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| Name | Class |
|---|---|
| Janssen Research & Development LLC; Pharmacyclics LLC (An AbbVie Company) | UNKNOWN |
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Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study was to evaluate if ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection.
This was a Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the addition of ibrutinib to supportive care in hospitalized participants who presented with COVID-19- related pulmonary distress requiring supplemental oxygen. Participants were randomized in a 1:1 ratio to receive placebo + supportive care, denoted as SOC or standard-of-care, or ibrutinib 420 mg + SOC, with randomization stratified by prescription for remdesivir.
Participants were to be treated with either placebo or ibrutinib in addition to supportive care for up to 28 days unless they met treatment discontinuation criteria and were to be followed for 58 days following start of therapy or until death, whichever occurred first. Treatment could have been stopped at the discretion of the treating physician after 14 days if the participant was clinically stable and had been off supplemental oxygen for > 48 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ibrutinib 420 mg + SOC | Experimental | 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 | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibrutinib | Drug | Capsules were to be administered orally with water once daily. For participants who required nasogastric tube (NGT) placement while on study, capsules may have been administered by opening the capsules, mixing with water, and flushing down the NGT. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Alive and Without Respiratory Failure Through Day 28 | 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. | Through Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
Respiratory failure at time of screening as defined per protocol with any of these following therapies:
Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
On a Bruton's tyrosine kinase (BTK)-inhibitor, anti-interleukin 6 (IL6), anti-interleukin 6R (IL6R), or Janus kinase inhibitor (JAKi)
Has received rituximab within 180 days from study entry.
Known bleeding disorders
Major surgery within 4 weeks of study entry
Participants in whom surgery is anticipated to be necessary within 72 hours
History of stroke or bleeding around or within brain within 6 months prior to enrollment
Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV)
Currently active, clinically significant cardiovascular disease
Asymptomatic arrythmias and or history of ejection fraction < 40% on an echo
Participants receiving a strong cytochrome P450 (CYP) 3A4 inhibitor with the exception of those receiving anti-fungal therapy/prophylaxis
Chronic liver disease and hepatic impairment meeting Child Pugh class C
Female participants who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 1 month of last dose of study drug. Male participants who plan to father a child while enrolled in this study or within 3 months after the last dose of study drug.
Unwilling or unable to participate in all required study evaluations and procedures
Vaccinated with a live, attenuated vaccine within 4 weeks
Uncontrolled high blood pressure
On therapeutic anticoagulation at baseline
Participants with cancer, history of interstitial lung disease, and/or history of malignancies as defined in the protocol
Co-enrolled in another interventional trial
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3.0 × ULN, and total bilirubin > 2.0 × ULN
International normalized ratio (INR) ≥ 1.5 × ULN attributable to coagulation disorders
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Med /ID# 221954 | Stanford | California | 94305-2200 | United States | ||
| Medstar Washington Hospital Center /ID# 221886 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35493119 | Derived | Coutre SE, Barnett C, Osiyemi O, Hoda D, Ramgopal M, Fort AC, Qaqish R, Hu Y, Ninomoto J, Alami NN, Styles L, Treon SP. Ibrutinib for Hospitalized Adults With Severe Coronavirus Disease 2019 Infection: Results of the Randomized, Double-Blind, Placebo-Controlled iNSPIRE Study. Open Forum Infect Dis. 2022 Mar 24;9(5):ofac104. doi: 10.1093/ofid/ofac104. eCollection 2022 May. |
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AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Requests for access to individual participant data from ibrutinib clinical studies conducted by AbbVie can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu
Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | Placebo + SOC |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 6, 2020 | Apr 22, 2022 |
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| Placebo | Drug | Capsules were to be administered orally with water once daily. For participants who required nasogastric tube (NGT) placement while on study, capsules may have been administered by opening the capsules, mixing with water, and flushing down the NGT. |
|
| At Day 14 |
| Median Reduction in Days Spent on Supplemental Oxygen | 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. | Up to Day 28 |
| All-Cause Mortality at Study Days 7, 14, 21, and 28 | The percentage of participants with mortality from any cause was recorded. | At Study Days 7, 14, 21, and 28 |
| Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28 | 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. | At Study Days 7, 14, 21, and 28 |
| Mechanical Ventilation-Free Survival | 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. | Up to Day 28 |
| Days on Mechanical Ventilation | 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. | Up to Day 28 |
| Median Duration of Hospitalization | 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. | Up to Day 28 |
| Time to Discharge From Hospital | 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. | Up to Day 28 |
| Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio | 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). | At Study Days 7, 14, 21, and 28 |
| Oxygenation Index | 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). | At Study Days 7, 14, 21, and 28 |
| Number of Participants With Adverse Events | 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. | From first dose of study drug until 30 days following last dose of study drug (up to 70 days) |
| Washington D.C. |
| District of Columbia |
| 20010-3017 |
| United States |
| Duplicate_GW Medical Faculty Associates /ID# 222023 | Washington D.C. | District of Columbia | 20037 | United States |
| Midway Immunology and Research /ID# 222004 | Ft. Pierce | Florida | 34982 | United States |
| University of Miami /ID# 223227 | Miami | Florida | 33136 | United States |
| Triple O Research Institute /ID# 222944 | West Palm Beach | Florida | 33407-3100 | United States |
| Brigham & Women's Hospital /ID# 221847 | Boston | Massachusetts | 02115 | United States |
| Beth Israel Deaconess Medical Center /ID# 222994 | Boston | Massachusetts | 02215-5400 | United States |
| Intermountain Healthcare /ID# 221955 | Salt Lake City | Utah | 84103 | United States |
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)
| COMPLETED |
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| NOT COMPLETED |
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Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | 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) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Race/Ethnicity, Customized | Count of Participants | Participants | No |
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| COVID-19 symptom onset duration prior to baseline (days) | Baseline refers to the last non-missing observation on or before the first day of study drug administration. | Mean | Standard Deviation | days |
| ||||||||||||||
| Number of participants with a score of 4 on the WHO-8 ordinal scale at screening | WHO-8 scores: 0 (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). | Count of Participants | Participants | No |
| ||||||||||||||
| Stratification factor of prescription for remdesivir | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage of Participants Alive and Without Respiratory Failure Through Day 28 | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Number | 80% Confidence Interval | percentage of participants | Through Day 28 |
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| Secondary | Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14 | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug; participants with baseline and Day 14 score data | Posted | Count of Participants | Participants | No | At Day 14 |
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| Secondary | Median Reduction in Days Spent on Supplemental Oxygen | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Median | Full Range | days | Up to Day 28 |
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| Secondary | All-Cause Mortality at Study Days 7, 14, 21, and 28 | The percentage of participants with mortality from any cause was recorded. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Number | 80% Confidence Interval | percentage of participants | At Study Days 7, 14, 21, and 28 |
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| Secondary | Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28 | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Number | 80% Confidence Interval | percentage of participants | At Study Days 7, 14, 21, and 28 |
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| Secondary | Mechanical Ventilation-Free Survival | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Median | 95% Confidence Interval | days | Up to Day 28 |
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| Secondary | Days on Mechanical Ventilation | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Median | Full Range | days | Up to Day 28 |
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| Secondary | Median Duration of Hospitalization | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Median | Full Range | days | Up to Day 28 |
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| Secondary | Time to Discharge From Hospital | 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. | Full Analysis Set (FAS): all randomized participants who received at least 1 dose of study drug | Posted | Median | Full Range | days | Up to Day 28 |
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| Secondary | Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio | 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). | 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. | Posted | Mean | Standard Deviation | mmHg | At Study Days 7, 14, 21, and 28 |
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| Secondary | Oxygenation Index | 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). | 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. | Posted | Mean | Standard Deviation | units on a scale | At Study Days 7, 14, 21, and 28 |
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| Secondary | Number of Participants With Adverse Events | 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. | Safety Population: all participants who received at least 1 dose of study drug | Posted | Count of Participants | Participants | No | From first dose of study drug until 30 days following last dose of study drug (up to 70 days) |
|
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
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) | 1 | 22 | 4 | 22 | 8 | 22 |
| EG001 | 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) | 1 | 24 | 3 | 24 | 6 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| PNEUMONIA | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| PNEUMONIA BACTERIAL | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| SEPSIS | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| SEPTIC SHOCK | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| STAPHYLOCOCCAL BACTERAEMIA | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| ACUTE KIDNEY INJURY | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| ACUTE RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| PULMONARY HAEMORRHAGE | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| PERIPHERAL ARTERY THROMBOSIS | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| NAUSEA | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| HYPERTENSION | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Services | AbbVie | 800-633-9110 | abbvieclinicaltrials@abbvie.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 20, 2021 | Apr 22, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D055370 | Lung Injury |
| D012131 | Respiratory Insufficiency |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D013898 | Thoracic Injuries |
| D014947 | Wounds and Injuries |
| D012120 | Respiration Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C551803 | ibrutinib |
Not provided
Not provided
Not provided
| Male |
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| Black or African American |
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| American Indian or Alaska Native |
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| Native Hawaiian or Other Pacific Islander |
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| Asian |
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| Multiple |
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| Other |
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| Missing |
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| No |
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| The difference in response rates between the experimental arm and the control arm were analyzed using the Miettinen-Nurminen (MN) method, adjusting for the stratification factor of prescription for remdesivir. The MN test p-value for testing the rate difference = 0 at twosided alpha = 0.2. | Miettinen-Nurminen method | =0.599 | Adjusted risk difference (%) | 5.8 | 2-Sided | 95 | -18.1 | 28.7 | Ibrutinib 420 mg + SOC - Placebo + SOC Miettinen-Nurminen (MN) CI for the adjusted risk difference across strata | Superiority |
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