Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia (NCT NCT04386616)

Last Updated: 2022-01-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

396 participants

Primary outcome timeframe

From Baseline up to 28 days

Results posted on

2022-01-10

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	134	130	132
Overall Study Received at Least One Dose of Study Drug	134	130	132
Overall Study Completed Both Doses of Study Drug at Day 15	31	27	25
Overall Study COMPLETED	104	95	104
Overall Study NOT COMPLETED	30	35	28

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Death	22	22	21
Overall Study Lost to Follow-up	5	8	6
Overall Study Withdrawal by Subject	2	4	1
Overall Study Adverse Event	1	1	0

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	Total n=396 Participants Total of all reporting groups
Age, Continuous	56.0 Years STANDARD_DEVIATION 13.5 • n=5 Participants	57.3 Years STANDARD_DEVIATION 13.4 • n=7 Participants	57.8 Years STANDARD_DEVIATION 12.6 • n=5 Participants	57.0 Years STANDARD_DEVIATION 13.1 • n=4 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	56 Participants n=7 Participants	52 Participants n=5 Participants	153 Participants n=4 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	74 Participants n=7 Participants	80 Participants n=5 Participants	243 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	77 Participants n=5 Participants	72 Participants n=7 Participants	70 Participants n=5 Participants	219 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=5 Participants	53 Participants n=7 Participants	58 Participants n=5 Participants	164 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	10 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	27 Participants n=4 Participants
Race/Ethnicity, Customized White	92 Participants n=5 Participants	87 Participants n=7 Participants	89 Participants n=5 Participants	268 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	24 Participants n=5 Participants	24 Participants n=7 Participants	27 Participants n=5 Participants	75 Participants n=4 Participants
Region of Enrollment North America	99 Participants n=5 Participants	97 Participants n=7 Participants	97 Participants n=5 Participants	293 Participants n=4 Participants
Region of Enrollment South America	19 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	59 Participants n=4 Participants
Region of Enrollment Western Europe	16 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	44 Participants n=4 Participants
Country of Enrollment Brazil	19 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	59 Participants n=4 Participants
Country of Enrollment Mexico	14 Participants n=5 Participants	23 Participants n=7 Participants	17 Participants n=5 Participants	54 Participants n=4 Participants
Country of Enrollment Spain	16 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	44 Participants n=4 Participants
Country of Enrollment United States	85 Participants n=5 Participants	74 Participants n=7 Participants	80 Participants n=5 Participants	239 Participants n=4 Participants
Mechanical Ventilation Required (Yes/No) Yes, Baseline Mechanical Ventilation	12 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	36 Participants n=4 Participants
Mechanical Ventilation Required (Yes/No) No Baseline Mechanical Ventilation	122 Participants n=5 Participants	117 Participants n=7 Participants	121 Participants n=5 Participants	360 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 1	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 2	3 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 3	47 Participants n=5 Participants	49 Participants n=7 Participants	57 Participants n=5 Participants	153 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 4	71 Participants n=5 Participants	64 Participants n=7 Participants	63 Participants n=5 Participants	198 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 5	10 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	26 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 6	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score of 7	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Clinical Status Score at Baseline Clinical Status Score Not Available	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
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 Interval 8.0 to 14.0	11.0 Days Interval 9.0 to 14.0	10.0 Days Interval 8.0 to 13.0	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
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 Interval 8.0 to 14.0	11.0 Days Interval 9.0 to 13.0	10.0 Days Interval 8.0 to 12.0	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Time to Hospital Discharge or "Ready for Discharge" by Day 28	10.0 Days Interval 8.0 to 14.0	11.0 Days Interval 9.0 to 13.0	10.0 Days Interval 8.0 to 13.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Duration of Supplemental Oxygen by Day 28	18.00 Days Interval 13.0 to 27.0	17.00 Days Interval 11.0 to 27.0	13.50 Days Interval 10.0 to 21.0	—

SECONDARY outcome

Timeframe: Up to 28 days

Respiratory failure was defined as requiring non-invasive ventilation, high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation \[ECMO\]).

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Percentage of Participants Alive and Free of Respiratory Failure by Day 28	38.1 Percentage of participants Interval 29.47 to 46.65	39.2 Percentage of participants Interval 30.45 to 48.01	40.2 Percentage of participants Interval 31.41 to 48.89	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Clinical Status Score at Day 14, Assessed Using a 7-Category Ordinal Scale	1.0 Score on a scale Interval 1.0 to 4.0	1.0 Score on a scale Interval 1.0 to 3.0	1.0 Score on a scale Interval 1.0 to 4.0	—

SECONDARY outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Clinical Status Score at Day 28, Assessed Using a 7-Category Ordinal Scale	1.0 Score on a scale Interval 1.0 to 4.0	1.0 Score on a scale Interval 1.0 to 1.0	1.0 Score on a scale Interval 1.0 to 1.0	—

SECONDARY outcome

Timeframe: Up to 28 days

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Percentage of Participants Needing Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Day 28	24.6 Percentage of participants Interval 16.96 to 32.29	28.5 Percentage of participants Interval 20.32 to 36.6	24.2 Percentage of participants Interval 16.55 to 31.93	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Number of Ventilator-Free Days by Day 28	28.0 Days Interval 20.0 to 28.0	28.0 Days Interval 20.0 to 28.0	28.0 Days Interval 23.5 to 28.0	—

SECONDARY outcome

Timeframe: Up to 28 days

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Percentage of Participants With an Intensive Care Unit (ICU) Stay by Day 28	58.2 Percentage of participants Interval 49.48 to 66.93	54.6 Percentage of participants Interval 45.67 to 63.56	46.2 Percentage of participants Interval 37.33 to 55.1	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Duration of Intensive Care Unit (ICU) Stay by Day 28	3.10 Days Interval 0.0 to 5.23	2.62 Days Interval 0.0 to 6.02	0.00 Days Interval 0.0 to 2.14	—

SECONDARY outcome

Timeframe: Up to 28 days

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
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 Interval 13.0 to The median and upper limit of the interquartile range could not be estimated because an insufficient number of clinical failure events had occurred.	NA Days Interval 9.0 to The median and upper limit of the interquartile range could not be estimated because an insufficient number of clinical failure events had occurred.	NA Days The median and lower and upper limits of the interquartile range could not be estimated because an insufficient number of clinical failure events had occurred.	—

SECONDARY outcome

Timeframe: Up to Day 14

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Percentage of Participants Who Died by Day 14	6.0 Percentage of participants Interval 1.59 to 10.35	8.5 Percentage of participants Interval 3.29 to 13.63	8.3 Percentage of participants Interval 3.24 to 13.43	—

SECONDARY outcome

Timeframe: Up to Day 28

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Percentage of Participants Who Died by Day 28	11.2 Percentage of participants Interval 5.48 to 16.91	14.6 Percentage of participants Interval 8.16 to 21.07	12.9 Percentage of participants Interval 6.79 to 18.97	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) Aggregate Score of ≤2 Maintained for 24 Hours	5.5 Days Interval 4.0 to 7.0	6.0 Days Interval 4.0 to 8.0	6.0 Days Interval 3.0 to 9.0	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
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	85 Participants	95 Participants	—
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	23 Participants	21 Participants	—
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	38 Participants	34 Participants	—
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	2 Participants	1 Participants	—
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	0 Participants	0 Participants	—
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	2 Participants	3 Participants	—
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	3 Participants	3 Participants	—
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	0 Participants	0 Participants	—
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	12 Participants	25 Participants	—
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	0 Participants	1 Participants	—
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	0 Participants	0 Participants	—
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	46 Participants	41 Participants	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Alkaline Phosphatase, High - Grade 2	5 Participants	1 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Alkaline Phosphatase, High - Grade 3	1 Participants	0 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, Low - Grade 2	17 Participants	17 Participants	21 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, Low - Grade 3	17 Participants	8 Participants	11 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, High - Any Grade	9 Participants	7 Participants	5 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, High - Grade 1	9 Participants	6 Participants	5 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, High - Grade 3	0 Participants	1 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Absolute Count (Abs), Low - Any Grade	61 Participants	45 Participants	48 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Abs, Low - Grade 1	14 Participants	9 Participants	11 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Abs, Low - Grade 2	23 Participants	17 Participants	23 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Abs, Low - Grade 3	23 Participants	18 Participants	11 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGPT/ALT, High - Any Grade	60 Participants	48 Participants	60 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Abs, Low - Grade 4	1 Participants	1 Participants	3 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Abs, High - Any Grade	4 Participants	4 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Lymphocytes, Abs, High - Grade 2	4 Participants	4 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGPT/ALT, High - Grade 1	48 Participants	37 Participants	47 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Platelets, Low - Any Grade	17 Participants	17 Participants	12 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGPT/ALT, High - Grade 2	5 Participants	7 Participants	7 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Albumin, Low - Any Grade	103 Participants	105 Participants	118 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Albumin, Low - Grade 1	32 Participants	36 Participants	40 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Albumin, Low - Grade 2	56 Participants	58 Participants	66 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Albumin, Low - Grade 3	15 Participants	11 Participants	12 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Alkaline Phosphatase, High - Any Grade	20 Participants	23 Participants	24 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Alkaline Phosphatase, High - Grade 1	14 Participants	22 Participants	22 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGPT/ALT, High - Grade 3	5 Participants	3 Participants	5 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGPT/ALT, High - Grade 4	2 Participants	1 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGOT/AST, High - Any Grade	47 Participants	38 Participants	44 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGOT/AST, High - Grade 1	40 Participants	30 Participants	36 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGOT/AST, High - Grade 2	4 Participants	5 Participants	4 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGOT/AST, High - Grade 3	0 Participants	2 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline SGOT/AST, High - Grade 4	3 Participants	1 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, Low - Any Grade	73 Participants	82 Participants	84 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, Low - Grade 1	34 Participants	47 Participants	48 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, Low - Grade 2	31 Participants	26 Participants	29 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, Low - Grade 3	5 Participants	7 Participants	4 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, Low - Grade 4	3 Participants	2 Participants	3 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, High - Any Grade	5 Participants	2 Participants	4 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Calcium, High - Grade 1	5 Participants	2 Participants	4 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Creatinine, High - Any Grade	24 Participants	39 Participants	29 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Creatinine, High - Grade 1	6 Participants	11 Participants	8 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Creatinine, High - Grade 2	11 Participants	24 Participants	15 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Creatinine, High - Grade 3	7 Participants	3 Participants	5 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Creatinine, High - Grade 4	0 Participants	1 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Fibrinogen, Low - Any Grade	7 Participants	3 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Fibrinogen, Low - Grade 1	1 Participants	1 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Fibrinogen, Low - Grade 2	3 Participants	2 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Fibrinogen, Low - Grade 3	2 Participants	0 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Fibrinogen, Low - Grade 4	1 Participants	0 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Glucose, Low - Any Grade	8 Participants	11 Participants	12 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Glucose, Low - Grade 1	6 Participants	6 Participants	9 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Glucose, Low - Grade 2	1 Participants	5 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, High - Grade 2	5 Participants	3 Participants	3 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Platelets, Low - Grade 1	14 Participants	15 Participants	9 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, High - Grade 3	2 Participants	3 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Platelets, Low - Grade 2	2 Participants	0 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Platelets, Low - Grade 3	1 Participants	1 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Platelets, Low - Grade 4	0 Participants	1 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Glucose, Low - Grade 3	1 Participants	0 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Glucose, Low - Grade 4	0 Participants	0 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, Low - Any Grade	29 Participants	19 Participants	25 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, Low - Any Grade	77 Participants	72 Participants	78 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Hemoglobin, Low - Grade 1	43 Participants	47 Participants	46 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, Low - Grade 2	25 Participants	18 Participants	23 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Neutrophils, Total (Abs), Low - Any Grade	5 Participants	3 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Neutrophils, Total (Abs), Low - Grade 1	4 Participants	3 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, Low - Grade 3	4 Participants	1 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, High - Any Grade	15 Participants	25 Participants	16 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Neutrophils, Total (Abs), Low - Grade 2	1 Participants	0 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, High - Grade 1	7 Participants	19 Participants	12 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline INR, High - Grade 3	2 Participants	0 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline INR, High - Grade 2	9 Participants	8 Participants	6 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Potassium, High - Grade 4	1 Participants	0 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline aPTT, High - Any Grade	47 Participants	42 Participants	42 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline aPTT, High - Grade 1	38 Participants	35 Participants	36 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline INR, High - Any Grade	71 Participants	69 Participants	75 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline INR, High - Grade 1	60 Participants	61 Participants	67 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline aPTT, High - Grade 3	3 Participants	2 Participants	3 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, Low - Any Grade	67 Participants	58 Participants	58 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, Low - Grade 1	60 Participants	50 Participants	51 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, Low - Grade 2	6 Participants	6 Participants	7 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, Low - Grade 3	1 Participants	1 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, Low - Grade 4	0 Participants	1 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, High - Any Grade	17 Participants	16 Participants	23 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, High - Grade 1	11 Participants	10 Participants	21 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, High - Grade 2	5 Participants	5 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, High - Grade 3	0 Participants	1 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Sodium, High - Grade 4	1 Participants	0 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Bilirubin, High - Any Grade	16 Participants	14 Participants	11 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Bilirubin, High - Grade 1	12 Participants	9 Participants	8 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Bilirubin, High - Grade 2	2 Participants	5 Participants	2 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Bilirubin, High - Grade 3	2 Participants	0 Participants	1 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Uric Acid, High - Any Grade	33 Participants	24 Participants	22 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Uric Acid, High - Grade 3	33 Participants	24 Participants	22 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Total Leukocyte Count, Low - Any Grade	12 Participants	6 Participants	10 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Total Leukocyte Count, Low - Grade 1	10 Participants	6 Participants	10 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline Total Leukocyte Count, Low - Grade 2	2 Participants	0 Participants	0 Participants	—
Number of Participants With Clinical Laboratory Test Abnormalities by Highest NCI-CTCAE Grade Post-Baseline aPTT, High - Grade 2	6 Participants	5 Participants	3 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Placebo n=133 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Diastolic Blood Pressure - Low	23 Participants	23 Participants	21 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Diastolic Blood Pressure - High	39 Participants	43 Participants	39 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Oxygen Saturation - Low	112 Participants	107 Participants	105 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Pulse Rate - Low	66 Participants	66 Participants	61 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Pulse Rate - High	75 Participants	62 Participants	57 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Respiratory Rate - Low	1 Participants	0 Participants	2 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Respiratory Rate - High	108 Participants	104 Participants	103 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Systolic Blood Pressure - Low	20 Participants	11 Participants	17 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Systolic Blood Pressure - High	77 Participants	81 Participants	70 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Temperature - Low	116 Participants	113 Participants	113 Participants	—
Number of Participants With Vital Sign Abnormalities at Anytime Post-Baseline Temperature - High	13 Participants	10 Participants	14 Participants	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Placebo n=134 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=132 Participants 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.	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.
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Study Completion Visit - Unable to Evaluate ECG	0 Participants	1 Participants	1 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Baseline - Abnormal ECG	56 Participants	60 Participants	55 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Baseline - Normal ECG	76 Participants	66 Participants	75 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Day 14 - Abnormal ECG	20 Participants	13 Participants	14 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Day 14 - Normal ECG	14 Participants	16 Participants	10 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Day 28 - Abnormal ECG	12 Participants	3 Participants	4 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Day 28 - Normal ECG	3 Participants	2 Participants	3 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Discharge Day - Abnormal ECG	27 Participants	28 Participants	37 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Discharge Day - Normal ECG	37 Participants	47 Participants	39 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Study Completion Visit - Abnormal ECG	13 Participants	18 Participants	21 Participants	—
Number of Participants by the Investigator's Interpretations of Electrocardiogram Recordings at Specified Timepoints Study Completion Visit - Normal ECG	56 Participants	46 Participants	40 Participants	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	All Placebo n=59 Participants 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.	MSTT1041A n=130 Participants 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.	UTTR1147A n=59 Participants 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.	UTTR1147A n=132 Participants 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.
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	2.6 Percentage of participants	1.7 Percentage of participants	1.6 Percentage of participants
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	—	0.9 Percentage of participants
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	—	0.9 Percentage of participants
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	—	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	All Placebo n=105 Participants 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.	MSTT1041A n=25 Participants 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.	UTTR1147A n=130 Participants 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.	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.
Serum Concentration of UTTR1147A at Specified Timepoints Day 1, 0.5 hours post-dose	1260 nanograms per millilitre (ng/mL) Standard Deviation 568	1600 nanograms per millilitre (ng/mL) Standard Deviation 1820	1320 nanograms per millilitre (ng/mL) Standard Deviation 952	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 2	707 nanograms per millilitre (ng/mL) Standard Deviation 268	674 nanograms per millilitre (ng/mL) Standard Deviation 372	700 nanograms per millilitre (ng/mL) Standard Deviation 290	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 3	518 nanograms per millilitre (ng/mL) Standard Deviation 221	604 nanograms per millilitre (ng/mL) Standard Deviation 222	537 nanograms per millilitre (ng/mL) Standard Deviation 223	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 7	258 nanograms per millilitre (ng/mL) Standard Deviation 110	259 nanograms per millilitre (ng/mL) Standard Deviation 109	258 nanograms per millilitre (ng/mL) Standard Deviation 109	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 15, pre-dose	42.3 nanograms per millilitre (ng/mL) Standard Deviation 27.8	88.1 nanograms per millilitre (ng/mL) Standard Deviation 40.6	81.8 nanograms per millilitre (ng/mL) Standard Deviation 41.9	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 15, 0.5 hours post-dose	—	1410 nanograms per millilitre (ng/mL) Standard Deviation 802	—	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 21	2.69 nanograms per millilitre (ng/mL) Standard Deviation NA Standard deviation could not be calculated with data from 1 participant.	297 nanograms per millilitre (ng/mL) Standard Deviation 147	—	—
Serum Concentration of UTTR1147A at Specified Timepoints Day 28	11.3 nanograms per millilitre (ng/mL) Standard Deviation 8.89	173 nanograms per millilitre (ng/mL) Standard Deviation 78.4	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	All Placebo n=96 Participants 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.	MSTT1041A n=23 Participants 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.	UTTR1147A n=119 Participants 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.	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.
Serum Concentration of MSTT1041A at Specified Timepoints Day 2	175 micrograms per millilitre (μg/mL) Standard Deviation 49.1	178 micrograms per millilitre (μg/mL) Standard Deviation 54.3	176 micrograms per millilitre (μg/mL) Standard Deviation 50.0	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 1, 0.5 hours post-dose	206 micrograms per millilitre (μg/mL) Standard Deviation 71.1	227 micrograms per millilitre (μg/mL) Standard Deviation 66.7	210 micrograms per millilitre (μg/mL) Standard Deviation 70.4	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 3	147 micrograms per millilitre (μg/mL) Standard Deviation 40.1	135 micrograms per millilitre (μg/mL) Standard Deviation 41.0	144 micrograms per millilitre (μg/mL) Standard Deviation 40.4	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 7	88.6 micrograms per millilitre (μg/mL) Standard Deviation 32.3	83.9 micrograms per millilitre (μg/mL) Standard Deviation 28.1	87.1 micrograms per millilitre (μg/mL) Standard Deviation 30.9	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 15, pre-dose	32.2 micrograms per millilitre (μg/mL) Standard Deviation 15.2	33.8 micrograms per millilitre (μg/mL) Standard Deviation 17.2	33.5 micrograms per millilitre (μg/mL) Standard Deviation 16.6	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 15, 0.5 hours post-dose	—	144 micrograms per millilitre (μg/mL) Standard Deviation 48.0	—	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 21	—	45.4 micrograms per millilitre (μg/mL) Standard Deviation 20.8	—	—
Serum Concentration of MSTT1041A at Specified Timepoints Day 28	—	22.5 micrograms per millilitre (μg/mL) Standard Deviation 9.17	—	—

Adverse Events

All Placebo

Serious events: 38 serious events

Other events: 29 other events

Deaths: 23 deaths

MSTT1041A

Serious events: 38 serious events

Other events: 42 other events

Deaths: 23 deaths

UTTR1147A

Serious events: 34 serious events

Other events: 40 other events

Deaths: 21 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	All Placebo n=134 participants at risk 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.	MSTT1041A n=130 participants at risk 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.	UTTR1147A n=132 participants at risk 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.
Blood and lymphatic system disorders Anaemia	4.5% 6/134 • Number of events 6 • From Baseline until study completion/discontinuation (up to 60 days)	6.9% 9/130 • Number of events 9 • From Baseline until study completion/discontinuation (up to 60 days)	5.3% 7/132 • Number of events 8 • From Baseline until study completion/discontinuation (up to 60 days)
Gastrointestinal disorders Constipation	4.5% 6/134 • Number of events 6 • From Baseline until study completion/discontinuation (up to 60 days)	7.7% 10/130 • Number of events 10 • From Baseline until study completion/discontinuation (up to 60 days)	7.6% 10/132 • Number of events 10 • From Baseline until study completion/discontinuation (up to 60 days)
Gastrointestinal disorders Nausea	1.5% 2/134 • Number of events 2 • From Baseline until study completion/discontinuation (up to 60 days)	2.3% 3/130 • Number of events 3 • From Baseline until study completion/discontinuation (up to 60 days)	5.3% 7/132 • Number of events 7 • From Baseline until study completion/discontinuation (up to 60 days)
Metabolism and nutrition disorders Hypokalaemia	6.0% 8/134 • Number of events 8 • From Baseline until study completion/discontinuation (up to 60 days)	6.9% 9/130 • Number of events 9 • From Baseline until study completion/discontinuation (up to 60 days)	6.1% 8/132 • Number of events 10 • From Baseline until study completion/discontinuation (up to 60 days)
Nervous system disorders Headache	3.0% 4/134 • Number of events 4 • From Baseline until study completion/discontinuation (up to 60 days)	5.4% 7/130 • Number of events 8 • From Baseline until study completion/discontinuation (up to 60 days)	3.0% 4/132 • Number of events 4 • From Baseline until study completion/discontinuation (up to 60 days)
Psychiatric disorders Anxiety	0.75% 1/134 • Number of events 1 • From Baseline until study completion/discontinuation (up to 60 days)	3.8% 5/130 • Number of events 5 • From Baseline until study completion/discontinuation (up to 60 days)	6.1% 8/132 • Number of events 8 • From Baseline until study completion/discontinuation (up to 60 days)
Skin and subcutaneous tissue disorders Dry skin	3.7% 5/134 • Number of events 5 • From Baseline until study completion/discontinuation (up to 60 days)	3.1% 4/130 • Number of events 4 • From Baseline until study completion/discontinuation (up to 60 days)	6.8% 9/132 • Number of events 9 • From Baseline until study completion/discontinuation (up to 60 days)
Vascular disorders Hypertension	3.0% 4/134 • Number of events 4 • From Baseline until study completion/discontinuation (up to 60 days)	6.2% 8/130 • Number of events 8 • From Baseline until study completion/discontinuation (up to 60 days)	1.5% 2/132 • Number of events 2 • From Baseline until study completion/discontinuation (up to 60 days)
Vascular disorders Hypotension	3.7% 5/134 • Number of events 6 • From Baseline until study completion/discontinuation (up to 60 days)	5.4% 7/130 • Number of events 8 • From Baseline until study completion/discontinuation (up to 60 days)	3.8% 5/132 • Number of events 6 • From Baseline until study completion/discontinuation (up to 60 days)

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER