Zilucoplan® in Improving Oxygenation, Short-, Longterm Ou... | NCT04382755

Status Module

Name	Class
UCB Pharma	INDUSTRY

Description Module

Detailed Description

This investigator-initiated trial is a phase 2 academic, prospective, 2:1 randomized, open-label, multicenter interventional study designed to investigate the efficacy of subcutaneous Zilucoplan® in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. The hypothesis of the proposed intervention is that Zilucoplan® has profound effects on inhibiting acute lung injury induced by COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury.

We will randomize patients with confirmed COVID19 with acute hypoxic respiratory failure (O2 saturation below 93% on minimal 2l/min O2 therapy; and/or PaO2/FiO2 below 350 mmHg) to receive up to 14 days of SC Zilucoplan® on top of standard of care (active group A), or to receive standard of care treatment (control group B). Randomization will be done at a 2:1 ratio active: control group. In the active group A, patients will additionally receive daily antibiotics (daily 3rd generation cephalosporin IV while in hospital, followed by oral ciprofloxacin while discharged) as primary prophylaxis against meningococcal disease until 14 days after the last dose of Zilucoplan®. Control group B will receive standard of care and prophylactic antibiotics (3rd generation cephalosporin IV) for only 1 week (or until hospital discharge whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. In case of allergies to these antibiotics, or on clinical indication, these antibiotics may be switched to antibiotics that also cover Neisseria meningitidis.

To measure the effectiveness of Zilucoplan® on restoring lung homeostasis, the primary endpoint of this intervention is measuring change in oxygenation parameters comparing baseline values (pretreatment) to values predose day 6 and to values at day 15 (or discharge whichever comes first) post-randomizationin group A and group B and the differences in these values between group A and group B.

Label	Type	Description	Intervention Names
Group A (active)	Active Comparator	Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan®	Drug: Zilucoplan®
Group B (control)	Placebo Comparator	Standard of Care (SoC) + 1 week of prophylactic antibiotics (or until hospital discharge, whichever comes first)	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Zilucoplan®	Drug	14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®	Group A (active)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Oxygenation	defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio	at predose, day 6 and day 15 (or at discharge, whichever comes first)

Secondary Outcomes

Measure	Description	Time Frame
Mean Change in 6-point Ordinal Scale Change for Clinical Improvement	6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized	between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).

Other Outcomes

Measure	Description	Time Frame
Number of Ventilator-free Days		day 1, day 28 or discharge whichever comes first
Time Since Randomization to Progression to ARDS (Acute Respiratory Distress Syndrome)	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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Recent (≥6 days and ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period. For patients with a negative SARS-CoV-2 PCR and either a positive SARS-CoV-2 antigen or antibody test, the presence of suggestive lesions for COVID-19 on chest-CT scan is mandatory.
In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable SARS-CoV-2-infected. In all cases, this needs confirmation by later seroconversion.
Presence of hypoxia defined as :
- O2 saturation below 93% on minimal 2l/min O2 therapy; and/or
- PaO2/FiO2 below 350 mmHg (Strongly recommended: patient in upright position, after minimal 3 minutes without supplemental oxygen; In ventilated patients or ECMO patients PaO2 can be taken from invasive arterial line and FiO2 taken directly from mechanical ventilation settings).
Signs of acute lung injury and/or cytokine release syndrome defined as ANY of the following
- serum ferritin concentration >1000 mcg/L and rising since last 24h
- single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device (Optiflow) or non-invasive or invasive mechanical ventilation
- lymphopenia defined as <800 lymphocytes/microliter and two of the following extra criteria
  - Ferritin > 700 mcg/L and rising since last 24h
  - Increased LDH (above 300 IU/L) and rising since last 24h
  - D-Dimers > 1000 ng/mL and rising since last 24h
  - CRP above 70 mg/L and rising since last 24h and absence of bacterial infection
  - if three of the above are present at admission, no need to document 24h rise
Low dose Chest CT or HRCT or Angio Chest CT scan showing bilateral infiltrates within last 2 days prior to randomisation
Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients
Age ≥ 18 years
Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Women of childbearing potential must consistently and correctly use (during the entire treatment period and 4weeks after last Zilucoplan® administration ) at least 1 highly effective method for contraception.
Willing and able to provide informed consent or legal representative willing to provide informed consent

Exclusion Criteria:

Patients with known history of serious allergic reactions, including anaphylaxis, to Zilucoplan® or inability to receive antibiotic prophylaxis due to allergy to ALL of the antibiotics that can be given for prophylaxis of meningococcal disease
History of active or past meningococcal disease
Invasive mechanical ventilation > 24 h at randomization
Patient on ECMO at screening
Clinical frailty scale above 3 before onset of the COVID-19 episode
Weight below 54 kg as measured max 1 week prior to inclusion
Weight above 150 kg as measured max 1 week prior to inclusion
Active bacterial or fungal infection
Unlikely to survive beyond 48h
Neutrophil count below 1500 cells/microliter
Platelets below 50.000/microliter
Patients enrolled in another investigational drug study
Patients on high dose systemic steroids (> 8 mg methylprednisolone or equivalent for more than 1 month) or other moderately immunosuppressive drugs (in the opinion of the investigator) for COVID19 unrelated disorder
Patients on current complement inhibiting drugs
Serum transaminase levels >5 times upper limit of normal, unless there are clear signs of cytokine release syndrome defined by LDH >300 IU/L and ferritin >700 ng/ml
Pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening)

Name	Affiliation	Role
Bart N Lambrecht, MDPhD	University Ghent	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
OLVZ Aalst		Aalst		9300	Belgium
AZ Sint Jan Brugge

PubMed Identifier	Type	Citation	Retractions
35945604	Derived	De Leeuw E, Van Damme KFA, Declercq J, Bosteels C, Maes B, Tavernier SJ, Detalle L, Smart T, Glatt S, Debeuf N, Deckers J, Lameire S, Vandecasteele SJ, De Neve N, Demedts IK, Govaerts E, Knoop C, Vanhove K, Moutschen M, Terryn W, Depuydt P, Van Braeckel E, Haerynck F, Hendrickx TCJ, Parrein V, Lalla M, Brittain C, Lambrecht BN. Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial. Respir Res. 2022 Aug 9;23(1):202. doi: 10.1186/s12931-022-02126-2.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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®
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 9, 2021	Jul 4, 2022

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

change from baseline in PaO2/FiO2 day 6

Title	Measurements
	OG00056.4(31.9 to 80.9) OG00120.6(17.3 to 58.5)

change from baseline in PaO2/FiO2 day 15

Title	Measurements
	OG000

Primary

Change in Oxygenation

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

Posted

Geometric Least Squares Mean

95% Confidence Interval

mmHg

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

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Mean Change in 6-point Ordinal Scale Change for Clinical Improvement

6-point ordinal scale defined as

Death
Hospitalized, on invasive mechanical ventilation or ECMO;
Hospitalized, on non-invasive ventilation
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen
Not hospitalized

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants

Secondary

Number of Days With Hypoxia

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

Posted

Median

Full Range

days

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Number of Days of Supplemental Oxygen Use

Posted

Median

Full Range

days

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Time to Absence of Fever (Defined as 37.1°C or More) for More Than 48h Without Antipyretic

Posted

Median

Full Range

days

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Number of Days With Fever

defined as 37.1°C or more

Posted

Median

Full Range

days

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Mean Change in CRP Levels Between Day 1 and Day 6

Posted

Mean

Standard Deviation

mg/mL

day 1, day 6

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Mean Change in CRP Levels Between Day 1 and Day 15 (or Discharge Whichever Comes First)

Posted

Mean

Standard Deviation

mg/mL

day 1, day 15

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Mean Change in Ferritin Levels Between Day 1 and Day 6

Posted

Mean

Standard Deviation

µg/L

day 1, day 6

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Mean Change in Ferritin Levels Between Day 1 and Day 15 (or Discharge, Whichever Comes First)

Posted

Mean

Standard Deviation

µg/L

day 1, day 15

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Events

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.

Posted

Count of Participants

Participants

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts

Secondary

Number of Participants With Serious Adverse Events

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.

Posted

Count of Participants

Participants

at 10-20 weeks follow-up

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Secondary

Number of Participants With SUSAR's (Suspected Unexpected Serious Adverse Reaction)

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

Posted

Count of Participants

Participants

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts

Secondary

Number of Participants With SAR's (Serious Adverse Reaction)

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.

Posted

Count of Participants

Participants

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Duration of Hospital Stay

Posted

Median

Full Range

days

at 12-22 weeks follow-up

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

Duration of Hospital Stay in Survivors

Posted

Median

Full Range

days

at 12-22 weeks follow-up

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

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)

Change of SOFA score between day 1 and day 6

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts

Secondary

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)

Change of SOFA score between day 1 and day 15

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts

Secondary

Number of Participants With Nosocomial Bacterial or Invasive Fungal Infection for 28 Days (Phone Call) After Enrollment in Trial

Posted

Count of Participants

Participants

day 28

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

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

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

Posted

Median

Full Range

days

Day 28

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants

Secondary

Number of Participants in Each Category of the 6- Point Ordinal Scale for Clinical Improvement

Posted

Count of Participants

Participants

at 12-22 weeks follow-up

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants

Secondary

Number of Participants in Each Category of the WHO Performance Scale

The WHO performance status classification categorises patients as:

0: able to carry out all normal activity without restriction

restricted in strenuous activity but ambulatory and able to carry out light work
ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
symptomatic and in a chair or in bed for greater than 50% of the day but not bedridden
completely disabled; cannot carry out any self-care; totally confined to bed or chair.

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

Posted

Count of Participants

Participants

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Secondary

Result of 6 Minute Walk Test

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

Posted

Mean

Standard Deviation

meters

at 12-22 weeks follow-up

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants

Secondary

All-cause Mortality Rate (Excluding Group That Entered During Ventilation)

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

Posted

Count of Participants

Participants

at day 28

ID	Title	Description
OG000	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

All-cause Mortality Rate (Including Group That Entered During Ventilation)

Posted

Count of Participants

Participants

at day 28

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Secondary

All Cause Mortality for the Entire Study Population

Posted

Count of Participants

Participants

at follow up 12-22 weeks

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Other Pre-specified

Number of Ventilator-free Days

Posted

Median

Full Range

days

day 1, day 28 or discharge whichever comes first

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Other Pre-specified

Time Since Randomization to Progression to ARDS (Acute Respiratory Distress Syndrome)

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

Posted

Median

Full Range

days

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants

Other Pre-specified

Number of Participants With Lung Fibrosis on Chest CT Scan at Follow up

Posted

Count of Participants

Participants

at 12-22 weeks follow-up

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Other Pre-specified

Time Since Randomization Until Improvement in Oxygenation

defined as independence from supplemental oxygen

Posted

Median

Full Range

days

during hospital admission (up to 28 days)

ID	Title	Description
OG000	Group A (Active)	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®
OG001	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)

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected54 at risk EG0011 affected24 at risk
hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected54 at risk EG0013 affected24 at risk
Aspergillus infection	Immune system disorders	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
hypoxic-sichaemic encephalopathy	Nervous system disorders	Systematic Assessment	EG0000 affected54 at risk EG0011 affected24 at risk
death	General disorders	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
multiple organ dysfunction syndrome	General disorders	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0001 affected54 at risk EG0011 affected24 at risk
thrombosis in device	Product Issues	Systematic Assessment	EG0000 affected54 at risk EG0011 affected24 at risk
bronchopulmonary aspergillus	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
Respiratory tract infection bacterial	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
covid-19	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
cytomegalovirus infection	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
enterococcal sepsis	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
pneumonia	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
sepsis	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk
septic shock	Infections and infestations	Systematic Assessment	EG0001 affected54 at risk EG0010 affected24 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
hypertension	Vascular disorders	Systematic Assessment	EG0008 affected54 at risk EG0012 affected24 at risk
alanine animontransferase increased	Investigations	Systematic Assessment	EG0004 affected54 at risk EG0011 affected24 at risk
aspartate animontransferase increased	Investigations	Systematic Assessment	EG0003 affected54 at risk EG0011 affected24 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected54 at risk EG0013 affected24 at risk
pneumonia pseudomonal	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected54 at risk EG0012 affected24 at risk
anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 affected54 at risk EG0012 affected24 at risk
anxiety	Psychiatric disorders	Systematic Assessment	EG0006 affected54 at risk EG0011 affected24 at risk
delirium	Psychiatric disorders	Systematic Assessment	EG0003 affected54 at risk EG0011 affected24 at risk
insomnia	Psychiatric disorders	Systematic Assessment	EG0005 affected54 at risk EG0010 affected24 at risk
constipation	Gastrointestinal disorders	Systematic Assessment	EG0007 affected54 at risk EG0015 affected24 at risk
decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected54 at risk EG0012 affected24 at risk
hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected54 at risk EG0013 affected24 at risk
hypoalbuminia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 affected54 at risk EG0010 affected24 at risk
pneumonia	Infections and infestations	Systematic Assessment	EG0005 affected54 at risk EG0011 affected24 at risk

ID	Term
D000086382	COVID-19
D055371	Acute Lung Injury
D000860	Hypoxia
D045169	Severe Acute Respiratory Syndrome
D012128	Respiratory Distress Syndrome

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D055370	Lung Injury
D012818	Signs and Symptoms, Respiratory
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D012120	Respiration Disorders

ID	Title	Description
BG000	Group A (Active)	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®
BG001	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)
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group A (Active)	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®	7	54	10	54	39	54
EG001	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)	5	24	5	24	17	24