Trial Outcomes & Findings for Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury (NCT NCT04375397)
NCT ID: NCT04375397
Last Updated: 2022-06-01
Results Overview
Respiratory failure is defined as a clinical diagnosis of respiratory failure and initiation of one of the following therapies: endotracheal intubation and mechanical ventilation; OR extracorporeal membrane oxygenation; OR high-flow nasal cannula oxygen delivery (i.e., reinforced nasal cannula delivering heated, humidified oxygen with fraction of delivered oxygen ≥ 0.5 and flow rates of ≥ 30 L/min); OR non-invasive positive pressure ventilation; OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation.
COMPLETED
PHASE2
46 participants
Through Day 28
2022-06-01
Participant Flow
Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Participant milestones
| Measure |
Ibrutinib 420 mg + SOC
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
24
|
|
Overall Study
COMPLETED
|
13
|
18
|
|
Overall Study
NOT COMPLETED
|
9
|
6
|
Reasons for withdrawal
| Measure |
Ibrutinib 420 mg + SOC
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Withdrew consent
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
6
|
4
|
|
Overall Study
Other, not specified
|
0
|
1
|
Baseline Characteristics
Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury
Baseline characteristics by cohort
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.1 years
STANDARD_DEVIATION 10.52 • n=5 Participants
|
55.2 years
STANDARD_DEVIATION 11.73 • n=7 Participants
|
52.8 years
STANDARD_DEVIATION 11.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Missing
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
COVID-19 symptom onset duration prior to baseline (days)
|
9.27 days
STANDARD_DEVIATION 2.567 • n=5 Participants
|
9.08 days
STANDARD_DEVIATION 2.765 • n=7 Participants
|
9.17 days
STANDARD_DEVIATION 2.644 • n=5 Participants
|
|
Number of participants with a score of 4 on the WHO-8 ordinal scale at screening
|
22 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Stratification factor of prescription for remdesivir
Yes
|
13 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Stratification factor of prescription for remdesivir
No
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Through Day 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Respiratory failure is defined as a clinical diagnosis of respiratory failure and initiation of one of the following therapies: endotracheal intubation and mechanical ventilation; OR extracorporeal membrane oxygenation; OR high-flow nasal cannula oxygen delivery (i.e., reinforced nasal cannula delivering heated, humidified oxygen with fraction of delivered oxygen ≥ 0.5 and flow rates of ≥ 30 L/min); OR non-invasive positive pressure ventilation; OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Percentage of Participants Alive and Without Respiratory Failure Through Day 28
|
86.4 percentage of participants
Interval 74.4 to 93.2
|
79.2 percentage of participants
Interval 66.9 to 87.7
|
SECONDARY outcome
Timeframe: At Day 14Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug; participants with baseline and Day 14 score data
The WHO-8 is an ordinal scale for clinical improvement with scores ranging from 0 to 8, where a lower score indicates better clinical status. A score of 0 represents uninfected; 1 (ambulatory, no limitation of activities); 2 (ambulatory, limitation of activities); 3 (hospitalized with mild disease, no oxygen therapy); 4 (hospitalized with mild disease, oxygen by mask or nasal prongs); 5 (hospitalized with severe disease, non-invasive ventilation or high-flow oxygen); 6 (hospitalized with severe disease, intubation and mechanical ventilation); 7 (hospitalized with severe disease, ventilation and additional organ support \[pressors, renal replacement therapy, extracorporeal membrane oxygenation\]); and 8 (death). Negative values indicate improvement from baseline.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
-4 points
|
2 Participants
|
3 Participants
|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
-3 points
|
12 Participants
|
9 Participants
|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
-2 points
|
5 Participants
|
7 Participants
|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
-1 point
|
0 Participants
|
2 Participants
|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
0 points
|
1 Participants
|
1 Participants
|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
1 point
|
1 Participants
|
1 Participants
|
|
Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14
3 points
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Days spent on supplemental oxygen was set as the date of the participant being off of supplemental oxygen minus the date of initiation of supplemental oxygen + 1 day. If a participant received more than 1 period of supplemental oxygen therapy during the study or switched from supplemental oxygen to a more intensive therapy, then the days spent on supplemental oxygen were to be calculated as the sum of all the periods where the participant was on supplemental oxygen or a more intensive therapy through Day 28. If the date of the first initiation of supplemental oxygen was before Baseline Day 1, then the days spent on supplemental oxygen were to be calculated from Baseline Day 1 to the date of the participant being off the supplemental oxygen. Time on supplemental oxygen was to be imputed to the maximum number of days on study drug (28) for all points following the death of a participant.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Median Reduction in Days Spent on Supplemental Oxygen
|
5.0 days
Interval 1.0 to 28.0
|
6.5 days
Interval 1.0 to 21.0
|
SECONDARY outcome
Timeframe: At Study Days 7, 14, 21, and 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
The percentage of participants with mortality from any cause was recorded.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
All-Cause Mortality at Study Days 7, 14, 21, and 28
Day 7
|
0 percentage of participants
Interval 0.0 to 6.9
|
0 percentage of participants
Interval 0.0 to 6.4
|
|
All-Cause Mortality at Study Days 7, 14, 21, and 28
Day 14
|
0 percentage of participants
Interval 0.0 to 6.9
|
0 percentage of participants
Interval 0.0 to 6.4
|
|
All-Cause Mortality at Study Days 7, 14, 21, and 28
Day 21
|
4.5 percentage of participants
Interval 1.4 to 14.0
|
0 percentage of participants
Interval 0.0 to 6.4
|
|
All-Cause Mortality at Study Days 7, 14, 21, and 28
Day 28
|
4.5 percentage of participants
Interval 1.4 to 14.0
|
0 percentage of participants
Interval 0.0 to 6.4
|
SECONDARY outcome
Timeframe: At Study Days 7, 14, 21, and 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Respiratory failure is defined as a clinical diagnosis of respiratory failure and initiation of one of the following therapies: endotracheal intubation and mechanical ventilation; OR extracorporeal membrane oxygenation; OR high-flow nasal cannula oxygen delivery (i.e., reinforced nasal cannula delivering heated, humidified oxygen with fraction of delivered oxygen ≥ 0.5 and flow rates of ≥ 30 L/min), OR non-invasive positive pressure ventilation; OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28
Day 7
|
9.1 percentage of participants
Interval 3.8 to 20.0
|
20.8 percentage of participants
Interval 12.3 to 33.1
|
|
Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28
Day 14
|
9.1 percentage of participants
Interval 3.8 to 20.0
|
20.8 percentage of participants
Interval 12.3 to 33.1
|
|
Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28
Day 21
|
13.6 percentage of participants
Interval 6.8 to 25.6
|
20.8 percentage of participants
Interval 12.3 to 33.1
|
|
Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28
Day 28
|
13.6 percentage of participants
Interval 6.8 to 25.6
|
20.8 percentage of participants
Interval 12.3 to 33.1
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Mechanical ventilation-free survival is defined as the number of days from Baseline Day 1 to the date when a participant initiated mechanical ventilation or died, whichever occurred first, during the 28 days post baseline. If the specified event did not occur by Day 28, participants were to be censored. Specifically, a participant without any post-baseline assessment record was to be censored at Baseline Day 1, a participant who prematurely discontinued from study without a record of death or start of mechanical ventilation was to be censored at the earlier timepoint of the date of study discontinuation or Day 28, an ongoing participant in the study without a record of death or start of mechanical ventilation was to be censored at the earlier timepoint of the date of the last evidence that the participant is not on mechanical ventilation or Day 28.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Mechanical Ventilation-Free Survival
|
NA days
Not calculable/estimable due to low number of participants with events
|
NA days
Not calculable/estimable due to low number of participants with events
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Days spent on mechanical ventilation was defined as the date of the participant being off mechanical ventilation - date of initiation of mechanical ventilation + 1 day. If a participant received more than 1 period of mechanical ventilation during the study or switched from mechanical ventilation to a more intensive therapy, then the days spent on mechanical ventilation were to be calculated as the sum of all the periods where the participant is on mechanical ventilation or a more intensive therapy through Day 28.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Days on Mechanical Ventilation
|
0.0 days
Interval 0.0 to 28.0
|
0.0 days
Interval 0.0 to 28.0
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Median duration of hospitalization is defined as the hospitalization discharge date - hospitalization admission date + 1 day. If a participant was hospitalized more than once during the study then the hospitalization time was to be calculated as the sum of all the periods when the participant was hospitalized through Day 28.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Median Duration of Hospitalization
|
6.0 days
Interval 2.0 to 28.0
|
6.5 days
Interval 3.0 to 28.0
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
Time to discharge from hospital is defined as the number of days from Baseline Day 1 to the date of the last evidence that a participant is last discharged from hospital, during the 28 days post baseline. If the specified event did not occur by Day 28, participants were censored. Specifically, a participant without any postbaseline assessment record was to be censored at Baseline Day 1, a participant who died was to have time to discharge from hospital censored at Day 28, a participant who prematurely discontinued from study without a record of hospitalization discharge was to be censored at the earlier timepoint of the date of study discontinuation or Day 28, an on-going participant in the study without a record of hospitalization discharge was to be censored at the earlier timepoint of the date of the last evidence that the participant is hospitalized or Day 28.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Time to Discharge From Hospital
|
6.0 days
Interval 5.0 to 10.0
|
6.5 days
Interval 5.0 to 9.0
|
SECONDARY outcome
Timeframe: At Study Days 7, 14, 21, and 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug. Participants with non-missing baseline and at least one post-baseline value are included in the analyses.
The PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2). A PaO2/FiO2 ratio of 300 to 200 is mild, 200 to 100 moderate, and \<100 is severe Adult Respiratory Distress Syndrome (ARDS).
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=2 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=3 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio
Day 7
|
100 mmHg
Standard Deviation 56.07
|
87 mmHg
Standard Deviation 33.35
|
|
Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio
Day 21
|
269 mmHg
|
—
|
SECONDARY outcome
Timeframe: At Study Days 7, 14, 21, and 28Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug. Participants with non-missing baseline and at least one post-baseline value are included in the analyses.
The oxygenation index is used to assess the intensity of ventilatory support required to maintain oxygenation. An index of 0 to \< 25 is predictive of a good outcome; 25 to \<40 indicates a chance of death \>40%; and an index of 40 to 1000 warrants consideration of extracorporeal membrane oxygenation (ECMO).
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=2 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=2 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Oxygenation Index
Day 7
|
14 units on a scale
|
—
|
|
Oxygenation Index
Day 14
|
19 units on a scale
|
12 units on a scale
|
|
Oxygenation Index
Day 21
|
33 units on a scale
Standard Deviation 43.61
|
20 units on a scale
Standard Deviation 1.75
|
|
Oxygenation Index
Day 28
|
—
|
12 units on a scale
Standard Deviation 4.26
|
SECONDARY outcome
Timeframe: From first dose of study drug until 30 days following last dose of study drug (up to 70 days)Population: Safety Population: all participants who received at least 1 dose of study drug
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Outcome measures
| Measure |
Ibrutinib 420 mg + SOC
n=22 Participants
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 Participants
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Number of Participants With Adverse Events
|
12 Participants
|
12 Participants
|
Adverse Events
Ibrutinib 420 mg + SOC
Placebo + SOC
Serious adverse events
| Measure |
Ibrutinib 420 mg + SOC
n=22 participants at risk
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 participants at risk
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/22 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
4.2%
1/24 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Infections and infestations
PNEUMONIA BACTERIAL
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
0.00%
0/24 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Infections and infestations
SEPSIS
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
4.2%
1/24 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Infections and infestations
SEPTIC SHOCK
|
0.00%
0/22 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
8.3%
2/24 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Infections and infestations
STAPHYLOCOCCAL BACTERAEMIA
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
0.00%
0/24 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
0.00%
0/22 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
8.3%
2/24 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
12.5%
3/24 • Number of events 3 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HAEMORRHAGE
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
0.00%
0/24 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Vascular disorders
PERIPHERAL ARTERY THROMBOSIS
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
0.00%
0/24 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
Other adverse events
| Measure |
Ibrutinib 420 mg + SOC
n=22 participants at risk
420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
Placebo + SOC
n=24 participants at risk
Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
13.6%
3/22 • Number of events 3 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
8.3%
2/24 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Gastrointestinal disorders
NAUSEA
|
9.1%
2/22 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
4.2%
1/24 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
9.1%
2/22 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
12.5%
3/24 • Number of events 3 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
4.5%
1/22 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
8.3%
2/24 • Number of events 2 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
|
Vascular disorders
HYPERTENSION
|
13.6%
3/22 • Number of events 3 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
4.2%
1/24 • Number of events 1 • All-cause mortality is reported from enrollment to the end of study; median time on follow-up was Ibrutinib 420 mg + SOC (58.0 days); and Placebo + SOC (62.0 days). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 70 days.
All-cause mortality and adverse events: all participants who received at least one dose of study drug
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER