Trial Outcomes & Findings for Zilucoplan® in Improving Oxygenation, Short-, Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure (NCT NCT04382755)

NCT ID: NCT04382755

Last Updated: 2023-09-14

Results Overview

defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

81 participants

Primary outcome timeframe

at predose, day 6 and day 15 (or at discharge, whichever comes first)

Results posted on

2023-09-14

Participant Flow

81 patients were randomized at the 9 participating centers.

Participant milestones

Participant milestones
Measure	Group A (Active) Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® 32.4mg once daily on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Overall Study STARTED	55	26
Overall Study Treated	54	24
Overall Study COMPLETED	54	24
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A (Active) Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® 32.4mg once daily on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Overall Study Withdrawal by Subject	1	0
Overall Study did not receive allocated intervention due to clinical error	0	1
Overall Study did not meet inclusion criteria but was randomized without receiving the allocated intervention	0	1

Baseline Characteristics

For 4 participants, not all information was present to calculate the SOFA score at baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)	Total n=78 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=54 Participants	0 Participants n=24 Participants	0 Participants n=78 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=54 Participants	12 Participants n=24 Participants	41 Participants n=78 Participants
Age, Categorical >=65 years	25 Participants n=54 Participants	12 Participants n=24 Participants	37 Participants n=78 Participants
Age, Continuous	62 years n=54 Participants	64.8 years n=24 Participants	63 years n=78 Participants
Sex: Female, Male Female	5 Participants n=54 Participants	5 Participants n=24 Participants	10 Participants n=78 Participants
Sex: Female, Male Male	49 Participants n=54 Participants	19 Participants n=24 Participants	68 Participants n=78 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=54 Participants	0 Participants n=24 Participants	0 Participants n=78 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=54 Participants	23 Participants n=24 Participants	77 Participants n=78 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=54 Participants	1 Participants n=24 Participants	1 Participants n=78 Participants
Ordinal scale for clinical improvement 2. on invasive mechanical ventilation of ECMO	8 Participants n=54 Participants	2 Participants n=24 Participants	10 Participants n=78 Participants
Ordinal scale for clinical improvement 3. on non-invasive ventilation of high flow oxygen devices	19 Participants n=54 Participants	8 Participants n=24 Participants	27 Participants n=78 Participants
Ordinal scale for clinical improvement 4. hospitalized, requiring supplemental oxygen	26 Participants n=54 Participants	14 Participants n=24 Participants	40 Participants n=78 Participants
Ordinal scale for clinical improvement 5. hospitalized, not requiring supplemental oxygen	1 Participants n=54 Participants	0 Participants n=24 Participants	1 Participants n=78 Participants
Ethnicity African	4 Participants n=54 Participants	0 Participants n=24 Participants	4 Participants n=78 Participants
Ethnicity Arabian	3 Participants n=54 Participants	1 Participants n=24 Participants	4 Participants n=78 Participants
Ethnicity Asian	1 Participants n=54 Participants	0 Participants n=24 Participants	1 Participants n=78 Participants
Ethnicity Caucasian	46 Participants n=54 Participants	22 Participants n=24 Participants	68 Participants n=78 Participants
Ethnicity Other	0 Participants n=54 Participants	1 Participants n=24 Participants	1 Participants n=78 Participants
Sequential Organ Failure Assessment (SOFA score) score 1-2	29 Participants n=51 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	14 Participants n=23 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	43 Participants n=74 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.
Sequential Organ Failure Assessment (SOFA score) score 3-4	14 Participants n=51 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	7 Participants n=23 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	21 Participants n=74 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.
Sequential Organ Failure Assessment (SOFA score) score 5-6	1 Participants n=51 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	2 Participants n=23 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	3 Participants n=74 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.
Sequential Organ Failure Assessment (SOFA score) score 7-8	7 Participants n=51 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	0 Participants n=23 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.	7 Participants n=74 Participants • For 4 participants, not all information was present to calculate the SOFA score at baseline.
Arterial hypertension yes	26 Participants n=54 Participants	10 Participants n=24 Participants	36 Participants n=78 Participants
Arterial hypertension no	28 Participants n=54 Participants	14 Participants n=24 Participants	42 Participants n=78 Participants
Diabetes mellitus yes	26 Participants n=54 Participants	10 Participants n=24 Participants	36 Participants n=78 Participants
Diabetes mellitus no	28 Participants n=54 Participants	14 Participants n=24 Participants	42 Participants n=78 Participants
Cardiovascular disease yes	9 Participants n=54 Participants	10 Participants n=24 Participants	19 Participants n=78 Participants
Cardiovascular disease no	45 Participants n=54 Participants	14 Participants n=24 Participants	59 Participants n=78 Participants
Chronic kidney disease yes	4 Participants n=54 Participants	0 Participants n=24 Participants	4 Participants n=78 Participants
Chronic kidney disease no	50 Participants n=54 Participants	24 Participants n=24 Participants	74 Participants n=78 Participants
Glucocorticoids at randomisation yes	49 Participants n=54 Participants	18 Participants n=24 Participants	67 Participants n=78 Participants
Glucocorticoids at randomisation no	5 Participants n=54 Participants	6 Participants n=24 Participants	11 Participants n=78 Participants
glucocorticoid use during first 28 days yes	52 Participants n=54 Participants	21 Participants n=24 Participants	73 Participants n=78 Participants
glucocorticoid use during first 28 days no	2 Participants n=54 Participants	3 Participants n=24 Participants	5 Participants n=78 Participants
Anticoagulants at randomisation yes	49 Participants n=54 Participants	21 Participants n=24 Participants	70 Participants n=78 Participants
Anticoagulants at randomisation no	5 Participants n=54 Participants	3 Participants n=24 Participants	8 Participants n=78 Participants
Antibiotics at randomisation yes	16 Participants n=54 Participants	2 Participants n=24 Participants	18 Participants n=78 Participants
Antibiotics at randomisation no	38 Participants n=54 Participants	22 Participants n=24 Participants	60 Participants n=78 Participants
Remdesivir at randomisation yes	7 Participants n=54 Participants	2 Participants n=24 Participants	9 Participants n=78 Participants
Remdesivir at randomisation no	47 Participants n=54 Participants	22 Participants n=24 Participants	69 Participants n=78 Participants
PaO2/FiO2 ratio at baseline	169.2 mmHG STANDARD_DEVIATION 93.8 • n=54 Participants	175.1 mmHG STANDARD_DEVIATION 92.5 • n=24 Participants	171.1 mmHG STANDARD_DEVIATION 92.8 • n=78 Participants
A-a gradient at baseline	271.8 mmHg STANDARD_DEVIATION 211.1 • n=54 Participants	237.2 mmHg STANDARD_DEVIATION 207.8 • n=24 Participants	260.6 mmHg STANDARD_DEVIATION 209.2 • n=78 Participants
Days of hospitalization at randomisation	3 days n=54 Participants	2 days n=24 Participants	2 days n=78 Participants
Days of symptoms at randomisation	10 days n=54 Participants	10 days n=24 Participants	10 days n=78 Participants
Admitted to ICU at randomisation	30 Participants n=54 Participants	12 Participants n=24 Participants	42 Participants n=78 Participants

PRIMARY outcome

Timeframe: at predose, day 6 and day 15 (or at discharge, whichever comes first)

defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

Outcome measures

Outcome measures
Measure	Group A (Active) n=52 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=20 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Change in Oxygenation change from baseline in PaO2/FiO2 day 6	56.4 mmHg Interval 31.9 to 80.9	20.6 mmHg Interval 17.3 to 58.5
Change in Oxygenation change from baseline in PaO2/FiO2 day 15	123.5 mmHg Interval 94.3 to 152.7	83.7 mmHg Interval 39.0 to 128.4
Change in Oxygenation change from baseline in a/A PO2 day 6	0.10 mmHg Interval 0.06 to 0.15	0.04 mmHg Interval 0.04 to 0.11
Change in Oxygenation change from baseline in a/A PO2 day 15	0.25 mmHg Interval 0.19 to 0.31	0.17 mmHg Interval 0.08 to 0.26

PRIMARY outcome

Timeframe: at predose, day 6 and day 15 (or at discharge, whichever comes first)

defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

Outcome measures

Outcome measures
Measure	Group A (Active) n=52 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=20 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Change in Oxygenation (A-a) gradient day 15	58.6 mmHg Interval 44.9 to 76.5	86.9 mmHg Interval 57.9 to 130.6
Change in Oxygenation (A-a) gradient day 6	114.6 mmHg Interval 92.6 to 141.9	146.7 mmHg Interval 105.4 to 204.3

SECONDARY outcome

Timeframe: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).

6-point ordinal scale defined as 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO; 3. Hospitalized, on non-invasive ventilation 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen 6. Not hospitalized

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement mean change in 6-point ordinal scale change day 6	0.1 score on a scale Standard Deviation 1.0	0.1 score on a scale Standard Deviation 0.9
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement mean change in 6-point ordinal scale change day 15	1.2 score on a scale Standard Deviation 1.4	1 score on a scale Standard Deviation 1.5
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement mean change in 6-point ordinal scale change day 28	1.7 score on a scale Standard Deviation 1.5	1.3 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

defined as SpO2 \< 93% breathing room air or the dependence on supplemental oxygen

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Days With Hypoxia	13 days Interval 3.0 to 28.0	10 days Interval 2.0 to 28.0

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Days of Supplemental Oxygen Use	13 days Interval 3.0 to 28.0	10 days Interval 2.0 to 28.0

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Time to Absence of Fever (Defined as 37.1°C or More) for More Than 48h Without Antipyretic	7 days Interval 1.0 to 28.0	3 days Interval 1.0 to 28.0

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

defined as 37.1°C or more

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Days With Fever	7 days Interval 0.0 to 28.0	4 days Interval 0.0 to 20.0

SECONDARY outcome

Timeframe: day 1, day 6

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Mean Change in CRP Levels Between Day 1 and Day 6	-89.6 mg/mL Standard Deviation 91.5	-100 mg/mL Standard Deviation 61.9

SECONDARY outcome

Timeframe: day 1, day 15

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Mean Change in CRP Levels Between Day 1 and Day 15 (or Discharge Whichever Comes First)	-91.0 mg/mL Standard Deviation 106.3	-96.2 mg/mL Standard Deviation 98.4

SECONDARY outcome

Timeframe: day 1, day 6

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Mean Change in Ferritin Levels Between Day 1 and Day 6	-544.4 µg/L Standard Deviation 1489.9	-282.3 µg/L Standard Deviation 517.0

SECONDARY outcome

Timeframe: day 1, day 15

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Mean Change in Ferritin Levels Between Day 1 and Day 15 (or Discharge, Whichever Comes First)	-201.0 µg/L Standard Deviation 6204.5	-303.9 µg/L Standard Deviation 948.4

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

Any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With Adverse Events	39 Participants	17 Participants

SECONDARY outcome

Timeframe: at 10-20 weeks follow-up

A serious adverse event is any untoward medical occurrence that: * results in death * is life-threatening * requires inpatient hospitalisation or prolongation of existing hospitalisation * results in persistent or significant disability/incapacity * consists of a congenital anomaly or birth defect Other 'important medical events' may also be considered serious if they jeopardise the subject or require an intervention to prevent one of the above consequences. NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With Serious Adverse Events	10 Participants	5 Participants

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

A serious adverse reaction, the nature and severity of which is not consistent with the information about the medicinal product in question set out: * in the case of a product with a marketing authorisation, in the summary of product characteristics (SmPC) for that product * in the case of any other investigational medicinal product, in the investigator's brochure (IB) relating to the study in question

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With SUSAR's (Suspected Unexpected Serious Adverse Reaction)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

An adverse event that is both serious and, in the opinion of the reporting Investigator, believed with reasonable probability to be due to one of the study treatments, based on the information provided.

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With SAR's (Serious Adverse Reaction)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: at 12-22 weeks follow-up

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Duration of Hospital Stay	15 days Interval 5.0 to 74.0	13 days Interval 3.0 to 43.0

SECONDARY outcome

Timeframe: at 12-22 weeks follow-up

Outcome measures

Outcome measures
Measure	Group A (Active) n=47 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=19 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Duration of Hospital Stay in Survivors	15 days Interval 5.0 to 74.0	12 days Interval 3.0 to 43.0

SECONDARY outcome

Timeframe: day 1, day 6 or on discharge, whichever is first

Population: Change of SOFA score between day 1 and day 6

The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Score ranges from 0 (best) to 24 (worst) points.

Outcome measures

Outcome measures
Measure	Group A (Active) n=43 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=21 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 6 (or on Discharge, Whichever is First) improvement or discharge	21 Participants	10 Participants
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 6 (or on Discharge, Whichever is First) no change	11 Participants	6 Participants
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 6 (or on Discharge, Whichever is First) death or deterioration	11 Participants	5 Participants

SECONDARY outcome

Timeframe: day 1, day 15 or on discharge, whichever is first

Population: Change of SOFA score between day 1 and day 15

Outcome measures

Outcome measures
Measure	Group A (Active) n=43 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=17 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 15 (or on Discharge, Whichever is First) improvement or discharge	33 Participants	12 Participants
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 15 (or on Discharge, Whichever is First) no change	5 Participants	1 Participants
Number of Participants With Improvement, No Change, Death or Deterioration in SOFA Score Between Day 1 and Day 15 (or on Discharge, Whichever is First) death or deterioration	5 Participants	4 Participants

SECONDARY outcome

Timeframe: day 28

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With Nosocomial Bacterial or Invasive Fungal Infection for 28 Days (Phone Call) After Enrollment in Trial	12 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 28

The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Median Time to at Least a 2-point Improvement on the 6-point Ordinal Scale or Discharge During the 28-day Assessment Period (Range) - Days	15 days Interval 2.0 to 28.0	12 days Interval 6.0 to 28.0

SECONDARY outcome

Timeframe: at 12-22 weeks follow-up

Outcome measures

Outcome measures
Measure	Group A (Active) n=44 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=19 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement category 3	0 Participants	0 Participants
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement category 2	0 Participants	0 Participants
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement category 4	1 Participants	0 Participants
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement category 5	0 Participants	0 Participants
Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement category 6	43 Participants	19 Participants

SECONDARY outcome

Timeframe: during hospital admission (up to 28 days)

Population: For 1 participant of group A and 1 participant of group B, the WHO performance scale was not recorded.

The WHO performance status classification categorises patients as: 0: able to carry out all normal activity without restriction 1. restricted in strenuous activity but ambulatory and able to carry out light work 2. ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours 3. symptomatic and in a chair or in bed for greater than 50% of the day but not bedridden 4. completely disabled; cannot carry out any self-care; totally confined to bed or chair.

Outcome measures

Outcome measures
Measure	Group A (Active) n=43 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=18 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants in Each Category of the WHO Performance Scale category 0	23 Participants	10 Participants
Number of Participants in Each Category of the WHO Performance Scale category 1	18 Participants	7 Participants
Number of Participants in Each Category of the WHO Performance Scale category >=2	2 Participants	1 Participants

SECONDARY outcome

Timeframe: at 12-22 weeks follow-up

Distance in 6 minute walk test. The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Total distance in meters. A higher score has a better outcome

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Result of 6 Minute Walk Test	539.7 meters Standard Deviation 107.7	490.6 meters Standard Deviation 0.18

SECONDARY outcome

Timeframe: at day 28

Population: Population excluding patients that required invasive mechanical ventilation or ECMO within 24 hours prior to or after randomization.

Outcome measures

Outcome measures
Measure	Group A (Active) n=45 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=22 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
All-cause Mortality Rate (Excluding Group That Entered During Ventilation)	3 Participants	5 Participants

SECONDARY outcome

Timeframe: at day 28

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
All-cause Mortality Rate (Including Group That Entered During Ventilation)	5 Participants	5 Participants

SECONDARY outcome

Timeframe: at follow up 12-22 weeks

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
All Cause Mortality for the Entire Study Population	7 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: day 1, day 28 or discharge whichever comes first

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Ventilator-free Days	7 days Interval 0.0 to 27.0	9 days Interval 0.0 to 28.0

OTHER_PRE_SPECIFIED outcome

Timeframe: during hospital admission (up to 28 days)

criteria-defined ARDS criteria-defined ARDS according to the adapted Berlin criteria as follow: * within 1 week of a known Clinical insult or new or worsening respiratory symptoms * bilateral infiltrates not supposed to be of cardiac origin or fluid overload * PaO2/FiO2 \< 300 mmHg

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Time Since Randomization to Progression to ARDS (Acute Respiratory Distress Syndrome)	1 days Interval 1.0 to 14.0	3 days Interval 1.0 to 10.0

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12-22 weeks follow-up

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Number of Participants With Lung Fibrosis on Chest CT Scan at Follow up	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: during hospital admission (up to 28 days)

defined as independence from supplemental oxygen

Outcome measures

Outcome measures
Measure	Group A (Active) n=54 Participants Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 Participants Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Time Since Randomization Until Improvement in Oxygenation	13 days Interval 3.0 to 28.0	10 days Interval 2.0 to 28.0

Adverse Events

Group A (Active)

Serious events: 10 serious events

Other events: 39 other events

Deaths: 7 deaths

Group B (Control)

Serious events: 5 serious events

Other events: 17 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Group A (Active) n=54 participants at risk Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 participants at risk Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Vascular disorders hypertension	14.8% 8/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	8.3% 2/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Investigations alanine animontransferase increased	7.4% 4/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Investigations aspartate animontransferase increased	5.6% 3/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.7% 2/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	12.5% 3/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Respiratory, thoracic and mediastinal disorders pneumonia pseudomonal	0.00% 0/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	8.3% 2/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Blood and lymphatic system disorders anemia	7.4% 4/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	8.3% 2/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Psychiatric disorders anxiety	11.1% 6/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Psychiatric disorders delirium	5.6% 3/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Psychiatric disorders insomnia	9.3% 5/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Gastrointestinal disorders constipation	13.0% 7/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	20.8% 5/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Metabolism and nutrition disorders decreased appetite	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	8.3% 2/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Metabolism and nutrition disorders hyperglycemia	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	12.5% 3/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Metabolism and nutrition disorders hypoalbuminia	5.6% 3/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations pneumonia	9.3% 5/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.

Additional Information

Anja Delporte

UZ Gent

Phone: +3293320228

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Group A (Active) n=54 participants at risk Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan® Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group B (Control) n=24 participants at risk Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first) Placebo: standard of care treatment + 1 week of prophylactic antibiotics + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)
Cardiac disorders Cardiac arrest	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.00% 0/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Respiratory, thoracic and mediastinal disorders hypoxia	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.7% 2/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	12.5% 3/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Immune system disorders Aspergillus infection	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Nervous system disorders hypoxic-sichaemic encephalopathy	0.00% 0/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
General disorders death	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
General disorders multiple organ dysfunction syndrome	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Renal and urinary disorders acute kidney injury	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Product Issues thrombosis in device	0.00% 0/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	4.2% 1/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations bronchopulmonary aspergillus	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations Respiratory tract infection bacterial	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations covid-19	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations cytomegalovirus infection	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations enterococcal sepsis	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations pneumonia	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations sepsis	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.
Infections and infestations septic shock	1.9% 1/54 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.	0.00% 0/24 • All-cause mortality monitored for up to 22 weeks, serious adverse events monitored for up to 20 weeks and other adverse events monitored for up to 28 days. Some patients encountered several (serious) adverse events. Therefore, the total count of (serious) adverse events can be higher than the number of affected participants.