Trial Outcomes & Findings for Study of Efficacy and Safety of MAS825 in Patients With COVID-19 (NCT NCT04382651)

NCT ID: NCT04382651

Last Updated: 2022-08-10

Results Overview

The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. In practice, it is rare for any participant to accumulate more than 55 points. APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 140 participants
• Primary outcome timeframe: up to Day 15
• Results posted on: 2022-08-10

Participant Flow

Participants took part in 21 investigative sites in 1 country, United States.

The participants were screened within 24 hours prior to enrollment. The single dose was administered within a maximum of 24 hours after screening and baseline assessments.

Participant milestones

Measure	MAS825 + SoC Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC Single dose of matching Placebo by intravenous infusion in addition to SoC
Overall Study STARTED	69	71
Overall Study Safety Analysis Set	68	70
Overall Study Pharmacokinetics (PK) Analysis Set	63	0
Overall Study COMPLETED	38	43
Overall Study NOT COMPLETED	31	28

Reasons for withdrawal

Measure	MAS825 + SoC Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC Single dose of matching Placebo by intravenous infusion in addition to SoC
Overall Study Death	26	23
Overall Study Lost to Follow-up	3	4
Overall Study Withdrawal by Subject	2	0
Overall Study Physician Decision	0	1

Baseline Characteristics

Study of Efficacy and Safety of MAS825 in Patients With COVID-19

Baseline characteristics by cohort

Measure	MAS825 + SoC n=69 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=71 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC	Total n=140 Participants Total of all reporting groups
Age, Continuous	65.3 Years STANDARD_DEVIATION 12.46 • n=93 Participants	63.7 Years STANDARD_DEVIATION 12.91 • n=4 Participants	64.5 Years STANDARD_DEVIATION 12.67 • n=27 Participants
Sex: Female, Male Female	30 Participants n=93 Participants	23 Participants n=4 Participants	53 Participants n=27 Participants
Sex: Female, Male Male	39 Participants n=93 Participants	48 Participants n=4 Participants	87 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants	8 Participants n=4 Participants	14 Participants n=27 Participants
Race (NIH/OMB) White	51 Participants n=93 Participants	52 Participants n=4 Participants	103 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants	7 Participants n=4 Participants	13 Participants n=27 Participants

PRIMARY outcome

Timeframe: up to Day 15

Population: Safety Analysis Set

The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. In practice, it is rare for any participant to accumulate more than 55 points.

APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.

Outcome measures

Measure	MAS825 + SoC n=68 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC
APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)	14.5 Score on a scale Standard Error 1.87	13.5 Score on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15

Population: Safety Analysis Set

C-reactive protein (CRP) is a blood test marker for inflammation in the body. It was analyzed on a log-scale fitting a repeated measures mixed model: treatment, visit, stratification factors, visit * treatment and visit * stratification factors as fixed effects and log-transformed baseline score and visit * log-transformed baseline score as continuous covariate. Values reported were back-transformed to original scale.

Outcome measures

Measure	MAS825 + SoC n=68 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC
Serum C-reactive Protein (CRP) Levels Day 2	55.50 Milligram / Liter Standard Error 1.11	57.70 Milligram / Liter Standard Error 1.10
Serum C-reactive Protein (CRP) Levels Day 4	28.30 Milligram / Liter Standard Error 1.19	37.10 Milligram / Liter Standard Error 1.19
Serum C-reactive Protein (CRP) Levels Day 6	19.80 Milligram / Liter Standard Error 1.24	22.30 Milligram / Liter Standard Error 1.24
Serum C-reactive Protein (CRP) Levels Day 8	15.00 Milligram / Liter Standard Error 1.31	16.6 Milligram / Liter Standard Error 1.30
Serum C-reactive Protein (CRP) Levels Day 10	10.10 Milligram / Liter Standard Error 1.38	19.80 Milligram / Liter Standard Error 1.35
Serum C-reactive Protein (CRP) Levels Day 12	11.00 Milligram / Liter Standard Error 1.42	15.80 Milligram / Liter Standard Error 1.39
Serum C-reactive Protein (CRP) Levels Day 14	7.30 Milligram / Liter Standard Error 1.43	13.20 Milligram / Liter Standard Error 1.39
Serum C-reactive Protein (CRP) Levels Day 15	5.70 Milligram / Liter Standard Error 1.40	11.60 Milligram / Liter Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15

Population: Safety Analysis Set

Ferritin is a blood test marker for inflammation in the body. For a standard ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It was analyzed on a log-scale fitting a repeated measures mixed model: treatment, visit, stratification factors, visit * treatment and visit * stratification factors as fixed effects and log-transformed baseline score and visit * log-transformed baseline score as continuous covariate. Values reported were back-transformed to original scale.

Outcome measures

Measure	MAS825 + SoC n=68 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC
Ferritin Levels Day 2	773.20 Microgram / Liter Standard Error 1.05	800.20 Microgram / Liter Standard Error 1.05
Ferritin Levels Day 4	692.70 Microgram / Liter Standard Error 1.05	701.40 Microgram / Liter Standard Error 1.05
Ferritin Levels Day 6	687.50 Microgram / Liter Standard Error 1.10	622.10 Microgram / Liter Standard Error 1.10
Ferritin Levels Day 8	674.00 Microgram / Liter Standard Error 1.12	667.80 Microgram / Liter Standard Error 1.11
Ferritin Levels Day 10	670.00 Microgram / Liter Standard Error 1.16	776.00 Microgram / Liter Standard Error 1.15
Ferritin Levels Day 12	680.00 Microgram / Liter Standard Error 1.18	754.50 Microgram / Liter Standard Error 1.17
Ferritin Levels Day 14	541.70 Microgram / Liter Standard Error 1.22	595.70 Microgram / Liter Standard Error 1.22
Ferritin Levels Day 15	502.90 Microgram / Liter Standard Error 1.21	504.20 Microgram / Liter Standard Error 1.21

SECONDARY outcome

Timeframe: Until Day 15 (Assessments on Days 2, 4, 6, 8, 10, 12, 14 and 15) and until Day 29 (Additional assessments on Days 17, 19, 21, 23, 25, 27 and 29)

Population: Safety Analysis Set

Number of participants not requiring mechanical ventilation for survival until Day 15 and Day 29: defined by WHO 9-point ordinal scale score of < 6 points at all time points assessments.

The scoring is - Uninfected patients have a score 0. - Ambulatory patients can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support). - Patients who die have a score 8.

Missing data values were handled as follows: For participants who died prior to Day 29, the score for death was imputed for all following visits up to and including Day 29. For all the other participants, last observation carried forward was applied up to and including Day 29.

Outcome measures

Measure	MAS825 + SoC n=68 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC
Number of Participants Not Requiring Mechanical Ventilation for Survival Until Day 15	41 Participants	47 Participants
Number of Participants Not Requiring Mechanical Ventilation for Survival Until Day 29	39 Participants	45 Participants

SECONDARY outcome

Timeframe: Baseline, Day 15 and Day 29

Population: Safety Analysis Set

Number of participants with at least one-point improvement from baseline in clinical status, which was measured with WHO 9-point ordinal scale.

The scoring is - Uninfected patients have a score 0. - Ambulatory patients can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support). - Patients who die have a score 8.

Missing data values were handled as follows: For participants who died prior to Day 29, the score for death was imputed for all following visits up to and including Day 29. For all the other participants, last observation carried forward was applied up to and including Day 29.

Outcome measures

Measure	MAS825 + SoC n=68 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC
Number of Participants With at Least One-point Improvement From Baseline in Clinical Status Day 15	39 Participants	39 Participants
Number of Participants With at Least One-point Improvement From Baseline in Clinical Status Day 29	43 Participants	46 Participants

SECONDARY outcome

Timeframe: Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27, 29, 45 and 127

Population: Safety Analysis Set

Clinical status was measured with World Health Organization (WHO) 9-point ordinal scale.

The scoring is - Uninfected patients have a score 0. - Ambulatory patients can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation). - Patients who die have a score 8.

Missing data values were handled as follows: For participants who died prior to Day 127, the score for death was imputed for all following visits up to and including Day 127. For all the other participants, last observation carried forward was applied up to and including Day 127.

Outcome measures

Measure	MAS825 + SoC n=68 Participants Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 Participants Single dose of matching Placebo by intravenous infusion in addition to SoC
Clinical Status Over Time Baseline	4.8 Score on a scale Standard Deviation 0.38	4.7 Score on a scale Standard Deviation 0.49
Clinical Status Over Time Day 2	4.8 Score on a scale Standard Deviation 0.71	4.7 Score on a scale Standard Deviation 0.57
Clinical Status Over Time Day 4	4.8 Score on a scale Standard Deviation 0.90	4.7 Score on a scale Standard Deviation 1.13
Clinical Status Over Time Day 6	4.8 Score on a scale Standard Deviation 1.27	4.7 Score on a scale Standard Deviation 1.40
Clinical Status Over Time Day 8	4.9 Score on a scale Standard Deviation 1.63	4.5 Score on a scale Standard Deviation 1.64
Clinical Status Over Time Day 10	4.9 Score on a scale Standard Deviation 1.76	4.6 Score on a scale Standard Deviation 1.80
Clinical Status Over Time Day 12	5.0 Score on a scale Standard Deviation 1.97	4.7 Score on a scale Standard Deviation 2.04
Clinical Status Over Time Day 14	5.0 Score on a scale Standard Deviation 2.04	4.8 Score on a scale Standard Deviation 2.09
Clinical Status Over Time Day 15	4.5 Score on a scale Standard Deviation 2.59	4.2 Score on a scale Standard Deviation 2.58
Clinical Status Over Time Day 17	4.4 Score on a scale Standard Deviation 2.64	4.2 Score on a scale Standard Deviation 2.67
Clinical Status Over Time Day 19	4.4 Score on a scale Standard Deviation 2.73	4.1 Score on a scale Standard Deviation 2.70
Clinical Status Over Time Day 21	4.4 Score on a scale Standard Deviation 2.78	4.1 Score on a scale Standard Deviation 2.71
Clinical Status Over Time Day 23	4.4 Score on a scale Standard Deviation 2.78	4.1 Score on a scale Standard Deviation 2.73
Clinical Status Over Time Day 25	4.4 Score on a scale Standard Deviation 2.79	4.2 Score on a scale Standard Deviation 2.76
Clinical Status Over Time Day 27	4.4 Score on a scale Standard Deviation 2.81	4.2 Score on a scale Standard Deviation 2.76
Clinical Status Over Time Day 29	4.2 Score on a scale Standard Deviation 2.99	3.8 Score on a scale Standard Deviation 3.00
Clinical Status Over Time Day 45	4.0 Score on a scale Standard Deviation 3.19	3.7 Score on a scale Standard Deviation 3.24
Clinical Status Over Time Day 127	3.8 Score on a scale Standard Deviation 3.48	3.3 Score on a scale Standard Deviation 3.41

Adverse Events

MAS825 + SoC

Serious events: 31 serious events

Other events: 20 other events

Deaths: 26 deaths

Placebo + SoC

Serious events: 28 serious events

Other events: 19 other events

Deaths: 23 deaths

Total

Serious events: 59 serious events

Other events: 39 other events

Deaths: 49 deaths

Serious adverse events

Measure	MAS825 + SoC n=68 participants at risk Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 participants at risk Single dose of matching Placebo by intravenous infusion in addition to SoC	Total n=138 participants at risk Total
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Blood and lymphatic system disorders Pancytopenia	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Acute coronary syndrome	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.9% 2/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Bradycardia	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Cardiac arrest	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	4.3% 3/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	3.6% 5/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Cardiac failure acute	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.9% 2/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Cardiogenic shock	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Cardiac disorders Myocarditis	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
General disorders Hypothermia	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
General disorders Multiple organ dysfunction syndrome	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.2% 3/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Immune system disorders Haemophagocytic lymphohistiocytosis	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations COVID-19	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations COVID-19 pneumonia	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.7% 4/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	4.3% 6/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Fungaemia	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Pneumonia	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Pneumonia klebsiella	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Sepsis	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.2% 3/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Septic shock	4.4% 3/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.2% 3/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Investigations Alanine aminotransferase increased	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Investigations Aspartate aminotransferase increased	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Investigations Electrocardiogram QT prolonged	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Metabolism and nutrition disorders Metabolic acidosis	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Nervous system disorders Cerebrovascular accident	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.9% 2/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.2% 3/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Nervous system disorders Metabolic encephalopathy	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Renal and urinary disorders Acute kidney injury	4.4% 3/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.7% 4/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.1% 7/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Renal and urinary disorders Nephropathy	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Renal and urinary disorders Renal failure	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	8.8% 6/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	4.3% 6/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	16.2% 11/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	11.4% 8/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	13.8% 19/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.4% 5/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	4.3% 6/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	7.4% 5/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	7.1% 5/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	7.2% 10/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Vascular disorders Distributive shock	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.00% 0/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Vascular disorders Hypertension	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	0.72% 1/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Vascular disorders Hypotension	1.5% 1/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 1/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Vascular disorders Shock haemorrhagic	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.9% 2/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	1.4% 2/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.

Other adverse events

Measure	MAS825 + SoC n=68 participants at risk Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC	Placebo + SoC n=70 participants at risk Single dose of matching Placebo by intravenous infusion in addition to SoC	Total n=138 participants at risk Total
Cardiac disorders Atrial fibrillation	5.9% 4/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.7% 4/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.8% 8/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Pneumonia bacterial	8.8% 6/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	2.9% 2/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.8% 8/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Infections and infestations Urinary tract infection	2.9% 2/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	7.1% 5/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.1% 7/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Investigations Transaminases increased	0.00% 0/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	7.1% 5/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	3.6% 5/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Psychiatric disorders Anxiety	4.4% 3/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	8.6% 6/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	6.5% 9/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Renal and urinary disorders Acute kidney injury	13.2% 9/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	7.1% 5/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	10.1% 14/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.
Vascular disorders Hypotension	7.4% 5/68 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	4.3% 3/70 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.	5.8% 8/138 • Adverse events were reported from the date of administration of study treatment to day 127. Any sign or symptom that occurs during the study treatment plus the 127 days post treatment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER