
-7.38 Percent change
Standard Deviation 31.17
|
|
Percent Change From Baseline in Ferritin
Day 5
|
-29.67 Percent change
Standard Deviation 25.79
|
-17.93 Percent change
Standard Deviation 36.74
|
|
Percent Change From Baseline in Ferritin
Day 7
|
-36.59 Percent change
Standard Deviation 22.78
|
-9.67 Percent change
Standard Deviation 45.84
|
|
Percent Change From Baseline in Ferritin
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
-24.48 Percent change
Standard Deviation 31.30
|
-20.38 Percent change
Standard Deviation 28.00
|
|
Percent Change From Baseline in Ferritin
Day 10
|
-47.58 Percent change
Standard Deviation 31.60
|
-1.24 Percent change
Standard Deviation 34.52
|
|
Percent Change From Baseline in Ferritin
Day 14
|
-45.25 Percent change
Standard Deviation 23.09
|
-40.20 Percent change
Standard Deviation 26.81
|
|
Percent Change From Baseline in Ferritin
Day 28
|
-62.28 Percent change
Standard Deviation 37.27
|
-63.69 Percent change
Standard Deviation 16.43
|
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=31 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=31 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
|
54.75 Percent change
Standard Deviation 92.83
|
34.66 Percent change
Standard Deviation 61.47
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 5
|
28.18 Percent change
Standard Deviation 64.35
|
76.86 Percent change
Standard Deviation 63.02
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 7
|
46.22 Percent change
Standard Deviation 72.11
|
102.80 Percent change
Standard Deviation 107.71
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
100.79 Percent change
Standard Deviation 142.10
|
97.45 Percent change
Standard Deviation 92.75
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 10
|
67.41 Percent change
Standard Deviation 73.04
|
118.26 Percent change
Standard Deviation 66.81
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 14
|
108.55 Percent change
Standard Deviation 110.73
|
106.85 Percent change
Standard Deviation 103.52
|
|
Percent Change From Baseline in Absolute Lymphocyte Count
Day 28
|
135.30 Percent change
Standard Deviation 88.00
|
127.09 Percent change
Standard Deviation 136.57
|
SECONDARY outcome
Timeframe: From randomization until 90 days after randomization.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=31 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=31 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=31 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=31 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
|
83.9 Percentage of participants
|
87.1 Percentage of participants
|
|
Percentage of Participants Alive and Discharged From ICU
At Day 28
|
83.9 Percentage of participants
|
87.1 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=31 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=31 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) Noninvasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation
Outcome measures
| Measure |
Acalabrutinib + BSC
n=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Alive and Free of Respiratory Failure
|
26.2 Days
Standard Deviation 6.7
|
24.6 Days
Standard Deviation 7.3
|
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) 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.
Outcome measures
| Measure |
Acalabrutinib + BSC
n=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days With Respiratory Failure
|
1.8 Days
Standard Deviation 6.7
|
3.4 Days
Standard Deviation 7.3
|
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=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Hospitalized
|
7.6 Days
Standard Deviation 7.3
|
9.0 Days
Standard Deviation 8.5
|
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=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days in ICU
|
4.4 Days
Standard Deviation 17.1
|
7.0 Days
Standard Deviation 20.8
|
SECONDARY outcome
Timeframe: From randomization to 28 days after randomization.Population: Full analysis set (as randomized).
Outcome measures
| Measure |
Acalabrutinib + BSC
n=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Alive Outside of Hospital
|
20.2 Days
Standard Deviation 7.3
|
18.9 Days
Standard Deviation 8.6
|
SECONDARY outcome
Timeframe: From randomization to 90 days after randomization.Population: Full analysis set (as randomized).
Outcome measures
| Measure |
Acalabrutinib + BSC
n=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Number of Days Alive Outside of Hospital
|
75.3 Days
Standard Deviation 25.2
|
72.7 Days
Standard Deviation 25.0
|
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=31 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=31 Participants
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Percent Change From Baseline in Oxygenation Index
Day 3
|
14.24 Percent change
Standard Deviation 43.64
|
13.51 Percent change
Standard Deviation 30.67
|
|
Percent Change From Baseline in Oxygenation Index
Day 5
|
40.25 Percent change
Standard Deviation 74.37
|
18.71 Percent change
Standard Deviation 32.17
|
|
Percent Change From Baseline in Oxygenation Index
Day 7
|
18.41 Percent change
Standard Deviation 26.19
|
28.73 Percent change
Standard Deviation 31.15
|
|
Percent Change From Baseline in Oxygenation Index
Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)
|
32.37 Percent change
Standard Deviation 66.33
|
36.67 Percent change
Standard Deviation 39.33
|
|
Percent Change From Baseline in Oxygenation Index
Day 10
|
-23.81 Percent change
Standard Deviation 27.53
|
33.09 Percent change
Standard Deviation 50.42
|
|
Percent Change From Baseline in Oxygenation Index
Day 14
|
54.87 Percent change
Standard Deviation 84.54
|
59.22 Percent change
Standard Deviation 43.22
|
|
Percent Change From Baseline in Oxygenation Index
Day 28
|
48.87 Percent change
Standard Deviation 51.77
|
65.59 Percent change
Standard Deviation 50.76
|
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=31 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=29 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
|
6.00 Days
Interval 5.0 to 7.0
|
7.00 Days
Interval 5.0 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=30 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
|
6.258 ng/mL
Geometric Coefficient of Variation 248
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 0.5 hours post-dose
|
26.683 ng/mL
Geometric Coefficient of Variation 173
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 1 hour post-dose
|
210.858 ng/mL
Geometric Coefficient of Variation 71.5
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 2 hours post-dose
|
124.143 ng/mL
Geometric Coefficient of Variation 89.2
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 3, 4 hours post-dose
|
33.714 ng/mL
Geometric Coefficient of Variation 93.4
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 7, 1 hour post-dose
|
165.080 ng/mL
Geometric Coefficient of Variation NA
Only 1 participant had a result for this timepoint.
|
—
|
|
Pharmacokinetics of Acalabrutinib
Day 7, 4 hours post-dose
|
14.320 ng/mL
Geometric Coefficient of Variation NA
Only 1 participant had a result for this timepoint.
|
—
|
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=30 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
|
53.818 ng/mL
Geometric Coefficient of Variation 140
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 0.5 hours post-dose
|
58.959 ng/mL
Geometric Coefficient of Variation 129
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 1 hour post-dose
|
293.606 ng/mL
Geometric Coefficient of Variation 68.1
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 2 hours post-dose
|
273.528 ng/mL
Geometric Coefficient of Variation 50.2
|
—
|
|
Pharmacokinetics of ACP-5862
Day 3, 4 hours post-dose
|
178.575 ng/mL
Geometric Coefficient of Variation 44.2
|
—
|
|
Pharmacokinetics of ACP-5862
Day 7, 1 hour post-dose
|
582.180 ng/mL
Geometric Coefficient of Variation NA
Only 1 participant had a result for this timepoint.
|
—
|
|
Pharmacokinetics of ACP-5862
Day 7, 4 hours post-dose
|
139.560 ng/mL
Geometric Coefficient of Variation NA
Only 1 participant had a result for this timepoint.
|
—
|
Adverse Events
Acalabrutinib + BSC
Serious events: 4 serious events
Other events: 5 other events
Deaths: 2 deaths
BSC Alone
Serious events: 6 serious events
Other events: 3 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Acalabrutinib + BSC
n=30 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=32 participants at risk
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Gastrointestinal disorders
Rectal haemorrhage
|
3.3%
1/30 • 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%
0/32 • 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.
|
|
Gastrointestinal disorders
Retroperitoneal haematoma
|
3.3%
1/30 • 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%
0/32 • 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.
|
|
Hepatobiliary disorders
Hepatotoxicity
|
3.3%
1/30 • 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%
0/32 • 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.
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/30 • 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.
|
3.1%
1/32 • 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.
|
|
Infections and infestations
Pneumonia cytomegaloviral
|
3.3%
1/30 • 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%
0/32 • 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
Staphylococcal sepsis
|
0.00%
0/30 • 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.
|
3.1%
1/32 • 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.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/30 • 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.
|
6.2%
2/32 • 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.
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/30 • 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.
|
3.1%
1/32 • 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
Chronic kidney disease
|
3.3%
1/30 • 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%
0/32 • 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%
0/30 • 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.
|
3.1%
1/32 • 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
Pulmonary embolism
|
0.00%
0/30 • 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.
|
3.1%
1/32 • 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
Respiratory failure
|
0.00%
0/30 • 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.
|
3.1%
1/32 • 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.
|
Other adverse events
| Measure |
Acalabrutinib + BSC
n=30 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=32 participants at risk
Participants received best supportive care per the discretion of the Investigator and institutional guidelines.
|
|---|---|---|
|
Nervous system disorders
Headache
|
13.3%
4/30 • Number of events 4 • 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%
0/32 • 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.
|
|
Psychiatric disorders
Insomnia
|
3.3%
1/30 • 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.
|
9.4%
3/32 • Number of events 3 • 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 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.
- Publication restrictions are in place
Restriction type: OTHER