COVID-19 Pneumonia
Conditions
Brief summary
This is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) compared with placebo and of UTTR1147A compared with placebo, in combination with standard of care (SOC), in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.
Interventions
DRUGMSTT1041A
Participants received one intravenous (IV) infusion of MSTT1041A 700 milligrams (mg) on Day 1. A second IV dose of MSTT1041A 350 mg was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen.
DRUGMSTT1041A-matched Placebo
Participants received up to 2 intravenous infusions of MSTT1041A-matched placebo.
DRUGUTTR1147A
Participants received one intravenous (IV) infusion of UTTR1147A 90 micrograms/kilogram body weight (μg/kg) on Day 1. A second IV dose of UTTR1147A 90 μg/kg was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen.
DRUGUTTR1147A-matched Placebo
Participants received up to 2 intravenous infusions of UTTR1147A-matched placebo.
Sponsors
Biomedical Advanced Research and Development Authority
Genentech, Inc.
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
* Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan * Peripheral capillary oxygen saturation (SpO2) ≤93% (on room air or supplemental oxygen) or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤300 millimetres of mercury (mmHg) or requiring supplemental oxygen to maintain SpO2 \>93% or requirement for supplemental oxygen to maintain SpO2 at an acceptable level per local standard of care
Exclusion criteria
* Pregnant or breastfeeding, or positive pregnancy test at screening * Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study * In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments * Participating in another clinical drug trial * Treatment with investigational therapy (other than for COVID-19) within 5 half-lives or 30 days (whichever is longer) prior to initiation of study drug * Use of Janus kinase (JAK) inhibitor within 30 days or 5 drug elimination half-lives (whichever is longer) prior to screening * Have received high-dose systemic corticosteroids (≥1 mg/kg/day methylprednisolone or equivalent) within 72 hours prior to Day 1 * Known HIV infection with CD4 \<200 cells/microlitre (uL) or \<14% of all lymphocytes * ALT or AST \>10 times the upper limit of normal (ULN) detected at screening * History of anaplastic large-cell lymphoma or mantle-cell lymphoma * History of cancer within the previous 5 years unless it has been adequately treated and considered cured or remission-free in the investigator's judgment * Clinical evidence of active or unstable cardiovascular disease (e.g., acute myocardial ischemia or decompensated heart failure), as determined by investigator assessment, ECG, laboratory assessment, or echocardiographic data * History of moderate or severe allergic, anaphylactic, or anaphylactoid reactions or hypersensitivity to any component of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28 | From Baseline up to 28 days | The time to recovery was defined as the time from baseline to a clinical status score of 1 or 2 on the 7-category ordinal scale (whichever occurs first); clinical status scores are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration of MSTT1041A at Specified Timepoints | For the first dose: at 0.5 hours post-dose on Day 1, on Days 2, 3, 7, and 15; and for the second dose: Days 15 (0.5 hours post-dose), 21, and 28 | — |
| Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28 | From Baseline up to 28 days | The 7 categories of the clinical status ordinal scale are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death |
| Time to Hospital Discharge or Ready for Discharge by Day 28 | Up to 28 days | Hospital discharge is category number 1 out of the 7 categories of the clinical status ordinal scale, and it is defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen). |
| Duration of Supplemental Oxygen by Day 28 | Up to 28 days | Duration of supplemental oxygen was defined as the number of days during the 28-day treatment period when the participant is alive and receives Supplemental Oxygen or other forms of ventilation, as recorded in the Vital Signs and Oxygen Saturation form. For each participant, the duration of multiple non-consecutive periods during which the participant received supplemental oxygen was summed. For any days prior to Day 28 where status of supplemental oxygen use was missing, the last known status was to be carried forward. |
| Percentage of Participants Alive and Free of Respiratory Failure by Day 28 | Up to 28 days | Respiratory failure was defined as requiring non-invasive ventilation, high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation \[ECMO\]). |
| Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale | Day 14 | The clinical status scores of the 7 category ordinal scale are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death |
| Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale | Day 28 | The clinical status scores of the 7 category ordinal scale are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death |
| Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 | Up to 28 days | — |
| Number of Ventilator-Free Days by Day 28 | Up to 28 days | The number of ventilator-free days was defined as the number of days during the 28-day treatment period when the participant is alive and without need for invasive mechanical ventilation. For any day during Day 1 and Day 28, if invasive mechanical ventilation or ECMO was recorded for any part of the day ( \>= 12 hours during mechanical invasive ventilation for patients with tracheostomy), the day was not to be counted as a ventilator-free day; otherwise, the day was to be counted. For any days prior to Day 28 where status of mechanical ventilator was missing, the last known status was to be carried forward. The total number of days was the sum of all ventilator-free days, regardless of whether the days occurred consecutively or in nonconsecutive intervals. |
| Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28 | Up to 28 days | — |
| Serum Concentration of UTTR1147A at Specified Timepoints | For the first dose: at 0.5 hours post-dose on Day 1, on Days 2, 3, 7, and 15; and for the second dose: Days 15 (0.5 hours post-dose), 21, and 28 | — |
| Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First) | Up to 28 days | — |
| Percentage of Participants Who Died by Day 14 | Up to Day 14 | — |
| Percentage of Participants Who Died by Day 28 | Up to Day 28 | — |
| Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours | Up to 28 days | The National Early Warning Score 2 (NEWS2) is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. Its purpose is to identify acutely ill patients. The NEWS2 scoring system measures 7 physiological parameters: respiration rate, peripheral capillary oxygen saturation, breathing air or supplementary oxygen, systolic blood pressure, pulse rate, level of consciousness or new-onset confusion, and body temperature. A score of 0, 1, 2, or 3 is allocated to each parameter (except for air or oxygen, with respective scores of 0 and 2); a higher score means the parameter is further from the normal range. The scores for each parameter are then summed (with an aggregate score ranging from 0 to 20), and a higher aggregate score indicates a worse clinical condition of the patient, thus indicating the need for a more urgent clinical response. |
| Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | From Baseline until study completion/discontinuation (up to 60 days) | The terms severe and serious are not synonymous with respect to an adverse event (AE). Severity refers to the intensity of an AE (rated according to NCI-CTCAE v5.0 criteria or, if not listed, the following scale: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to AE), whereas a serious AE (SAE) is a significant medical event (per standard SAE criteria), such as a life-threatening or fatal AE or an AE that prolongs inpatient hospitalization. Severity and seriousness were independently assessed by the investigator for each AE that was recorded. The investigator also assessed each AE for whether the event was considered to be related to the study drug. |
| Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | From Baseline up to 60 days | Clinical laboratory tests were performed over the course of the study and the grading of any abnormal values outside of the normal range (High or Low) was based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0); the higher the grade, the greater the lab parameter deviated from the normal range. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. SGPT/ALT = alanine aminotransferase; SGOT/AST = aspartate aminotransferase; INR = international normalized ratio; aPTT = activated partial thromboplastin time |
| Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | From Baseline up to 60 days | The number of participants with vital sign abnormalities outside of the normal upper (i.e., High) and lower limits (i.e., Low) were summarized for each parameter. The normal reference range used for each vital sign parameter was as follows: Diastolic Blood Pressure, 50-90 millimetres of mercury (mmHg); Oxygen Saturation, ≥94%; Pulse Rate, 60-100 beats per minute; Respiratory Rate, 8-20 breaths per minute; Systolic Blood Pressure, 90-140 mmHg; Temperature, 36.5-38 degrees Celsius (C). Not every vital sign abnormality qualified as an adverse event. A vital sign result was to be reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgement. |
| Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline, Days 14 and 28, Discharge Day (up to Day 28), and Study Completion Visit (up to Day 60) | Electrocardiogram (ECG) recordings were to be performed after the participant had been resting in a supine position for at least 10 minutes if possible. The investigator's interpretation of the ECG (e.g., normal or abnormal) was recorded. |
| Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | At Baseline (pre-dose on Day 1) and post-baseline (Days 15 and 28; and discharge day and study completion [up to 60 days]) | Serum samples were collected, and participants who received treatment with MSTT1041A or MSTT1041A-matched placebo were assessed for antidrug antibodies (ADAs) to MSTT1041A, while those who received UTTR1147A or UTTR1147A-matched placebo were assessed for ADAs to UTTR1147A. Participants who received placebo treatment were only assessed for the presence of ADAs at baseline. The percentage of ADA-positive participants at baseline (baseline prevalence) and after drug administration (postbaseline incidence) are summarized. When determining postbaseline incidence, participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). |
| Duration of Intensive Care Unit (ICU) Stay by Day 28 | Up to 28 days | Duration of ICU stay was calculated as the total number of hours (expressed in days) spent in ICU up to and inclusive of 28 days. ICU duration was derived from the ICU Stay Information Log using the difference between ICU discharge date/time and ICU admission date/time. If ICU admission occurred before randomization, the ICU duration was to be counted from the date of dosing. Partial admission and discharge date/time were to be imputed following a conservative approach. For each participant, durations of multiple ICU stays were to be summed. |
Countries
Brazil, Mexico, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Placebo Participants randomized to this arm received one intravenous (IV) infusion of either MSTT1041A-matched placebo or UTTR1147A-matched placebo on Day 1. A second IV infusion of either MSTT1041A-matched placebo or UTTR1147A-matched placebo (same placebo as the first infusion) was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia. | 134 |
| MSTT1041A Participants randomized to this arm received one intravenous (IV) infusion of MSTT1041A 700 milligrams (mg) on Day 1. A second IV dose of MSTT1041A 350 mg was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia. | 130 |
| UTTR1147A Participants randomized to this arm received one intravenous (IV) infusion of UTTR1147A 90 micrograms/kilogram body weight (μg/kg) on Day 1. A second IV dose of UTTR1147A 90 μg/kg was given on Day 15 if the participant remained hospitalized with a requirement for supplemental oxygen. Study treatment was given in combination with the standard of care for COVID-19 pneumonia. | 132 |
| Total | 396 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Death | 22 | 22 | 21 |
| Overall Study | Lost to Follow-up | 5 | 8 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 1 |
Baseline characteristics
| Characteristic | Total | All Placebo | UTTR1147A | MSTT1041A |
|---|---|---|---|---|
| Age, Continuous | 57.0 Years STANDARD_DEVIATION 13.1 | 56.0 Years STANDARD_DEVIATION 13.5 | 57.8 Years STANDARD_DEVIATION 12.6 | 57.3 Years STANDARD_DEVIATION 13.4 |
| Clinical Status Score at Baseline Clinical Status Score Not Available | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 2 | 8 Participants | 3 Participants | 1 Participants | 4 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 3 | 153 Participants | 47 Participants | 57 Participants | 49 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 4 | 198 Participants | 71 Participants | 63 Participants | 64 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 5 | 26 Participants | 10 Participants | 8 Participants | 8 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 6 | 9 Participants | 3 Participants | 2 Participants | 4 Participants |
| Clinical Status Score at Baseline Clinical Status Score of 7 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Country of Enrollment Brazil | 59 Participants | 19 Participants | 20 Participants | 20 Participants |
| Country of Enrollment Mexico | 54 Participants | 14 Participants | 17 Participants | 23 Participants |
| Country of Enrollment Spain | 44 Participants | 16 Participants | 15 Participants | 13 Participants |
| Country of Enrollment United States | 239 Participants | 85 Participants | 80 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 219 Participants | 77 Participants | 70 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 164 Participants | 53 Participants | 58 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 4 Participants | 4 Participants | 5 Participants |
| Mechanical Ventilation Required (Yes/No) No Baseline Mechanical Ventilation | 360 Participants | 122 Participants | 121 Participants | 117 Participants |
| Mechanical Ventilation Required (Yes/No) Yes, Baseline Mechanical Ventilation | 36 Participants | 12 Participants | 11 Participants | 13 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 6 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 6 Participants | 5 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 27 Participants | 10 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 5 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 75 Participants | 24 Participants | 27 Participants | 24 Participants |
| Race/Ethnicity, Customized White | 268 Participants | 92 Participants | 89 Participants | 87 Participants |
| Region of Enrollment North America | 293 Participants | 99 Participants | 97 Participants | 97 Participants |
| Region of Enrollment South America | 59 Participants | 19 Participants | 20 Participants | 20 Participants |
| Region of Enrollment Western Europe | 44 Participants | 16 Participants | 15 Participants | 13 Participants |
| Sex: Female, Male Female | 153 Participants | 45 Participants | 52 Participants | 56 Participants |
| Sex: Female, Male Male | 243 Participants | 89 Participants | 80 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 23 / 134 | 23 / 130 | 21 / 132 |
| other Total, other adverse events | 29 / 134 | 42 / 130 | 40 / 132 |
| serious Total, serious adverse events | 38 / 134 | 38 / 130 | 34 / 132 |
Outcome results
Primary
Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28
The time to recovery was defined as the time from baseline to a clinical status score of 1 or 2 on the 7-category ordinal scale (whichever occurs first); clinical status scores are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death.
Time frame: From Baseline up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28 | 10.0 Days |
| MSTT1041A | Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28 | 11.0 Days |
| UTTR1147A | Time to Recovery, Defined as the Time to a Clinical Status Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First) by Day 28 | 10.0 Days |
p-value: 0.926695% CI: [0.75, 1.36]Unstratified Log Rank
p-value: 0.35795% CI: [0.86, 1.54]Unstratified Log Rank
p-value: 0.981295% CI: [0.74, 1.36]Stratified Log Rank
p-value: 0.515195% CI: [0.82, 1.49]Stratified Log Rank
Secondary
Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale
The clinical status scores of the 7 category ordinal scale are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death
Time frame: Day 14
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale | 1.0 Score on a scale |
| MSTT1041A | Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale | 1.0 Score on a scale |
| UTTR1147A | Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale | 1.0 Score on a scale |
p-value: 0.5273Van Elteren
p-value: 0.6515Van Elteren
p-value: 0.547595% CI: [0.71, 1.91]Proportional Odds Model
p-value: 0.565295% CI: [0.71, 1.89]Proportional Odds Model
Secondary
Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale
The clinical status scores of the 7 category ordinal scale are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death
Time frame: Day 28
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale | 1.0 Score on a scale |
| MSTT1041A | Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale | 1.0 Score on a scale |
| UTTR1147A | Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale | 1.0 Score on a scale |
p-value: 0.3401Van Elteren
p-value: 0.4676Van Elteren
p-value: 0.340895% CI: [0.75, 2.29]Proportional Odds Model
p-value: 0.33295% CI: [0.76, 2.29]Proportional Odds Model
Secondary
Duration of Intensive Care Unit (ICU) Stay by Day 28
Duration of ICU stay was calculated as the total number of hours (expressed in days) spent in ICU up to and inclusive of 28 days. ICU duration was derived from the ICU Stay Information Log using the difference between ICU discharge date/time and ICU admission date/time. If ICU admission occurred before randomization, the ICU duration was to be counted from the date of dosing. Partial admission and discharge date/time were to be imputed following a conservative approach. For each participant, durations of multiple ICU stays were to be summed.
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Duration of Intensive Care Unit (ICU) Stay by Day 28 | 3.10 Days |
| MSTT1041A | Duration of Intensive Care Unit (ICU) Stay by Day 28 | 2.62 Days |
| UTTR1147A | Duration of Intensive Care Unit (ICU) Stay by Day 28 | 0.00 Days |
p-value: 0.4845Van Elteren
p-value: 0.057Van Elteren
Secondary
Duration of Supplemental Oxygen by Day 28
Duration of supplemental oxygen was defined as the number of days during the 28-day treatment period when the participant is alive and receives Supplemental Oxygen or other forms of ventilation, as recorded in the Vital Signs and Oxygen Saturation form. For each participant, the duration of multiple non-consecutive periods during which the participant received supplemental oxygen was summed. For any days prior to Day 28 where status of supplemental oxygen use was missing, the last known status was to be carried forward.
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Duration of Supplemental Oxygen by Day 28 | 18.00 Days |
| MSTT1041A | Duration of Supplemental Oxygen by Day 28 | 17.00 Days |
| UTTR1147A | Duration of Supplemental Oxygen by Day 28 | 13.50 Days |
p-value: 0.5304Van Elteren
p-value: 0.5058Van Elteren
Secondary
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints
Electrocardiogram (ECG) recordings were to be performed after the participant had been resting in a supine position for at least 10 minutes if possible. The investigator's interpretation of the ECG (e.g., normal or abnormal) was recorded.
Time frame: Baseline, Days 14 and 28, Discharge Day (up to Day 28), and Study Completion Visit (up to Day 60)
Population: Safety Population: participants who received at least one dose of study drug, with participants grouped according to the treatment received. Only participants with nonmissing assessments at a given timepoint were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Discharge Day - Normal ECG | 37 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 28 - Abnormal ECG | 12 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Normal ECG | 56 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Discharge Day - Abnormal ECG | 27 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 28 - Normal ECG | 3 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline - Abnormal ECG | 56 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 14 - Abnormal ECG | 20 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline - Normal ECG | 76 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Abnormal ECG | 13 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 14 - Normal ECG | 14 Participants |
| All Placebo | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Unable to Evaluate ECG | 0 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 28 - Normal ECG | 2 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline - Abnormal ECG | 60 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline - Normal ECG | 66 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 14 - Abnormal ECG | 13 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 14 - Normal ECG | 16 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 28 - Abnormal ECG | 3 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Discharge Day - Abnormal ECG | 28 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Discharge Day - Normal ECG | 47 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Abnormal ECG | 18 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Normal ECG | 46 Participants |
| MSTT1041A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Unable to Evaluate ECG | 1 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Normal ECG | 40 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Discharge Day - Normal ECG | 39 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 14 - Abnormal ECG | 14 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline - Abnormal ECG | 55 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Abnormal ECG | 21 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Baseline - Normal ECG | 75 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 28 - Normal ECG | 3 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 28 - Abnormal ECG | 4 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Study Completion Visit - Unable to Evaluate ECG | 1 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Discharge Day - Abnormal ECG | 37 Participants |
| UTTR1147A | Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints | Day 14 - Normal ECG | 10 Participants |
Secondary
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline
Clinical laboratory tests were performed over the course of the study and the grading of any abnormal values outside of the normal range (High or Low) was based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0); the higher the grade, the greater the lab parameter deviated from the normal range. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. SGPT/ALT = alanine aminotransferase; SGOT/AST = aspartate aminotransferase; INR = international normalized ratio; aPTT = activated partial thromboplastin time
Time frame: From Baseline up to 60 days
Population: Safety Population: participants who received at least one dose of study drug, with participants grouped according to the treatment received. Only participants with both a baseline assessment and at least one post-baseline assessment per parameter were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 1 | 6 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 4 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 4 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 2 | 11 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 3 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 4 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 1 | 48 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Any Grade | 17 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 3 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 2 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Any Grade | 24 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 4 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 2 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 2 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Any Grade | 47 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 4 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 1 | 14 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 1 | 40 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 3 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Any Grade | 17 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 2 | 4 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 3 | 7 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Grade 2 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 3 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Grade 1 | 10 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Grade 1 | 4 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 4 | 3 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 2 | 6 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Any Grade | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Any Grade | 73 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, High - Grade 2 | 4 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 1 | 43 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 1 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, High - Any Grade | 4 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 2 | 17 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 2 | 3 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 1 | 60 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 3 | 17 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 3 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 3 | 23 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Any Grade | 9 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Any Grade | 12 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 2 | 23 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Grade 1 | 9 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Any Grade | 67 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 1 | 14 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Grade 3 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 3 | 3 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Absolute Count (Abs), Low - Any Grade | 61 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 2 | 6 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Any Grade | 8 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 1 | 12 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 1 | 38 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 1 | 6 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Grade 2 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Any Grade | 77 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 2 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 4 | 3 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Any Grade | 47 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 3 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Uric Acid, High - Any Grade | 33 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 3 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 4 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Uric Acid, High - Grade 3 | 33 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 2 | 9 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Any Grade | 16 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Any Grade | 103 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 4 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 1 | 60 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 1 | 32 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, High - Any Grade | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Any Grade | 71 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 2 | 56 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 3 | 0 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 4 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 3 | 15 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 3 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 3 | 2 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Any Grade | 20 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 2 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 2 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 1 | 14 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Any Grade | 60 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 3 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 1 | 7 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 2 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, High - Grade 1 | 5 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Any Grade | 15 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 3 | 1 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 1 | 11 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Grade 3 | 4 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Grade 2 | 25 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 1 | 34 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Any Grade | 7 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Any Grade | 29 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 2 | 31 Participants |
| All Placebo | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 4 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Any Grade | 6 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 4 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Grade 3 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 3 | 7 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 2 | 26 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Grade 1 | 6 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Grade 2 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 4 | 2 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, High - Any Grade | 2 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 2 | 24 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Any Grade | 39 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 3 | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 3 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Any Grade | 11 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 1 | 6 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 2 | 5 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 3 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 4 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Any Grade | 72 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Any Grade | 105 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 1 | 36 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 2 | 58 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 3 | 11 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Any Grade | 23 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 1 | 22 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 2 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 3 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 1 | 47 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Any Grade | 48 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 1 | 37 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 2 | 7 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 4 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Any Grade | 38 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 1 | 30 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 2 | 5 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 3 | 2 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 4 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 1 | 47 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 2 | 17 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Any Grade | 82 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 3 | 8 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Any Grade | 7 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Grade 1 | 6 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Grade 3 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Absolute Count (Abs), Low - Any Grade | 45 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 1 | 9 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 2 | 17 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 3 | 18 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 4 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, High - Any Grade | 4 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, High - Grade 2 | 4 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Any Grade | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Grade 1 | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Grade 2 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Any Grade | 17 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 1 | 15 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 2 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 3 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 4 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Any Grade | 19 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Grade 2 | 18 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Any Grade | 25 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 1 | 19 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 2 | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 3 | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 4 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Any Grade | 69 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 1 | 61 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 2 | 8 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 3 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Any Grade | 42 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 1 | 35 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 2 | 5 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 3 | 2 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Any Grade | 58 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 1 | 50 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 2 | 6 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 3 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 4 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Any Grade | 16 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 1 | 10 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 2 | 5 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 3 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 4 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Any Grade | 14 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 1 | 9 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 2 | 5 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 3 | 0 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Uric Acid, High - Any Grade | 24 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Uric Acid, High - Grade 3 | 24 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 1 | 1 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 1 | 11 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 3 | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Any Grade | 3 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 2 | 2 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, High - Grade 1 | 2 Participants |
| MSTT1041A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 1 | 8 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 3 | 5 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Any Grade | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 2 | 7 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Any Grade | 84 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Any Grade | 10 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Grade 2 | 23 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 3 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 2 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 1 | 21 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Any Grade | 16 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Grade 1 | 22 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, High - Any Grade | 4 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 1 | 12 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Alkaline Phosphatase, High - Any Grade | 24 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 1 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 2 | 3 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 3 | 12 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 2 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 3 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 2 | 66 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 2 | 29 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, High - Grade 4 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Grade 1 | 40 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 3 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Any Grade | 75 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Albumin, Low - Any Grade | 118 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 3 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 1 | 67 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Grade 2 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 2 | 6 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 3 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Grade 3 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | INR, High - Grade 3 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 2 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Any Grade | 42 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Any Grade | 12 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 4 | 3 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 1 | 36 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Uric Acid, High - Grade 3 | 22 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 2 | 3 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 3 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Any Grade | 11 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | aPTT, High - Grade 3 | 3 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Glucose, Low - Grade 1 | 9 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Total Leukocyte Count, Low - Grade 1 | 10 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Any Grade | 58 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Grade 3 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Fibrinogen, Low - Grade 2 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Absolute Count (Abs), Low - Any Grade | 48 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Grade 1 | 5 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Uric Acid, High - Any Grade | 22 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 1 | 11 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, High - Any Grade | 5 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 1 | 51 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 2 | 23 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 3 | 11 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 3 | 5 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 3 | 11 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 1 | 8 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, Low - Grade 4 | 3 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 1 | 46 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 2 | 7 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, High - Any Grade | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Any Grade | 78 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 2 | 15 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Lymphocytes, Abs, High - Grade 2 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 4 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 3 | 4 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Any Grade | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 3 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 3 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Grade 1 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 2 | 4 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Any Grade | 29 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Neutrophils, Total (Abs), Low - Grade 2 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Grade 1 | 36 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Hemoglobin, Low - Grade 2 | 21 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Any Grade | 12 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGOT/AST, High - Any Grade | 44 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, Low - Grade 4 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 1 | 9 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, High - Grade 1 | 4 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 2 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Grade 1 | 47 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Bilirubin, High - Grade 2 | 2 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 3 | 0 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | SGPT/ALT, High - Any Grade | 60 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Sodium, High - Any Grade | 23 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Platelets, Low - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Calcium, Low - Grade 1 | 48 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Creatinine, High - Grade 4 | 1 Participants |
| UTTR1147A | Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline | Potassium, Low - Any Grade | 25 Participants |
Secondary
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline
The number of participants with vital sign abnormalities outside of the normal upper (i.e., High) and lower limits (i.e., Low) were summarized for each parameter. The normal reference range used for each vital sign parameter was as follows: Diastolic Blood Pressure, 50-90 millimetres of mercury (mmHg); Oxygen Saturation, ≥94%; Pulse Rate, 60-100 beats per minute; Respiratory Rate, 8-20 breaths per minute; Systolic Blood Pressure, 90-140 mmHg; Temperature, 36.5-38 degrees Celsius (C). Not every vital sign abnormality qualified as an adverse event. A vital sign result was to be reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgement.
Time frame: From Baseline up to 60 days
Population: Safety Population: participants who received at least one dose of study drug, with participants grouped according to the treatment received. Only participants with both a baseline assessment and at least one post-baseline assessment were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Systolic Blood Pressure - Low | 20 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Pulse Rate - High | 75 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Temperature - Low | 116 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Respiratory Rate - High | 108 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Respiratory Rate - Low | 1 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Diastolic Blood Pressure - Low | 23 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Oxygen Saturation - Low | 112 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Diastolic Blood Pressure - High | 39 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Systolic Blood Pressure - High | 77 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Pulse Rate - Low | 66 Participants |
| All Placebo | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Temperature - High | 13 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Respiratory Rate - Low | 0 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Diastolic Blood Pressure - Low | 23 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Diastolic Blood Pressure - High | 43 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Oxygen Saturation - Low | 107 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Pulse Rate - Low | 66 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Pulse Rate - High | 62 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Respiratory Rate - High | 104 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Systolic Blood Pressure - Low | 11 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Systolic Blood Pressure - High | 81 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Temperature - Low | 113 Participants |
| MSTT1041A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Temperature - High | 10 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Temperature - Low | 113 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Systolic Blood Pressure - Low | 17 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Oxygen Saturation - Low | 105 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Diastolic Blood Pressure - Low | 21 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Systolic Blood Pressure - High | 70 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Diastolic Blood Pressure - High | 39 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Respiratory Rate - Low | 2 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Pulse Rate - High | 57 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Temperature - High | 14 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Respiratory Rate - High | 103 Participants |
| UTTR1147A | Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline | Pulse Rate - Low | 61 Participants |
Secondary
Number of Ventilator-Free Days by Day 28
The number of ventilator-free days was defined as the number of days during the 28-day treatment period when the participant is alive and without need for invasive mechanical ventilation. For any day during Day 1 and Day 28, if invasive mechanical ventilation or ECMO was recorded for any part of the day ( \>= 12 hours during mechanical invasive ventilation for patients with tracheostomy), the day was not to be counted as a ventilator-free day; otherwise, the day was to be counted. For any days prior to Day 28 where status of mechanical ventilator was missing, the last known status was to be carried forward. The total number of days was the sum of all ventilator-free days, regardless of whether the days occurred consecutively or in nonconsecutive intervals.
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Number of Ventilator-Free Days by Day 28 | 28.0 Days |
| MSTT1041A | Number of Ventilator-Free Days by Day 28 | 28.0 Days |
| UTTR1147A | Number of Ventilator-Free Days by Day 28 | 28.0 Days |
p-value: 0.8007Van Elteren
p-value: 0.8633Van Elteren
Secondary
Percentage of Participants Alive and Free of Respiratory Failure by Day 28
Respiratory failure was defined as requiring non-invasive ventilation, high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation \[ECMO\]).
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Placebo | Percentage of Participants Alive and Free of Respiratory Failure by Day 28 | 38.1 Percentage of participants |
| MSTT1041A | Percentage of Participants Alive and Free of Respiratory Failure by Day 28 | 39.2 Percentage of participants |
| UTTR1147A | Percentage of Participants Alive and Free of Respiratory Failure by Day 28 | 40.2 Percentage of participants |
p-value: 0.845195% CI: [0.64, 1.72]Chi-squared
p-value: 0.726795% CI: [0.67, 1.79]Chi-squared
p-value: 0.845895% CI: [0.63, 1.79]Cochran-Mantel-Haenszel
p-value: 0.790795% CI: [0.64, 1.81]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Placebo | Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 | 24.6 Percentage of participants |
| MSTT1041A | Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 | 28.5 Percentage of participants |
| UTTR1147A | Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 | 24.2 Percentage of participants |
95% CI: [-7.57, 15.24]
95% CI: [-11.46, 10.7]
p-value: 0.480495% CI: [0.7, 2.1]Chi-squared
p-value: 0.941895% CI: [0.56, 1.71]Chi-squared
p-value: 0.498895% CI: [0.68, 2.44]Cochran-Mantel-Haenszel
p-value: 0.904395% CI: [0.54, 1.96]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Died by Day 14
Time frame: Up to Day 14
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Placebo | Percentage of Participants Who Died by Day 14 | 6.0 Percentage of participants |
| MSTT1041A | Percentage of Participants Who Died by Day 14 | 8.5 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Died by Day 14 | 8.3 Percentage of participants |
95% CI: [-4.51, 9.49]
95% CI: [-4.58, 9.31]
p-value: 0.433695% CI: [0.57, 3.74]Chi-squared
p-value: 0.454395% CI: [0.56, 3.68]Chi-squared
p-value: 0.4995% CI: [0.54, 3.97]Cochran-Mantel-Haenszel
p-value: 0.359595% CI: [0.58, 4.28]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Died by Day 28
Time frame: Up to Day 28
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Placebo | Percentage of Participants Who Died by Day 28 | 11.2 Percentage of participants |
| MSTT1041A | Percentage of Participants Who Died by Day 28 | 14.6 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Died by Day 28 | 12.9 Percentage of participants |
95% CI: [-5.42, 12.26]
95% CI: [-6.89, 10.26]
p-value: 0.406795% CI: [0.66, 2.8]Chi-squared
p-value: 0.672895% CI: [0.56, 2.46]Chi-squared
p-value: 0.549595% CI: [0.62, 2.87]Cochran-Mantel-Haenszel
p-value: 0.555195% CI: [0.57, 2.71]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline
Serum samples were collected, and participants who received treatment with MSTT1041A or MSTT1041A-matched placebo were assessed for antidrug antibodies (ADAs) to MSTT1041A, while those who received UTTR1147A or UTTR1147A-matched placebo were assessed for ADAs to UTTR1147A. Participants who received placebo treatment were only assessed for the presence of ADAs at baseline. The percentage of ADA-positive participants at baseline (baseline prevalence) and after drug administration (postbaseline incidence) are summarized. When determining postbaseline incidence, participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response).
Time frame: At Baseline (pre-dose on Day 1) and post-baseline (Days 15 and 28; and discharge day and study completion [up to 60 days])
Population: The immunogenicity analysis population consisted of all participants with an evaluable baseline ADA sample and/or at least one evaluable post-baseline ADA sample. Participants who received placebo treatment were only assessed for the presence of ADAs at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Placebo | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | ADA Positive at Baseline | 3.4 Percentage of participants |
| MSTT1041A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | Treatment-Induced ADA Positive Post-Baseline | 1.9 Percentage of participants |
| MSTT1041A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | ADA Positive at Baseline | 2.6 Percentage of participants |
| MSTT1041A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | Treatment-Enhanced ADA Positive Post-Baseline | 1.0 Percentage of participants |
| MSTT1041A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | ADA Positive Post-Baseline (Total) | 2.9 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | ADA Positive at Baseline | 1.7 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | Treatment-Enhanced ADA Positive Post-Baseline | 0.0 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | ADA Positive at Baseline | 1.6 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | ADA Positive Post-Baseline (Total) | 0.9 Percentage of participants |
| UTTR1147A | Percentage of Participants Who Tested Positive for Anti-Drug Antibodies (ADAs) to MSTT1041A and UTTR1147A at Baseline and at Anytime Post-Baseline | Treatment-Induced ADA Positive Post-Baseline | 0.9 Percentage of participants |
Secondary
Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Placebo | Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28 | 58.2 Percentage of participants |
| MSTT1041A | Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28 | 54.6 Percentage of participants |
| UTTR1147A | Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28 | 46.2 Percentage of participants |
95% CI: [-16.31, 9.12]
95% CI: [-24.67, 0.67]
p-value: 0.55695% CI: [0.53, 1.41]Chi-squared
p-value: 0.050295% CI: [0.38, 1]Chi-squared
p-value: 0.700295% CI: [0.51, 1.6]Cochran-Mantel-Haenszel
p-value: 0.044895% CI: [0.32, 0.99]Cochran-Mantel-Haenszel
Secondary
Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
The terms severe and serious are not synonymous with respect to an adverse event (AE). Severity refers to the intensity of an AE (rated according to NCI-CTCAE v5.0 criteria or, if not listed, the following scale: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to AE), whereas a serious AE (SAE) is a significant medical event (per standard SAE criteria), such as a life-threatening or fatal AE or an AE that prolongs inpatient hospitalization. Severity and seriousness were independently assessed by the investigator for each AE that was recorded. The investigator also assessed each AE for whether the event was considered to be related to the study drug.
Time frame: From Baseline until study completion/discontinuation (up to 60 days)
Population: Safety Population: participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Dose Modification/Interruption | 0 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE | 15 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE Leading to Withdrawal from Treatment | 0 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE Leading to Dose Modification/Interruption | 0 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 3-5 AE | 43 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 87 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | SAE Leading to Withdrawal from Treatment | 2 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related SAE | 0 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | SAE Leading to Dose Modification/Interruption | 0 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE with Fatal Outcome | 23 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal from Treatment | 4 Participants |
| All Placebo | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE (SAE) | 38 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 85 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal from Treatment | 3 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE | 12 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Dose Modification/Interruption | 0 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | SAE Leading to Withdrawal from Treatment | 2 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE Leading to Withdrawal from Treatment | 0 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related SAE | 2 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE Leading to Dose Modification/Interruption | 0 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE (SAE) | 38 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE with Fatal Outcome | 23 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 3-5 AE | 46 Participants |
| MSTT1041A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | SAE Leading to Dose Modification/Interruption | 0 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 3-5 AE | 41 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | SAE Leading to Dose Modification/Interruption | 0 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 95 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE with Fatal Outcome | 21 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE (SAE) | 34 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | SAE Leading to Withdrawal from Treatment | 1 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE Leading to Withdrawal from Treatment | 1 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related SAE | 3 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal from Treatment | 3 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Dose Modification/Interruption | 0 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE | 25 Participants |
| UTTR1147A | Safety Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Related AE Leading to Dose Modification/Interruption | 0 Participants |
Secondary
Serum Concentration of MSTT1041A at Specified Timepoints
Time frame: For the first dose: at 0.5 hours post-dose on Day 1, on Days 2, 3, 7, and 15; and for the second dose: Days 15 (0.5 hours post-dose), 21, and 28
Population: The Pharmacokinetics (PK) analysis population for MSTT1041A consisted of participants who received at least one dose of MSTT1041A and had at least one evaluable PK concentration data point. The PK analysis population is further divided into three groups: participants who only received the first dose, participants who received both doses, and all participants who received the first dose only or both doses (from Days 1 to 15).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Placebo | Serum Concentration of MSTT1041A at Specified Timepoints | Day 1, 0.5 hours post-dose | 206 micrograms per millilitre (μg/mL) | Standard Deviation 71.1 |
| All Placebo | Serum Concentration of MSTT1041A at Specified Timepoints | Day 7 | 88.6 micrograms per millilitre (μg/mL) | Standard Deviation 32.3 |
| All Placebo | Serum Concentration of MSTT1041A at Specified Timepoints | Day 3 | 147 micrograms per millilitre (μg/mL) | Standard Deviation 40.1 |
| All Placebo | Serum Concentration of MSTT1041A at Specified Timepoints | Day 15, pre-dose | 32.2 micrograms per millilitre (μg/mL) | Standard Deviation 15.2 |
| All Placebo | Serum Concentration of MSTT1041A at Specified Timepoints | Day 2 | 175 micrograms per millilitre (μg/mL) | Standard Deviation 49.1 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 21 | 45.4 micrograms per millilitre (μg/mL) | Standard Deviation 20.8 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 1, 0.5 hours post-dose | 227 micrograms per millilitre (μg/mL) | Standard Deviation 66.7 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 2 | 178 micrograms per millilitre (μg/mL) | Standard Deviation 54.3 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 3 | 135 micrograms per millilitre (μg/mL) | Standard Deviation 41 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 7 | 83.9 micrograms per millilitre (μg/mL) | Standard Deviation 28.1 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 15, pre-dose | 33.8 micrograms per millilitre (μg/mL) | Standard Deviation 17.2 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 15, 0.5 hours post-dose | 144 micrograms per millilitre (μg/mL) | Standard Deviation 48 |
| MSTT1041A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 28 | 22.5 micrograms per millilitre (μg/mL) | Standard Deviation 9.17 |
| UTTR1147A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 1, 0.5 hours post-dose | 210 micrograms per millilitre (μg/mL) | Standard Deviation 70.4 |
| UTTR1147A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 3 | 144 micrograms per millilitre (μg/mL) | Standard Deviation 40.4 |
| UTTR1147A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 2 | 176 micrograms per millilitre (μg/mL) | Standard Deviation 50 |
| UTTR1147A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 15, pre-dose | 33.5 micrograms per millilitre (μg/mL) | Standard Deviation 16.6 |
| UTTR1147A | Serum Concentration of MSTT1041A at Specified Timepoints | Day 7 | 87.1 micrograms per millilitre (μg/mL) | Standard Deviation 30.9 |
Secondary
Serum Concentration of UTTR1147A at Specified Timepoints
Time frame: For the first dose: at 0.5 hours post-dose on Day 1, on Days 2, 3, 7, and 15; and for the second dose: Days 15 (0.5 hours post-dose), 21, and 28
Population: The Pharmacokinetics (PK) analysis population for UTTR1147A consisted of participants who received at least one dose of UTTR1147A and had at least one evaluable PK concentration data point. The PK analysis population is further divided into three groups: participants who only received the first dose, participants who received both doses, and all participants who received the first dose only or both doses (from Days 1 to 15).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 2 | 707 nanograms per millilitre (ng/mL) | Standard Deviation 268 |
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 21 | 2.69 nanograms per millilitre (ng/mL) | — |
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 7 | 258 nanograms per millilitre (ng/mL) | Standard Deviation 110 |
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 1, 0.5 hours post-dose | 1260 nanograms per millilitre (ng/mL) | Standard Deviation 568 |
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 15, pre-dose | 42.3 nanograms per millilitre (ng/mL) | Standard Deviation 27.8 |
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 28 | 11.3 nanograms per millilitre (ng/mL) | Standard Deviation 8.89 |
| All Placebo | Serum Concentration of UTTR1147A at Specified Timepoints | Day 3 | 518 nanograms per millilitre (ng/mL) | Standard Deviation 221 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 28 | 173 nanograms per millilitre (ng/mL) | Standard Deviation 78.4 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 1, 0.5 hours post-dose | 1600 nanograms per millilitre (ng/mL) | Standard Deviation 1820 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 2 | 674 nanograms per millilitre (ng/mL) | Standard Deviation 372 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 3 | 604 nanograms per millilitre (ng/mL) | Standard Deviation 222 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 7 | 259 nanograms per millilitre (ng/mL) | Standard Deviation 109 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 15, pre-dose | 88.1 nanograms per millilitre (ng/mL) | Standard Deviation 40.6 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 15, 0.5 hours post-dose | 1410 nanograms per millilitre (ng/mL) | Standard Deviation 802 |
| MSTT1041A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 21 | 297 nanograms per millilitre (ng/mL) | Standard Deviation 147 |
| UTTR1147A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 2 | 700 nanograms per millilitre (ng/mL) | Standard Deviation 290 |
| UTTR1147A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 3 | 537 nanograms per millilitre (ng/mL) | Standard Deviation 223 |
| UTTR1147A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 7 | 258 nanograms per millilitre (ng/mL) | Standard Deviation 109 |
| UTTR1147A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 1, 0.5 hours post-dose | 1320 nanograms per millilitre (ng/mL) | Standard Deviation 952 |
| UTTR1147A | Serum Concentration of UTTR1147A at Specified Timepoints | Day 15, pre-dose | 81.8 nanograms per millilitre (ng/mL) | Standard Deviation 41.9 |
Secondary
Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First)
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First) | NA Days |
| MSTT1041A | Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First) | NA Days |
| UTTR1147A | Time to Clinical Failure by Day 28, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First) | NA Days |
p-value: 0.445695% CI: [0.76, 1.88]Unstratified Log Rank
p-value: 0.721395% CI: [0.57, 1.48]Unstratified Log Rank
p-value: 0.396395% CI: [0.77, 1.96]Stratified Log Rank
p-value: 0.917495% CI: [0.6, 1.58]Stratified Log Rank
Secondary
Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours
The National Early Warning Score 2 (NEWS2) is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. Its purpose is to identify acutely ill patients. The NEWS2 scoring system measures 7 physiological parameters: respiration rate, peripheral capillary oxygen saturation, breathing air or supplementary oxygen, systolic blood pressure, pulse rate, level of consciousness or new-onset confusion, and body temperature. A score of 0, 1, 2, or 3 is allocated to each parameter (except for air or oxygen, with respective scores of 0 and 2); a higher score means the parameter is further from the normal range. The scores for each parameter are then summed (with an aggregate score ranging from 0 to 20), and a higher aggregate score indicates a worse clinical condition of the patient, thus indicating the need for a more urgent clinical response.
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours | 5.5 Days |
| MSTT1041A | Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours | 6.0 Days |
| UTTR1147A | Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours | 6.0 Days |
p-value: 0.383195% CI: [0.71, 2.4]Unstratified Log Rank
p-value: 0.592595% CI: [0.65, 2.15]Unstratified Log Rank
p-value: 0.748795% CI: [0.6, 2.05]Stratified Log Rank
p-value: 0.609295% CI: [0.63, 2.21]Stratified Log Rank
Secondary
Time to Hospital Discharge or Ready for Discharge by Day 28
Hospital discharge is category number 1 out of the 7 categories of the clinical status ordinal scale, and it is defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen).
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Time to Hospital Discharge or Ready for Discharge by Day 28 | 10.0 Days |
| MSTT1041A | Time to Hospital Discharge or Ready for Discharge by Day 28 | 11.0 Days |
| UTTR1147A | Time to Hospital Discharge or Ready for Discharge by Day 28 | 10.0 Days |
p-value: 0.471195% CI: [0.83, 1.49]Unstratified Log Rank
p-value: 0.313595% CI: [0.87, 1.56]Unstratified Log Rank
p-value: 0.573595% CI: [0.81, 1.48]Stratified Log Rank
p-value: 0.597395% CI: [0.8, 1.46]Stratified Log Rank
Secondary
Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28
The 7 categories of the clinical status ordinal scale are defined as follows: 1. Discharged (or ready for discharge as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤2 Litres supplemental oxygen); 2. Non-Intensive Care Unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen; 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen; 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen; 5. ICU, requiring intubation and mechanical ventilation; 6. ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy); 7. Death
Time frame: From Baseline up to 28 days
Population: Modified Intent-to-Treat (mITT) Population: all participants randomized in the study who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Placebo | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28 | 10.0 Days |
| MSTT1041A | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28 | 11.0 Days |
| UTTR1147A | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status by Day 28 | 10.0 Days |
p-value: 0.837395% CI: [0.77, 1.39]Unstratified Log Rank
p-value: 0.339695% CI: [0.86, 1.55]Unstratified Log Rank
p-value: 0.861995% CI: [0.76, 1.39]Stratified Log Rank
p-value: 0.491395% CI: [0.82, 1.5]Stratified Log Rank