Correlated Drug Terms (3)

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	Name (Synonyms)	Correlation
drug2165	SOC + Placebo Wiki	1.00
drug2164	SOC + Intravenous Famotidine Wiki	1.00
drug1822	Placebo Wiki	0.06

Correlated MeSH Terms (1)

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	Name (Synonyms)	Correlation
D018352	Coronavirus Infections NIH	0.04

Correlated HPO Terms (0)

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	Name (Synonyms)	Correlation

Primary Outcomes

Description: Clinical

Measure: Proportion of patients without any need* for INV until end-of-study (EoS)

Time: Throughout the Study (Day 0 to Day 28)

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Secondary Outcomes

Description: Key Secondary

Measure: Duration of ICU treatment until EoS

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Key Secondary

Measure: 28-day all-cause mortality

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first

Measure: Time to clinical improvement

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)

Measure: Duration of hospitalization

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients free of INV until Days 6 and 14*

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients free of RRT until Days 6 and 14*

Time: Day 0 to Days 6 and 14

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Description: Efficacy

Measure: Proportion of patients free ECMO until Days 6 and 14*

Time: Day 0 to Days 6 and 14

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Description: Efficacy

Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

Time: on Days 6, 14, and 28

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Description: Efficacy

Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28

Time: on Days 6, 14, and 28

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Description: Efficacy

Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃;

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

Time: on Days 6, 14, and 28

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Description: Efficacy

Measure: Duration of INV

Time: Throughout the Study (Day 0 to Day 28 )

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Description: Efficacy

Measure: Duration of ECMO

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Duration of RRT

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy)

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Duration of hospitalization for survivors

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: The rate of ICU* admission on Days 6, 14, and 28

Time: on Days 6, 14, and 28

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Description: Efficacy

Measure: Hospital-free days

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Time from IMP treatment initiation to death

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Time to first prescription of INV

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Time to first prescription of RRT

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Time to first prescription of ECMO

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Time to first prescription of INV, RRT, and ECMO

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Time to ICU admission

Time: Throughout the Study (Day 0 to Day 28)

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Description: Efficacy

Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14)

Time: Day 0 to day 14

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Description: Efficacy

Measure: Time to clinical recovery

Time: Throughout the Study (Day 0 to Day 28)

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Description: Pharmacokinetics

Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28

Time: on Days 0, 1, 2, 3, 6, 14, and 28

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Description: Pharmacokinetics

Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

Time: on Days 0, 1, 2, 3, 6, 14, and 28

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Description: Safety

Measure: Adverse events (AEs) and serious AEs

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: height

Time: only at Screening

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Description: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: weight

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: body temperature (ºC)

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: pulse rates,

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: systolic and diastolic blood pressures

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety

Measure: Clinical laboratory parameters: blood chemistry

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety

Measure: Clinical laboratory parameters: hematology

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety

Measure: Clinical laboratory parameters: urinalysis

Time: Throughout the Study (Day 0 to Day 28)

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Description: Safety

Measure: 12-lead electrocardiogram: heart rate

Time: Day 0 to Day 6 and Day 28

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Description: Safety

Measure: 12-lead electrocardiogram: PQ-interval

Time: Day 0 to Day 6 and Day 28

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Description: Safety

Measure: 12-lead electrocardiogram: QRS-interval

Time: Day 0 to Day 6 and Day 28

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Description: Safety

Measure: 12-lead electrocardiogram: QT interval

Time: Day 0 to Day 6 and Day 28

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Description: Safety

Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula)

Time: Day 0 to Day 6 and Day 28

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Description: Safety

Measure: Temperature

Time: Throughout the Study (Day 0 to Day 28)

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Description: Disease markers

Measure: D-dimer

Time: Throughout the Study (Day 0 to Day 28)

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Description: Disease markers

Measure: Lactate dehydrogenase (LDH)

Time: Throughout the Study (Day 0 to Day 28)

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Description: Disease markers

Measure: C-reactive protein

Time: Throughout the Study (Day 0 to Day 28)

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Description: Disease markers

Measure: Troponin I

Time: Throughout the Study (Day 0 to Day 28)

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Description: Disease markers

Measure: Procalcitonin

Time: Throughout the Study (Day 0 to Day 28)

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Description: Disease markers

Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

Time: Throughout the Study (Day 0 to Day 28)

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Description: Virologic markers

Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load

Time: Throughout the Study (Day 0 to Day 28)

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Description: Virologic markers

Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load

Time: Throughout the Study (Day 0 to Day 28)

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Description: Virologic markers

Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart)

Time: Throughout the Study (Day 0 to Day 28)

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Description: Virologic markers

Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28

Time: on Days 6, 14 and 28

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Description: Virologic markers

Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test

Time: Throughout the Study (Day 0 to Day 28)

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Description: Biomarkers

Measure: Interleukin (IL)-17

Time: Day 0, 6, 14 and Day 28

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Description: Biomarkers

Measure: Interleukin (IL)-1ß

Time: Day 0, 6, 14 and Day 28

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Description: Biomarkers

Measure: Interleukin (IL)-6

Time: Day 0, 6, 14 and 28

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Description: Biomarkers

Measure: interferon gamma (IFNγ)

Time: Day 0, 6, 14 and 28

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Description: Biomarkers

Measure: tumor necrosis factor alpha

Time: Day 0, 6, 14 and 28

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Description: Serologic markers

Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies

Time: Day 0, 6, 14 and 28

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Description: Serologic markers

Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28

Time: Day 0, 6, 14 and 28

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