COVID-19, SARS-CoV-2
Conditions
Keywords
Coronavirus disease 2019 (COVID-19), Coronavirus, Coronavirus infections, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Brief summary
The purpose of this study is to evaluate the efficacy and safety of intravenous abatacept administered to hospitalized COVID-19 participants with respiratory compromise.
Interventions
BIOLOGICALAbatacept
Specified dose on specified days
OTHERPlacebo
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A confirmed virological diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (by reverse-transcription polymerase chain reaction (RT-PCR)). * Hospitalized (or in the Emergency Department awaiting a bed after hospitalization) * Respiratory compromise as defined by requirement of oxygen supplementation to maintain oxygen saturation ≥ 93% but not requiring mechanical ventilation * Abnormal chest X-ray consistent with COVID-19 and not indicating other serious medical condition that would serve as an exclusionary criteria * Women and men must agree to follow specific methods of contraception, if applicable
Exclusion criteria
* Women who are breastfeeding * Recent acute infection defined as: i) Any acute infection within 60 days prior to randomization that required hospitalization or treatment with parenteral antibiotics (not COVID-19 related) ii) Any acute infection within 30 days prior to randomization that required oral antimicrobial or antiviral therapy * History of chronic or recurrent bacterial infection (e.g., chronic pyelonephritis, osteomyelitis, bronchiectasis) * Prior exposure to BMS-188667 (abatacept) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants on Invasive Mechanical Ventilation or Died Prior to or on Day 28 | From first dose to 28 days post first dose | The percentage of participants on invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal tube (or tracheostomy) or death prior to or on day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died | From first dose to 28 days post first dose | Percentage of participants who died due to any cause. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 1\) Death |
| Percentage of Participants Alive and Free of Respiratory Failure on Day 28±3 | Day 28±3 | Respiratory failure is defined by the type of resources required as defined by the use of any of these: Mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or oxygen delivery by noninvasive positive pressure or high flow nasal cannula. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 4\) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitation on activities |
| Percentage of Participants Returned to Room Air on Day 28 | Day 28 | Recovery of pulmonary function is assessed by the percentage of participants returned to room air on day 28 after they were oxygen dependent and dependence on oxygen has been noted to be prolonged even after hospital discharge. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 5\) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 8) Not hospitalized, no limitation on activities |
| Adjusted Mean Change From Baseline in the Ordinal 8-Point Clinical Status Scale on Day 28 | Baseline and on Day 28 | Adjusted mean change from baseline based on the following Ordinal 8-point Clinical Status Scale that was proposed for the National Institute of Allergy and Infectious Diseases (NIAID) Adaptive COVID-19 Treatment Trial (ACTT) and is recorded by the worst score (lowest number) state for each day: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive mechanical ventilation or high-flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitation on activities Baseline is defined as the last assessment done prior or on Day 1 |
| Percentage of Participants With Serious Adverse Events | From first dose to 60 days post first dose | Percentage of participants with serious adverse events (SAEs). SAE is defined as any untoward medical occurrence that, at any dose: * Results in death * Is life threatening * Requires inpatient hospitalization * Results in persistent or significant disability * Is a congenital anomaly/birth defect * Is an important medical event |
| Percentage of Participants With Serious Adverse Events (SAEs) of the Infections and Infestations System Organ Class | From first dose to 60 days post first dose | Percentage of participants with Serious Adverse Events (SAEs) of the infections and infestations System Organ Class (SOC) |
| Percentage of Participants Alive and Discharged From the Hospital by Day 28 | From day 1 up to day 28 | Percentage of participants alive and discharged from the hospital on day 28. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 7\) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitation on activities |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abatacept Abatacept 10 mg/kg IV + Standard of care (SOC) | 42 |
| Placebo Placebo infusion + Standard of care (SOC) | 19 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-treatment | Other reasons | 2 | 0 |
| Treatment | Death | 5 | 2 |
| Treatment | Hospital discharge | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Abatacept |
|---|---|---|---|
| Age, Continuous | 60.7 Years STANDARD_DEVIATION 14.48 | 61.0 Years STANDARD_DEVIATION 14.17 | 61.1 Years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 32 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 29 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 13 Participants | 9 Participants |
| Race (NIH/OMB) White | 10 Participants | 38 Participants | 28 Participants |
| Sex: Female, Male Female | 6 Participants | 19 Participants | 13 Participants |
| Sex: Female, Male Male | 13 Participants | 42 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 42 | 5 / 19 |
| other Total, other adverse events | 8 / 40 | 10 / 19 |
| serious Total, serious adverse events | 8 / 40 | 6 / 19 |
Outcome results
Primary
Percentage of Participants on Invasive Mechanical Ventilation or Died Prior to or on Day 28
The percentage of participants on invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal tube (or tracheostomy) or death prior to or on day 28.
Time frame: From first dose to 28 days post first dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants on Invasive Mechanical Ventilation or Died Prior to or on Day 28 | 30.0 Percentage of participants |
| Placebo | Percentage of Participants on Invasive Mechanical Ventilation or Died Prior to or on Day 28 | 31.6 Percentage of participants |
p-value: 0.929795% CI: [0.26, 4.49]Cochran-Mantel-Haenszel Chi-Square test
Secondary
Adjusted Mean Change From Baseline in the Ordinal 8-Point Clinical Status Scale on Day 28
Adjusted mean change from baseline based on the following Ordinal 8-point Clinical Status Scale that was proposed for the National Institute of Allergy and Infectious Diseases (NIAID) Adaptive COVID-19 Treatment Trial (ACTT) and is recorded by the worst score (lowest number) state for each day: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive mechanical ventilation or high-flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitation on activities Baseline is defined as the last assessment done prior or on Day 1
Time frame: Baseline and on Day 28
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept | Adjusted Mean Change From Baseline in the Ordinal 8-Point Clinical Status Scale on Day 28 | 3.20 Score on a scale | Standard Error 0.395 |
| Placebo | Adjusted Mean Change From Baseline in the Ordinal 8-Point Clinical Status Scale on Day 28 | 2.56 Score on a scale | Standard Error 0.528 |
p-value: 0.7495% CI: [-0.55, 1.82]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Alive and Discharged From the Hospital by Day 28
Percentage of participants alive and discharged from the hospital on day 28. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 7\) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitation on activities
Time frame: From day 1 up to day 28
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants Alive and Discharged From the Hospital by Day 28 | 82.5 Percentage of participants |
| Placebo | Percentage of Participants Alive and Discharged From the Hospital by Day 28 | 73.7 Percentage of participants |
p-value: 0.473495% CI: [0.33, 12.64]Cochran-Mantel-Haenszel
95% CI: [-16.71, 27.57]
Secondary
Percentage of Participants Alive and Free of Respiratory Failure on Day 28±3
Respiratory failure is defined by the type of resources required as defined by the use of any of these: Mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or oxygen delivery by noninvasive positive pressure or high flow nasal cannula. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 4\) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitation on activities
Time frame: Day 28±3
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants Alive and Free of Respiratory Failure on Day 28±3 | 75.0 Percentage of participants |
| Placebo | Percentage of Participants Alive and Free of Respiratory Failure on Day 28±3 | 73.7 Percentage of participants |
p-value: 0.850495% CI: [0.18, 3.97]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Returned to Room Air on Day 28
Recovery of pulmonary function is assessed by the percentage of participants returned to room air on day 28 after they were oxygen dependent and dependence on oxygen has been noted to be prolonged even after hospital discharge. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 5\) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 8) Not hospitalized, no limitation on activities
Time frame: Day 28
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants Returned to Room Air on Day 28 | 70.0 Percentage of participants |
| Placebo | Percentage of Participants Returned to Room Air on Day 28 | 57.9 Percentage of participants |
p-value: 0.272495% CI: [0.53, 9.82]Cochran-Mantel-Haenszel
95% CI: [-10.61, 36.17]
Secondary
Percentage of Participants Who Died
Percentage of participants who died due to any cause. Participants in the following Ordinal 8-point Clinical Status Scale that is recorded by the worst score (lowest number) state for each day meet this definition: 1\) Death
Time frame: From first dose to 28 days post first dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants Who Died | 12.5 Percentage of participants |
| Placebo | Percentage of Participants Who Died | 15.8 Percentage of participants |
p-value: 0.968495% CI: [-20.55, 20.34]Cochran-Mantel-Haenszel Chi-Square test
Secondary
Percentage of Participants With Serious Adverse Events
Percentage of participants with serious adverse events (SAEs). SAE is defined as any untoward medical occurrence that, at any dose: * Results in death * Is life threatening * Requires inpatient hospitalization * Results in persistent or significant disability * Is a congenital anomaly/birth defect * Is an important medical event
Time frame: From first dose to 60 days post first dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants With Serious Adverse Events | 20.0 Percentage of participants |
| Placebo | Percentage of Participants With Serious Adverse Events | 31.6 Percentage of participants |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs) of the Infections and Infestations System Organ Class
Percentage of participants with Serious Adverse Events (SAEs) of the infections and infestations System Organ Class (SOC)
Time frame: From first dose to 60 days post first dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Percentage of Participants With Serious Adverse Events (SAEs) of the Infections and Infestations System Organ Class | 7.5 Percentage of participants |
| Placebo | Percentage of Participants With Serious Adverse Events (SAEs) of the Infections and Infestations System Organ Class | 5.3 Percentage of participants |