A Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19 (COVID-19)

A Prospective, Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04379271

Enrollment

234

Registered

2020-05-07

Start date

2020-06-11

Completion date

2021-02-23

Last updated

2024-11-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19

Brief summary

At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.

Detailed description

The trial consists of a Phase 2 proof-of-concept phase (Part 1) with the option to extend enrollment (without interruption) to Phase 3 (Expansion Phase, Part 2). This trial is a multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to evaluate the safety and efficacy of IMU-838 as addition to investigator's choice of SoC treatment in patients with COVID-19. Eligible patients will be centrally randomized 1:1 to twice-daily (BID) oral 22.5 mg IMU-838 (45 mg/day + SoC) or placebo (+ SoC). Randomization will be stratified by age (\< or \>=65 years) and antiviral therapy (no antivirals, Hydroxychloroquine and Chloroquine, all other antivirals). Adaptive sequential trial design and overall trial design The trial uses an adaptive sequential design. An IDMC will review unblinded data and provide the Sponsor with recommendations regarding modifications of sample size and trial conduct. A 1st interim analysis (IA1) will be performed after approximately 200 patients have completed the trial (either as scheduled or prematurely), while enrollment continues. If no activity of IMU 838 is observed by the IDMC in this IA, further patient enrollment will be stopped, and a final analysis of Part 1 will be performed (FA1). It is expected that the final analysis of Part 1 will include approximately 230 patients. If the IA1 results indicate activity of IMU-838 in COVID-19, the trial may be extended to Part 2 with a revised sample size derived by the IDMC based on IA1 results and with possible other trial adjustments. If the trial is extended into Part 2, a 2nd IA (IA2) is planned after approximately two-thirds of patients (based on the overall global sample size \[Part 1 and Part 2 combined\]) have been enrolled to potentially adjust sample size and other trial features if needed. The final analysis of the trial (FA2) will then be done after all patients have completed Part 2. In addition, an early interim safety analysis will be performed and evaluated by the IDMC after 30 patients have been enrolled to assess unblinded safety data. Further safety analyses can be initiated at any time by the IDMC or Sponsor when new safety signals are identified within this or other trials of IMU-838. Screening Patients can be screened for a maximum of 2 days (from Day -2 to Day 0) and eligible patients will be randomized on Day 0 and treated with IMP + SoC for 14 days. It is encouraged to screen potential participants immediately at the day of hospitalization (including informed consent, assessment of inclusion/exclusion criteria, screening laboratory tests all done locally, assessment of clinical and blood gas criteria) and randomize patients on the same day (Day 0). To assess eligibility criteria, existing local laboratory values obtained within 48 hours of randomization can also be used, except for testing of positive status of SARS-CoV-2 infection where a 4-day window is allowed. IMP administration should start as quickly as possible after randomization and first IMP intended to be given in the evening of the screening day (Day 0). Blinded Treatment period (Day 0 to Day 13) and Day 14 (end-of-treatment) The first dose of IMP (2 tablets) should always be given on Day 0 (allowed range for first dose: 12:00 noon on Day 0 to 02:00 a.m.). All further IMP doses are 1 tablet each in the morning and evening. Information about the status and patient care are continuously obtained and documented once or twice daily. After the last IMP dose in the evening of Day 13, the end-of-treatment assessments will be done on Day 14. Blood sampling for IMU-838 trough values must be performed in the morning around the time the morning dose was usually taken by the respective patient. Patients may then continue to receive SoC without any further restrictions on concomitant medications as during the 14-day BT period . Day 28 Visit (EoS) The patient should return for the final trial visit on Day 28 (EoS). If IMP is prematurely discontinued for any reason, the EoS visit should always be conducted on Day 28 and no earlier EoS should be performed. If patients withdraw from IMP prematurely, they should be encouraged to allow the EoS visit as part of the follow-up. If the patient dies during the trial, the investigator should indicate that this visit was not performed. However, even if no EoS visit was performed, information about patient status should be reported on the EoS page in the case report form. If the patient refuses any EoS visit or the patient is lost to follow-up, it is permissive in this trial that the investigator contacts the patient, the family of the patient or the referring physician by phone or email to obtain status of life information, or is able to search in registers or publicly available information for such status of life information.

Interventions

DRUGIMU-838

Tablets will be taken BID with a glass of water (if possible); one tablet each in the morning (15 to 50 min before a meal if applicable), and in the evening (2 hours after any meal if applicable). If the patient is intubated for ventilation, IMP is to be given via a gastric tube. The tablet has no coating and a homogeneous content and can be crushed into smaller pieces (if necessary) for dosing via gastric tube.

OTHERPlacebo

Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for IMU-838

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Trial participants, the investigator and all other personnel directly involved in the conduct of the trial will be blinded to treatment assignments. To maintain the blind, IMU-838 and placebo tablets will have identical appearance, shape and color, and will have identical labeling and packaging. To minimize the potential for bias, treatment randomization information will be kept confidential by the responsible personnel and will not be released to investigators, other trial center personnel, or the Sponsor's designee(s).

Intervention model description

double-blind, placebo-controlled, randomized, parallel-group trial

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Male or female patients at least 18 years old (may be extended to include also children 12 years or older after the 1st interim analysis) 2. Admitted to the hospital or other medical in-patient treatment facility for treatment of COVID-19 The hospitalization needs to be for medical reasons (treatment of COVID-19 disease) and cannot be for social reasons or due to housing insecurity. For US sites only: If the investigator would commonly hospitalize the patient but for healthcare resource reasons decides to treat the patient in a specially designed out-patient setting, then such patients are also allowed to enter the trial (please note that in this case the patient would be counted as clinical status category 3). The investigator then must assure that the patient has at least a twice daily assessment by qualified trial personnel and all laboratory assessments can be adequately performed as per protocol. The Sponsor reserves the right to discontinue this option via administrative letter if such assurances cannot be met by any site. 3. SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) test in a nasopharyngeal, oropharyngeal or respiratory sample at ≤4 days before randomization 4. Moderate COVID-19 disease defined as fulfilling clinical status category 3 or 4 on the WHO 9-point ordinal scale \[21\]: * Category 3: Hospitalized (see note above for US only), virus-positive, no oxygen therapy with the following conditions: * The hospitalization needs to be for medical reasons (treatment of COVID-19 disease) and cannot be for social reasons or due to housing insecurity * Category 4: Hospitalized, virus-positive, oxygen by mask or nasal prongs (excluding high-flow oxygen therapy) with the following conditions: * Peripheral capillary oxyhemoglobin saturation (SpO2) \>92% at maximum of 6 liters oxygen flow per minute * Stable respiratory rate ≤30 breaths/min at maximum of 6 liters oxygen flow per minute 5. Presence of at least 1 symptom characteristic for COVID-19 disease i.e., fever, cough or respiratory distress 6. Willingness and ability to comply with the protocol 7. Written informed consent given prior to any trial-related procedure 8. For women of childbearing potential: Application of a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly) together with a barrier method between trial consent and 30 days after the last intake of the IMP. Highly effective forms of birth control are those with a failure rate less than 1% per year and include: * oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation * oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation * intrauterine device or intrauterine hormone-releasing system * bilateral tubal occlusion * vasectomized partner (i.e., the patient's male partner underwent effective surgical sterilization before the female patient entered the clinical trial and is the sole sexual partner of the female patient during the clinical trial) * sexual abstinence (acceptable only if it is the patient's usual form of birth control/lifestyle choice; periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are no acceptable methods of contraception) Barrier methods of contraception include: * Condom * Occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository 9. Male patients must agree not to father a child or to donate sperm starting at Screening, throughout the clinical trial and for 30 days after the last intake of the IMP. Male patients must also * abstain from sexual intercourse with a female partner (acceptable only if it is the patient's usual form of birth control/lifestyle choice), or * use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and * if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 8 * if they have a pregnant partner, they must use condoms while taking the IMP to avoid exposure of the fetus to the IMP

Exclusion criteria

Underlying disease-related

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Patients Without Any Need for INV Until EoS	Throughout the Study (Day 0 to Day 28)	Number of Participants Stratified as those With and Without the Need for INV Until End-of-study (EoS). For this outcome a worst case approach was used in which patients who were lost to follow-up or who discontinued the trial on or before Day 13 due to any other reason than death and discontinued with a last observed WHO clinical status no lower than that at Screening, and patients who died were considered as patients requiring INV.

Secondary

Measure	Time frame	Description
Vital Signs: Height	at Baseline	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.
Days in ICU Department	Throughout the Study (Day 0 to Day 28 )	Duration of ICU Treatment Until EoS for Only Patients Who Were Admitted to the ICU During the Trial.
All Cause Mortality (ITT Approach)	Throughout the Study (Day 0 to Day 28 )	28-day All-cause Mortality (including lost to follow-up): 'all-cause-mortality' includes all confirmed deaths and patients who discontinued the trial before Day 28 and for whom no outcome (alive or dead) could be determined at EoS; 'actual death' includes only those patients for which a fatal outcome was confirmed by Day 28.
Time to Clinical Improvement	Throughout the Study (Day 0 to Day 28)	Defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the Modified WHO Ordinal Scale for Clinical Status (Modified WHO Ordinal Scale for Clinical Status), or live discharge from hospital without oxygen supplementation, whichever comes first. The 50% Kaplan-Meier quartile (median) of actual values per treatment arm is provided as outcome of this variable below.
Days of Hospitalization	Throughout the Study (Day 0 to Day 28 )	Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)cacy:
Patients Free of Renal-replacement Therapy (RRT)* Until EoS	Throughout the Study (Day 0 to Day 28 )	Number of Patients Both for All Patients and Surviving Patients Free of Renal-replacement Therapy (RRT)\* Until EoS
Patients Required ECMO Until EoS	Throughout the Study (Day 0 to Day 28 )	Number and Percentage of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)\* until EoS.
Vital Signs: Weight	at Baseline	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.
Patients Free of INV Until Day 14*	Throughout the Study (Day 0 to Day 14 )	Number and persentage of patients free of INV until Day 14\*
Patients Free of RRT	Day 0 to Day 14	Percentage of patients free of RRT until Day 14\*
Number of Patients Free of ECMO	Day 0 to Day 14	Number of patients free of ECMO until Day 14.
Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	on Days 6, 14, and 28	Numbers of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1( Modified WHO Ordinal Scale for Clinical Status)on Days 6, 14, and 28, where score 0 means no clinical or virological evidence of infection and score 8 is the worth outcome ( mens death).
Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	on Days 6, 14, and 28	Percentage of Patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28.
Patients With Clinical Recovery	Throughout the Study (Day 0 to Day 28 )	Percentage of Patients With Clinical Recovery: Axillary Temp \<= 36.6 °C, or Oral Temp \<= 37.2 °C, or Rectal or Tympanic Temp \<= 37.8 °C and Respiratory Frequency \<= 24 Times/Min Without O2 Inhalation and O2 Saturation \>= 98% Without O2 Inhalation
Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation	Throughout the Study (Day 0 to Day 28 )	Percentage 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 (Modified WHO Ordinal Scale for Clinical Status, where score 0 - for patient with no clinical or virological evidence of infections, score 9 - the worth scenario- death)
Percentage of Participants With WHO Status<=2	on Days 6, 14, and 28	Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28
Duration of INV	Throughout the Study (Day 0 to Day 28 )	Duration of INV throughout the study. If no entry on the respective CRF page exists, the duration is set to 0 days for patients who performed Day 28 visit. Patients without Day 28 visit and without any entry on the respective CRF page are excluded from analysis.
Days on ECMO	Throughout the Study (Day 0 to Day 28)	Duration of ECMO in days (duration set to 0 for those who did not require ECMO). No participants required ECMO.
Days on RRT	Throughout the Study (Day 0 to Day 28)	Duration of RRT in days (duration set to 0 for those who did not require RRT).No participants required RRT.
Days of Auxiliary Oxygen Therapy	Throughout the Study (Day 0 to Day 28)	Duration of auxiliary oxygen therapy (including all types of oxygen therapy)
Vital Signs: Body Temperature (ºC)	at Baseline	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.
Albumin Concentration at Various Time Points	Throughout the Study (Day 0 to Day 28)	Clinical laboratory parameters: blood chemistry (Albumin concentration at various time points)
Hematocrit Ratio at Various Time Points	Throughout the Study (Day 0 to Day 28)	Clinical laboratory parameters: hematology- Hematocrit ratio at various time points
Urine Creatinine at Various Time Points	Throughout the Study (Day 0 to Day 28)	Clinical laboratory parameters: urinalysis- Urine creatinine at various time points
Temperature	Throughout the Study (Day 0 to Day 28)	Temperature data at different time point.
D-dimer	Throughout the Study (Day 0 to Day 28)	Disease markers
Participants With ICU Admission	on Days 6, 14, and 28	Percentage of Participants with ICU Admission at different time point
Probability of Death	Throughout the Study (Day 0 to Day 28)	Probability of death derived from Kaplan Meier analyses
Days to INV	Throughout the Study (Day 0 to Day 28)	Time to first prescription of invasive ventilation (INV). The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.
Days to RRT	Throughout the Study (Day 0 to Day 28)	Time to first prescription of RRT
Days to ECMO	Throughout the Study (Day 0 to Day 28)	Time to first prescription of ECMO
Days to INV, RRT and ECMO	Throughout the Study (Day 0 to Day 28)	Time to first prescription of INV, RRT, and ECMO. The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.
Probability of ICU Admission	Throughout the Study (Day 0 to Day 28)	Overall probability of ICU admission derived from Kaplan Meier analyses.
Cumulative Dose	Day 0 to day 14	Cumulative Dose of Vasoactive Therapies and Days With Vasoactive Therapies (Daily Until Day 14)
Time to Clinical Recovery	Throughout the Study (Day 0 to EoS [Day 27 up to Day 42])	Time of first assessments of parameters contributing to clinical recovery
Plasma Levels of IMU-838	on Days 0, 1, 2, 3, 6, 14, and 28	Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28
Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Trough levels at Day 14; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)	Kaplan-Meier analyses were used to investigate a potential relationship between trough plasma levels of IMU-838 and time to clinical improvement and time to clinical recovery. Estimates of the clinical outcomes were evaluated separately for patients within each of the four quartiles of IMU-838 trough levels at Day 14.
Number of Participants With Adverse Events (AEs) and Serious AEs	Throughout the Study (Day 0 to Day 28)	Adverse events (AEs) and serious AEs. AEs-Hypertriglyceridemia,Increased glycosylated hemoglobin, Headache, Thrombocytosis, Hyperglycemia, AEs reported in ≥ 2.0% of patients in any treatment group included anemia, bradycardia, sinus bradycardia, tachycardia, pyrexia, hepatocellular injury, hematuria, hypertension and hypertensive crisis. SAEs- deep vein thrombosis,COVID-19 pneumonia, patient death.
C-reactive Protein	Throughout the Study (Day 0 to Day 28)	Blood levels of disease markers
Troponin I	Throughout the Study (Day 0 to Day 28)	Bood levels of disease markers
Procalcitonin	Throughout the Study (Day 0 to Day 28)	Blood levels of disease markers
Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	D-Dimer levels at Day 6; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)	Kaplan-Meier analyses were used to investigate a potential relationship between blood levels of D-Dimer and time to clinical improvement. Estimates of the clinical outcome were evaluated separately for patients within each of the four quartiles of D-Dimer levels at Day 6.
Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Throughout the Study (Day 0 to Day 28)	Virologic markers: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples: changing of SARS-CoV-2 Viral Load in patients on Days 6,14,28
Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Throughout the Study (Day 0 to Day 28)	Virologic markers :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
Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart	Throughout the Study (Day 0 to Day 28)	Virologic markers: 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)
Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test	on Day 28	Virologic markers: conversion to a negative SARS-CoV-2 (qualitative) test on Day 28.
Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test	Throughout the Study (Day 0 to Day 28)	Virologic markers : Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test Throughout the study. Only patients with viral load measured from nasopharyngeal swab and results provided by the central laboratory (Covance) were included.Conversion to a negative SARS-CoV-2 status is only assumed if a negative test is confirmed by all available subsequent assessments. This means for Day 28/early termination visit no confirmation is needed. If no conversion to a negative status is documented, patients will be censored for survival analysis at the time of the last documented positive test result.
Lactate Dehydrogenase (LDH)	Throughout the Study (Day 0 to Day 28)	Blood levels of disease markers
Interleukin (IL)-1ß	Day 0, 6, 14 and Day 28	The profiles of immune system biomarkers
Interleukin (IL)-6	Day 0, 6, 14 and 28	The profiles of immune system biomarkers
Interferon Gamma (IFNγ)	Day 0, 6, 14 and 28	The profiles of immune system biomarkers
Tumor Necrosis Factor Alpha	Day 0, 6, 14 and 28	The profiles of immune system biomarkers
Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 6, 14 and 28	Proportion of patients with IgA and/or IgG antibodies against SARS-CoV-2on at different time point
Interleukin (IL)-17	Day 0, 6, 14 and Day 28	The profiles of immune system biomarkers

Countries

Bulgaria, Germany

Participant flow

Pre-assignment details

223 patients were randomized; 220 patients were treated and included in the full analysis and safety data set (110 patients each in the 45 mg IMU-838 group and the placebo group).

Participants by arm

Arm	Count
IMU-838 twice-daily (BID) oral 22.5 mg IMU-838 (45 mg/day + SoC) IMU-838: Tablets will be taken BID with a glass of water (if possible); one tablet each in the morning (15 to 50 min before a meal if applicable), and in the evening (2 hours after any meal if applicable). If the patient is intubated for ventilation, IMP is to be given via a gastric tube. The tablet has no coating and a homogeneous content and can be crushed into smaller pieces (if necessary) for dosing via gastric tube.	110
Placebo twice-daily (BID) oral placebo (+ SoC) Placebo: Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for IMU-838	110
Total	220

Baseline characteristics

Characteristic	IMU-838	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	27 Participants	27 Participants	54 Participants
Age, Categorical Between 18 and 65 years	83 Participants	83 Participants	166 Participants
Age, Continuous	54.5 years STANDARD_DEVIATION 13.4	53.7 years STANDARD_DEVIATION 14.2	54.1 years STANDARD_DEVIATION 13.8
Race/Ethnicity, Customized Race Asian	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race Black or African American	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race Other	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race White	110 Participants	107 Participants	217 Participants
Sex: Female, Male Female	55 Participants	46 Participants	101 Participants
Sex: Female, Male Male	55 Participants	64 Participants	119 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 110	2 / 110
other Total, other adverse events	79 / 110	65 / 110
serious Total, serious adverse events	2 / 110	4 / 110

Outcome results

Primary

Proportion of Patients Without Any Need for INV Until EoS

Number of Participants Stratified as those With and Without the Need for INV Until End-of-study (EoS). For this outcome a worst case approach was used in which patients who were lost to follow-up or who discontinued the trial on or before Day 13 due to any other reason than death and discontinued with a last observed WHO clinical status no lower than that at Screening, and patients who died were considered as patients requiring INV.

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

Population: FAS, Full Analysis Set

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Proportion of Patients Without Any Need for INV Until EoS	No INV needed	98 Participants
IMU-838	Proportion of Patients Without Any Need for INV Until EoS	INV needed	12 Participants
Placebo	Proportion of Patients Without Any Need for INV Until EoS	No INV needed	101 Participants
Placebo	Proportion of Patients Without Any Need for INV Until EoS	INV needed	9 Participants

Secondary

Albumin Concentration at Various Time Points

Clinical laboratory parameters: blood chemistry (Albumin concentration at various time points)

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

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Albumin Concentration at Various Time Points	Day 28	44.0 g/L	Standard Deviation 3.7
IMU-838	Albumin Concentration at Various Time Points	Baseline	39.4 g/L	Standard Deviation 4.4
IMU-838	Albumin Concentration at Various Time Points	Day 6	37.9 g/L	Standard Deviation 4.2
IMU-838	Albumin Concentration at Various Time Points	Day 14	39.6 g/L	Standard Deviation 4.6
Placebo	Albumin Concentration at Various Time Points	Day 14	40.3 g/L	Standard Deviation 4.6
Placebo	Albumin Concentration at Various Time Points	Day 28	44.0 g/L	Standard Deviation 4.4
Placebo	Albumin Concentration at Various Time Points	Day 6	38.7 g/L	Standard Deviation 4.9
Placebo	Albumin Concentration at Various Time Points	Baseline	40.2 g/L	Standard Deviation 4.7

Secondary

All Cause Mortality (ITT Approach)

28-day All-cause Mortality (including lost to follow-up): 'all-cause-mortality' includes all confirmed deaths and patients who discontinued the trial before Day 28 and for whom no outcome (alive or dead) could be determined at EoS; 'actual death' includes only those patients for which a fatal outcome was confirmed by Day 28.

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
IMU-838	All Cause Mortality (ITT Approach)	actual death	2 Participants
IMU-838	All Cause Mortality (ITT Approach)	28 days all cause mortality (including lost to follow-up)	9 Participants
Placebo	All Cause Mortality (ITT Approach)	actual death	2 Participants
Placebo	All Cause Mortality (ITT Approach)	28 days all cause mortality (including lost to follow-up)	8 Participants

Secondary

Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points

Virologic markers: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples: changing of SARS-CoV-2 Viral Load in patients on Days 6,14,28

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

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 2	-10020591.1 Change in log10 copies	Standard Deviation 38272166.5
IMU-838	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 28	-15195922.3 Change in log10 copies	Standard Deviation 54087022.5
IMU-838	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 6	-12849771.3 Change in log10 copies	Standard Deviation 49984377.5
IMU-838	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 14	-13617000.9 Change in log10 copies	Standard Deviation 51579374.1
Placebo	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 14	-89534493.9 Change in log10 copies	Standard Deviation 429884542.5
Placebo	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 2	-62534293.5 Change in log10 copies	Standard Deviation 380490492.5
Placebo	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 6	-84355538.5 Change in log10 copies	Standard Deviation 416667915.1
Placebo	Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points	Day 28	-44774028.6 Change in log10 copies	Standard Deviation 249373454.1

Secondary

Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6

Kaplan-Meier analyses were used to investigate a potential relationship between blood levels of D-Dimer and time to clinical improvement. Estimates of the clinical outcome were evaluated separately for patients within each of the four quartiles of D-Dimer levels at Day 6.

Time frame: D-Dimer levels at Day 6; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)

Population: Safety analysis set consisting of all randomized patients who received at least one dose of IMP.

Arm	Measure	Group	Value (MEDIAN)
IMU-838	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 1 (Min to 275 ng/mL D-Dimer)	13.8 days
IMU-838	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 2 (275 to 450 ng/mL D-Dimer)	13.7 days
IMU-838	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 3 (450 to 731 ng/mL D-Dimer)	13.8 days
IMU-838	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 4 (731 ng/mL to Max D-Dimer)	13.7 days
Placebo	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 2 (275 to 450 ng/mL D-Dimer)	13.8 days
Placebo	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 1 (Min to 275 ng/mL D-Dimer)	13.8 days
Placebo	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 3 (450 to 731 ng/mL D-Dimer)	13.8 days
Placebo	Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6	Q 4 (731 ng/mL to Max D-Dimer)	13.8 days

Secondary

Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes

Kaplan-Meier analyses were used to investigate a potential relationship between trough plasma levels of IMU-838 and time to clinical improvement and time to clinical recovery. Estimates of the clinical outcomes were evaluated separately for patients within each of the four quartiles of IMU-838 trough levels at Day 14.

Time frame: Trough levels at Day 14; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)

Population: The safety analysis set consisting of all randomized patients who received at least one dose of IMU-838.

Arm	Measure	Group	Value (MEDIAN)
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical improvement - Q2 (3.1 to 4.2 µg/mL IMU-838)	13.8 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical recovery - Q1 (Min to 3.1 µg/mL IMU-838)	27.8 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical recovery - Q2 (3.1 to 4.2 µg/mL IMU-838)	27.9 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical recovery - Q3 (4.2 to 6.0 µg/mL IMU-838)	11.8 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical recovery - Q4 (6.0 µg/mL to Max IMU-838)	11.3 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical improvement - Q1 (Min to 3.1 µg/mL IMU-838)	13.7 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical improvement - Q3 (4.2 to 6.0 µg/mL IMU-838)	13.7 days
IMU-838	Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes	Time to clinical improvement - Q4 (6.0 µg/mL to Max IMU-838)	13.7 days

Secondary

C-reactive Protein

Blood levels of disease markers

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

Arm	Measure	Group	Value (MEDIAN)
IMU-838	C-reactive Protein	Baseline	320.4826 nmol/L
IMU-838	C-reactive Protein	Day 14	27.61960 nmol/L
IMU-838	C-reactive Protein	Day 28	23.81000 nmol/L
Placebo	C-reactive Protein	Baseline	245.2430 nmol/L
Placebo	C-reactive Protein	Day 14	20.95280 nmol/L
Placebo	C-reactive Protein	Day 28	16.19080 nmol/L

Secondary

Cumulative Dose

Cumulative Dose of Vasoactive Therapies and Days With Vasoactive Therapies (Daily Until Day 14)

Time frame: Day 0 to day 14

Population: Vasoactive therapy was prescribed for only 1 patient in the IMU-838 group for a single day . If no vasoactive therapy was given, cumulative dose is set to 0.

Arm	Measure	Value (MEAN)
IMU-838	Cumulative Dose	0 mg

Secondary

Days in ICU Department

Duration of ICU Treatment Until EoS for Only Patients Who Were Admitted to the ICU During the Trial.

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
IMU-838	Days in ICU Department	2.54 days	Standard Deviation 7.24
Placebo	Days in ICU Department	2.33 days	Standard Deviation 7.24

Secondary

Days of Auxiliary Oxygen Therapy

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

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

Population: 106 and 107 participants respectively were studied. Only participants who required auxiliary oxygen therapy were selected. If auxiliary oxygen therapy started before randomization, time of randomization is used as start time.Patients who are lost to follow-up or discontinue prematurely without Day 28 and without any auxiliary oxygen therapy documented are excluded from analysis.

Arm	Measure	Value (MEAN)	Dispersion
IMU-838	Days of Auxiliary Oxygen Therapy	4.49 days	Standard Deviation 7.01
Placebo	Days of Auxiliary Oxygen Therapy	3.86 days	Standard Deviation 7.26

Secondary

Days of Hospitalization

Duration of hospitalization for survivors

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

Population: Patients enrolled in centers in Bulgaria (N = 37 in the 45 mg IMU-838 group and N = 33 in the placebo group) were excluded from the analysis as, per protocol, they were required to remain hospitalized for the entire treatment period

Arm	Measure	Value (MEAN)
IMU-838	Days of Hospitalization	13.53 days
Placebo	Days of Hospitalization	14.52 days

Secondary

Days of Hospitalization

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

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

Population: Patients from Bulgaria were excluded because they had to stay in hospital for the entire treatment period as per protocol.

Arm	Measure	Value (MEAN)	Dispersion
IMU-838	Days of Hospitalization	13.49 days	Standard Deviation 7
Placebo	Days of Hospitalization	14.35 days	Standard Deviation 7.71

Secondary

Days on ECMO

Duration of ECMO in days (duration set to 0 for those who did not require ECMO). No participants required ECMO.

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

Population: patients, who require ECMO throughout the study

Arm	Measure	Value (NUMBER)
IMU-838	Days on ECMO	0 days
Placebo	Days on ECMO	0 days

Secondary

Days on RRT

Duration of RRT in days (duration set to 0 for those who did not require RRT).No participants required RRT.

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

Population: patients , who require RRT throughout the study

Arm	Measure	Value (NUMBER)
IMU-838	Days on RRT	0 days
Placebo	Days on RRT	0 days

Secondary

Days to ECMO

Time to first prescription of ECMO

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

Population: No patients required ECMO during the trial

Secondary

Days to INV

Time to first prescription of invasive ventilation (INV). The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.

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

Population: Only 2 patients had confirmed use of INV throughout the study and were included in the analysis.

Arm	Measure	Value (MEDIAN)
IMU-838	Days to INV	13.8 days
Placebo	Days to INV	6.0 days

Secondary

Days to INV, RRT and ECMO

Time to first prescription of INV, RRT, and ECMO. The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.

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

Population: Only 2 patients had confirmed use of INV throughout the study and were included in the analysis. No patients required RRT or ECMO during the trial.

Arm	Measure	Value (MEDIAN)
IMU-838	Days to INV, RRT and ECMO	13.8 days
Placebo	Days to INV, RRT and ECMO	6.0 days

Secondary

Days to RRT

Time to first prescription of RRT

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

Population: No patients required RRT during the trial

Secondary

D-dimer

Disease markers

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

Arm	Measure	Group	Value (MEDIAN)
IMU-838	D-dimer	Baseline	529.5 ng/mL
IMU-838	D-dimer	Day 14	348.0 ng/mL
IMU-838	D-dimer	Day 28	343.0 ng/mL
Placebo	D-dimer	Baseline	473.0 ng/mL
Placebo	D-dimer	Day 14	357.0 ng/mL
Placebo	D-dimer	Day 28	332.5 ng/mL

Secondary

Duration of INV

Duration of INV throughout the study. If no entry on the respective CRF page exists, the duration is set to 0 days for patients who performed Day 28 visit. Patients without Day 28 visit and without any entry on the respective CRF page are excluded from analysis.

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

Population: Patients who are lost to follow-up or discontinued the trial on or before Day 13 (last treatment day) due to any other reason than death and discontinue with a last observed WHO clinical status, and patients who die before Day 28 will be considered treatment failures (i.e. having a need for INV) for the primary endpoint.

Arm	Measure	Value (MEAN)
IMU-838	Duration of INV	0.00 days
Placebo	Duration of INV	0.07 days

Secondary

Hematocrit Ratio at Various Time Points

Clinical laboratory parameters: hematology- Hematocrit ratio at various time points

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

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Hematocrit Ratio at Various Time Points	Baseline	0.435 ratio	Standard Deviation 0.052
IMU-838	Hematocrit Ratio at Various Time Points	Day 6	0.430 ratio	Standard Deviation 0.059
IMU-838	Hematocrit Ratio at Various Time Points	Day 14	0.435 ratio	Standard Deviation 0.049
IMU-838	Hematocrit Ratio at Various Time Points	Day 28	0.428 ratio	Standard Deviation 0.046
Placebo	Hematocrit Ratio at Various Time Points	Day 28	0.432 ratio	Standard Deviation 0.052
Placebo	Hematocrit Ratio at Various Time Points	Baseline	0.448 ratio	Standard Deviation 0.053
Placebo	Hematocrit Ratio at Various Time Points	Day 14	0.440 ratio	Standard Deviation 0.051
Placebo	Hematocrit Ratio at Various Time Points	Day 6	0.443 ratio	Standard Deviation 0.053

Secondary

Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2

Proportion of patients with IgA and/or IgG antibodies against SARS-CoV-2on at different time point

Time frame: Day 6, 14 and 28

Population: Not all 220 patients were negative for SARS-CoV-2 in nasopharyngeal samples analyzed by the central laboratory throughout the study. Patients, where the reported result for IgA and IgG antibodies is limit, are considered as negative for analysis.

Arm	Measure	Group	Value (NUMBER)
IMU-838	Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 6	86.0 percent of patients
IMU-838	Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 14	96.9 percent of patients
IMU-838	Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 28	98.3 percent of patients
Placebo	Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 6	83.8 percent of patients
Placebo	Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 14	94.3 percent of patients
Placebo	Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2	Day 28	96.9 percent of patients

Secondary

Interferon Gamma (IFNγ)

The profiles of immune system biomarkers

Time frame: Day 0, 6, 14 and 28

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Interferon Gamma (IFNγ)	Baseline	94.364 pg/mL	Standard Deviation 166.465
IMU-838	Interferon Gamma (IFNγ)	Day 6	28.654 pg/mL	Standard Deviation 90.127
IMU-838	Interferon Gamma (IFNγ)	Day 14	10.469 pg/mL	Standard Deviation 13.224
IMU-838	Interferon Gamma (IFNγ)	Day 28	17.013 pg/mL	Standard Deviation 33.762
Placebo	Interferon Gamma (IFNγ)	Day 28	14.452 pg/mL	Standard Deviation 21.067
Placebo	Interferon Gamma (IFNγ)	Baseline	92.190 pg/mL	Standard Deviation 153.798
Placebo	Interferon Gamma (IFNγ)	Day 14	38.192 pg/mL	Standard Deviation 150.623
Placebo	Interferon Gamma (IFNγ)	Day 6	24.141 pg/mL	Standard Deviation 77.85

Secondary

Interleukin (IL)-17

The profiles of immune system biomarkers

Time frame: Day 0, 6, 14 and Day 28

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Interleukin (IL)-17	Baseline	5.860 pg/mL	Standard Deviation 0
IMU-838	Interleukin (IL)-17	Day 6	5.860 pg/mL	Standard Deviation 0
IMU-838	Interleukin (IL)-17	Day 14	5.924 pg/mL	Standard Deviation 0.621
IMU-838	Interleukin (IL)-17	Day 28	5.866 pg/mL	Standard Deviation 0.058
Placebo	Interleukin (IL)-17	Day 28	5.892 pg/mL	Standard Deviation 0.308
Placebo	Interleukin (IL)-17	Baseline	5.860 pg/mL	Standard Deviation 0
Placebo	Interleukin (IL)-17	Day 14	5.860 pg/mL	Standard Deviation 0
Placebo	Interleukin (IL)-17	Day 6	5.885 pg/mL	Standard Deviation 0.177

Secondary

Interleukin (IL)-1ß

The profiles of immune system biomarkers

Time frame: Day 0, 6, 14 and Day 28

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Interleukin (IL)-1ß	Baseline	0.668 ng/L	Standard Deviation 0.159
IMU-838	Interleukin (IL)-1ß	Day 6	1.014 ng/L	Standard Deviation 1.865
IMU-838	Interleukin (IL)-1ß	Day 14	0.976 ng/L	Standard Deviation 1.955
IMU-838	Interleukin (IL)-1ß	Day 28	0.984 ng/L	Standard Deviation 2.24
Placebo	Interleukin (IL)-1ß	Day 28	0.662 ng/L	Standard Deviation 0.076
Placebo	Interleukin (IL)-1ß	Baseline	0.654 ng/L	Standard Deviation 0.032
Placebo	Interleukin (IL)-1ß	Day 14	0.862 ng/L	Standard Deviation 0.97
Placebo	Interleukin (IL)-1ß	Day 6	1.100 ng/L	Standard Deviation 2.165

Secondary

Interleukin (IL)-6

The profiles of immune system biomarkers

Time frame: Day 0, 6, 14 and 28

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Interleukin (IL)-6	Day 14	7.697 ng/L	Standard Deviation 25.514
IMU-838	Interleukin (IL)-6	Baseline	6.217 ng/L	Standard Deviation 8.037
IMU-838	Interleukin (IL)-6	Day 28	3.437 ng/L	Standard Deviation 14.317
IMU-838	Interleukin (IL)-6	Day 6	5.441 ng/L	Standard Deviation 14.271
Placebo	Interleukin (IL)-6	Day 28	1.468 ng/L	Standard Deviation 1.879
Placebo	Interleukin (IL)-6	Baseline	5.093 ng/L	Standard Deviation 6.438
Placebo	Interleukin (IL)-6	Day 14	5.536 ng/L	Standard Deviation 26.081
Placebo	Interleukin (IL)-6	Day 6	8.435 ng/L	Standard Deviation 30.854

Secondary

Lactate Dehydrogenase (LDH)

Blood levels of disease markers

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

Arm	Measure	Group	Value (MEDIAN)
IMU-838	Lactate Dehydrogenase (LDH)	Day 28	3375.5 nkat/L
IMU-838	Lactate Dehydrogenase (LDH)	Baseline	4176.0 nkat/L
IMU-838	Lactate Dehydrogenase (LDH)	Day 14	3167.0 nkat/L
Placebo	Lactate Dehydrogenase (LDH)	Day 28	3267.0 nkat/L
Placebo	Lactate Dehydrogenase (LDH)	Baseline	4059.0 nkat/L
Placebo	Lactate Dehydrogenase (LDH)	Day 14	3117.0 nkat/L

Secondary

Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples

Virologic markers :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 frame: Throughout the Study (Day 0 to Day 28)

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Baseline	10966569.9 log10 Copies	Standard Deviation 46215130.5
IMU-838	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Day 14	37642.6 log10 Copies	Standard Deviation 281630.2
IMU-838	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Day 6	33277.7 log10 Copies	Standard Deviation 168585.9
IMU-838	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Day 28	181.6 log10 Copies	Standard Deviation 673.9
Placebo	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Day 6	581813.6 log10 Copies	Standard Deviation 3313425.6
Placebo	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Baseline	75572844.7 log10 Copies	Standard Deviation 389541813.1
Placebo	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Day 28	369.7 log10 Copies	Standard Deviation 2133.1
Placebo	Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples	Day 14	483522.2 log10 Copies	Standard Deviation 3851254.5

Secondary

Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart

Virologic markers: 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 frame: Throughout the Study (Day 0 to Day 28)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart	69 Participants
Placebo	Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart	77 Participants

Secondary

Number of Participants With Adverse Events (AEs) and Serious AEs

Adverse events (AEs) and serious AEs. AEs-Hypertriglyceridemia,Increased glycosylated hemoglobin, Headache, Thrombocytosis, Hyperglycemia, AEs reported in ≥ 2.0% of patients in any treatment group included anemia, bradycardia, sinus bradycardia, tachycardia, pyrexia, hepatocellular injury, hematuria, hypertension and hypertensive crisis. SAEs- deep vein thrombosis,COVID-19 pneumonia, patient death.

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Number of Participants With Adverse Events (AEs) and Serious AEs	Any AE	81 Participants
IMU-838	Number of Participants With Adverse Events (AEs) and Serious AEs	Any serious AE	2 Participants
Placebo	Number of Participants With Adverse Events (AEs) and Serious AEs	Any AE	69 Participants
Placebo	Number of Participants With Adverse Events (AEs) and Serious AEs	Any serious AE	4 Participants

Secondary

Number of Patients Free of ECMO

Number of patients free of ECMO until Day 14.

Time frame: Day 0 to Day 14

Population: If ECMO was prescribed but was not started, the patient is considered as being not free of ECMO.~Patients with ECMO documented are included with 'no' in analysis of all following visits (irrespective of whether visit was done). Patients without ECMO documented are excluded from analysis of visits after their last performed visit.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Number of Patients Free of ECMO	110 Participants
Placebo	Number of Patients Free of ECMO	110 Participants

Secondary

Participants With ICU Admission

Percentage of Participants with ICU Admission at different time point

Time frame: on Days 6, 14, and 28

Population: Patients without ICU documented were excluded from analysis of visits after their last performed visit.

Arm	Measure	Group	Value (NUMBER)
IMU-838	Participants With ICU Admission	Day 6	3.7 percent of patients
IMU-838	Participants With ICU Admission	Day 14	3.8 percent of patients
IMU-838	Participants With ICU Admission	Day 28	4.0 percent of patients
Placebo	Participants With ICU Admission	Day 6	3.8 percent of patients
Placebo	Participants With ICU Admission	Day 14	5.0 percent of patients
Placebo	Participants With ICU Admission	Day 28	5.0 percent of patients

Secondary

Patients Free of INV Until Day 14*

Number and persentage of patients free of INV until Day 14\*

Time frame: Throughout the Study (Day 0 to Day 14 )

Population: Patients without INV documented in group IMU-838 and Placebo group ( 7 and 10 accordingly) were excluded from analysis of visits after their last performed visit

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Patients Free of INV Until Day 14*	102 Participants
Placebo	Patients Free of INV Until Day 14*	99 Participants

Secondary

Patients Free of Renal-replacement Therapy (RRT)* Until EoS

Number of Patients Both for All Patients and Surviving Patients Free of Renal-replacement Therapy (RRT)\* Until EoS

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Patients Free of Renal-replacement Therapy (RRT)* Until EoS	110 Participants
Placebo	Patients Free of Renal-replacement Therapy (RRT)* Until EoS	110 Participants

Secondary

Patients Free of RRT

Percentage of patients free of RRT until Day 14\*

Time frame: Day 0 to Day 14

Population: Patients without RRT documented are excluded from analysis of visits after their last performed visit.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Patients Free of RRT	110 Participants
Placebo	Patients Free of RRT	110 Participants

Secondary

Patients Required ECMO Until EoS

Number and Percentage of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)\* until EoS.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Patients Required ECMO Until EoS	0 Participants
Placebo	Patients Required ECMO Until EoS	0 Participants

Secondary

Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)

Percentage of Patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28.

Time frame: on Days 6, 14, and 28

Population: Patients without axillary oxygen therapy documented were excluded from analysis of visits after their last performed visit. Numbers of participants analyzed changed across time points.

Arm	Measure	Group	Value (NUMBER)
IMU-838	Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	Day 6	47.2 percentage of participants
IMU-838	Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	Day 14	47.7 percentage of participants
IMU-838	Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	Day 28	48.1 percentage of participants
Placebo	Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	Day 6	40.7 percentage of participants
Placebo	Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	Day 14	41.1 percentage of participants
Placebo	Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)	Day 28	42.1 percentage of participants

Secondary

Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation

Percentage 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 (Modified WHO Ordinal Scale for Clinical Status, where score 0 - for patient with no clinical or virological evidence of infections, score 9 - the worth scenario- death)

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

Population: One patient from group IMU-838 was excluded from this analysis due to hospital discharge before start of treatment.

Arm	Measure	Value (NUMBER)
IMU-838	Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation	91.7 percent of patients
Placebo	Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation	88.2 percent of patients

Secondary

Patients With Clinical Recovery

Percentage of Patients With Clinical Recovery Oxygen Saturation ≥98% Without Oxygen Inhalation

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

Arm	Measure	Group	Value (NUMBER)
IMU-838	Patients With Clinical Recovery	Day 7	17.4 percent of patients
IMU-838	Patients With Clinical Recovery	Day 14	40.2 percent of patients
IMU-838	Patients With Clinical Recovery	Day 28	69.3 percent of patients
Placebo	Patients With Clinical Recovery	Day 7	12.0 percent of patients
Placebo	Patients With Clinical Recovery	Day 14	45.8 percent of patients
Placebo	Patients With Clinical Recovery	Day 28	65.6 percent of patients

Secondary

Patients With Clinical Recovery

Percentage of Patients With Clinical Recovery: Axillary Temp \<= 36.6 °C, or Oral Temp \<= 37.2 °C, or Rectal or Tympanic Temp \<= 37.8 °C and Respiratory Frequency \<= 24 Times/Min Without O2 Inhalation and O2 Saturation \>= 98% Without O2 Inhalation

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

Population: Clinical recovery was only assumed if it was confirmed in the evening and at the next visit.

Arm	Measure	Group	Value (NUMBER)
IMU-838	Patients With Clinical Recovery	Day 0	5.5 percent of patients
IMU-838	Patients With Clinical Recovery	Day 7	17.4 percent of patients
IMU-838	Patients With Clinical Recovery	Day 14	40.2 percent of patients
IMU-838	Patients With Clinical Recovery	Baseline	3.7 percent of patients
IMU-838	Patients With Clinical Recovery	Day 10	21.7 percent of patients
IMU-838	Patients With Clinical Recovery	Day 28	69.3 percent of patients
Placebo	Patients With Clinical Recovery	Day 14	45.8 percent of patients
Placebo	Patients With Clinical Recovery	Day 0	3.7 percent of patients
Placebo	Patients With Clinical Recovery	Baseline	3.6 percent of patients
Placebo	Patients With Clinical Recovery	Day 7	12.0 percent of patients
Placebo	Patients With Clinical Recovery	Day 10	19.5 percent of patients
Placebo	Patients With Clinical Recovery	Day 28	65.6 percent of patients

Secondary

Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1

Numbers of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1( Modified WHO Ordinal Scale for Clinical Status)on Days 6, 14, and 28, where score 0 means no clinical or virological evidence of infection and score 8 is the worth outcome ( mens death).

Time frame: on Days 6, 14, and 28

Arm	Measure	Group	Value (NUMBER)
IMU-838	Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	Day 28	95 participants
IMU-838	Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	Day 6	5 participants
IMU-838	Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	Day 14	44 participants
Placebo	Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	Day 6	5 participants
Placebo	Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	Day 14	39 participants
Placebo	Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1	Day 28	93 participants

Secondary

Percentage of Participants With WHO Status<=2

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

Time frame: on Days 6, 14, and 28

Population: Missing data

Arm	Measure	Group	Value (NUMBER)
IMU-838	Percentage of Participants With WHO Status<=2	Day 14	48.5 percentage of patients, WHO status <=2
IMU-838	Percentage of Participants With WHO Status<=2	Day 28	97.9 percentage of patients, WHO status <=2
IMU-838	Percentage of Participants With WHO Status<=2	Day 6	6.3 percentage of patients, WHO status <=2
Placebo	Percentage of Participants With WHO Status<=2	Day 14	44.3 percentage of patients, WHO status <=2
Placebo	Percentage of Participants With WHO Status<=2	Day 6	5.1 percentage of patients, WHO status <=2
Placebo	Percentage of Participants With WHO Status<=2	Day 28	96.9 percentage of patients, WHO status <=2

Secondary

Plasma Levels of IMU-838

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

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

Population: Placebo group not available

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Plasma Levels of IMU-838	Day 1	2.9234 ug/mL	Standard Deviation 1.1493
IMU-838	Plasma Levels of IMU-838	Day 2	3.5724 ug/mL	Standard Deviation 1.6299
IMU-838	Plasma Levels of IMU-838	Day 3	3.8572 ug/mL	Standard Deviation 1.8606
IMU-838	Plasma Levels of IMU-838	Day 6	4.3607 ug/mL	Standard Deviation 2.4872
IMU-838	Plasma Levels of IMU-838	Day 14	4.6514 ug/mL	Standard Deviation 2.6506
IMU-838	Plasma Levels of IMU-838	Day 28	0.1014 ug/mL	Standard Deviation 0.0093
IMU-838	Plasma Levels of IMU-838	Baseline	0.1108 ug/mL	Standard Deviation 0.1135

Secondary

Probability of Death

Probability of death derived from Kaplan Meier analyses

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

Arm	Measure	Value (NUMBER)
IMU-838	Probability of Death	0.019 Probability
Placebo	Probability of Death	0.019 Probability

Secondary

Probability of ICU Admission

Overall probability of ICU admission derived from Kaplan Meier analyses.

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

Arm	Measure	Value (NUMBER)
IMU-838	Probability of ICU Admission	0.037 Probability
Placebo	Probability of ICU Admission	0.047 Probability

Secondary

Procalcitonin

Blood levels of disease markers

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

Arm	Measure	Group	Value (MEDIAN)
IMU-838	Procalcitonin	Day 28	0.0380 ng/mL
IMU-838	Procalcitonin	Baseline	0.0695 ng/mL
IMU-838	Procalcitonin	Day 14	0.0410 ng/mL
Placebo	Procalcitonin	Day 14	0.0340 ng/mL
Placebo	Procalcitonin	Day 28	0.0350 ng/mL
Placebo	Procalcitonin	Baseline	0.0530 ng/mL

Secondary

Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test

Virologic markers: conversion to a negative SARS-CoV-2 (qualitative) test on Day 28.

Time frame: on Day 28

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
IMU-838	Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test	57 Participants
Placebo	Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test	60 Participants

Secondary

Temperature

Temperature data at different time point.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Temperature	Baseline	36.9 degrees Celsius	Standard Deviation 0.58
IMU-838	Temperature	Day 6	36.7 degrees Celsius	Standard Deviation 0.33
IMU-838	Temperature	Day 14	36.4 degrees Celsius	Standard Deviation 0.24
IMU-838	Temperature	Day 28	36.4 degrees Celsius	Standard Deviation 0.21
Placebo	Temperature	Day 28	36.4 degrees Celsius	Standard Deviation 0.34
Placebo	Temperature	Baseline	36.8 degrees Celsius	Standard Deviation 0.53
Placebo	Temperature	Day 14	36.4 degrees Celsius	Standard Deviation 0.34
Placebo	Temperature	Day 6	36.5 degrees Celsius	Standard Deviation 0.42

Secondary

Time to Clinical Improvement

Defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the Modified WHO Ordinal Scale for Clinical Status (Modified WHO Ordinal Scale for Clinical Status), or live discharge from hospital without oxygen supplementation, whichever comes first. The 50% Kaplan-Meier quartile (median) of actual values per treatment arm is provided as outcome of this variable below.

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

Arm	Measure	Value (MEDIAN)
IMU-838	Time to Clinical Improvement	13.70 days
Placebo	Time to Clinical Improvement	13.80 days

Secondary

Time to Clinical Recovery

Time of first assessments of parameters contributing to clinical recovery

Time frame: Throughout the Study (Day 0 to EoS [Day 27 up to Day 42])

Population: The first clinical recovery is counted when later relapses are absent. Except for Day 28/early termination/last day with non-missing assessment, only events where clinical recovery is confirmed on the next visit with non-missing assessment(s) are counted. For Day 28/early termination/last day with non-missing assessment this confirmation is not needed. EoS can be \> 28 days as due to COVID-19 restrictions some patients came late (up to Day 42), which was considered a minor protocol deviation.

Arm	Measure	Value (MEDIAN)
IMU-838	Time to Clinical Recovery	14.10 days
Placebo	Time to Clinical Recovery	14.10 days

Secondary

Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test

Virologic markers : Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test Throughout the study. Only patients with viral load measured from nasopharyngeal swab and results provided by the central laboratory (Covance) were included.Conversion to a negative SARS-CoV-2 status is only assumed if a negative test is confirmed by all available subsequent assessments. This means for Day 28/early termination visit no confirmation is needed. If no conversion to a negative status is documented, patients will be censored for survival analysis at the time of the last documented positive test result.

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

Arm	Measure	Value (MEAN)
IMU-838	Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test	13.8 days
Placebo	Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test	14.0 days

Secondary

Troponin I

Bood levels of disease markers

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

Arm	Measure	Group	Value (MEDIAN)
IMU-838	Troponin I	Baseline	0.00860 ug/L
IMU-838	Troponin I	Day 14	0.00860 ug/L
IMU-838	Troponin I	Day 28	0.00860 ug/L
Placebo	Troponin I	Baseline	0.00860 ug/L
Placebo	Troponin I	Day 14	0.00860 ug/L
Placebo	Troponin I	Day 28	0.00860 ug/L

Secondary

Tumor Necrosis Factor Alpha

The profiles of immune system biomarkers

Time frame: Day 0, 6, 14 and 28

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Tumor Necrosis Factor Alpha	Baseline	3.084 ng/L	Standard Deviation 3.314
IMU-838	Tumor Necrosis Factor Alpha	Day 6	6.617 ng/L	Standard Deviation 21.461
IMU-838	Tumor Necrosis Factor Alpha	Day 14	7.974 ng/L	Standard Deviation 18.526
IMU-838	Tumor Necrosis Factor Alpha	Day 28	4.778 ng/L	Standard Deviation 9.293
Placebo	Tumor Necrosis Factor Alpha	Day 28	3.717 ng/L	Standard Deviation 5.69
Placebo	Tumor Necrosis Factor Alpha	Baseline	3.310 ng/L	Standard Deviation 5.071
Placebo	Tumor Necrosis Factor Alpha	Day 14	12.064 ng/L	Standard Deviation 12.064
Placebo	Tumor Necrosis Factor Alpha	Day 6	8.020 ng/L	Standard Deviation 18.418

Secondary

Urine Creatinine at Various Time Points

Clinical laboratory parameters: urinalysis- Urine creatinine at various time points

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

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Urine Creatinine at Various Time Points	Baseline	11368.1 umol/L	Standard Deviation 7672
IMU-838	Urine Creatinine at Various Time Points	Day 6	9259.5 umol/L	Standard Deviation 5198.1
IMU-838	Urine Creatinine at Various Time Points	Day 14	8940.8 umol/L	Standard Deviation 5771
IMU-838	Urine Creatinine at Various Time Points	Day 28	10498.2 umol/L	Standard Deviation 7776.1
Placebo	Urine Creatinine at Various Time Points	Day 28	11589.2 umol/L	Standard Deviation 6665.9
Placebo	Urine Creatinine at Various Time Points	Baseline	11303.9 umol/L	Standard Deviation 6496.6
Placebo	Urine Creatinine at Various Time Points	Day 14	10040.1 umol/L	Standard Deviation 6399.2
Placebo	Urine Creatinine at Various Time Points	Day 6	10214.0 umol/L	Standard Deviation 6551.3

Secondary

Vital Signs: Body Temperature (ºC)

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.

Time frame: at Baseline

Arm	Measure	Value (MEAN)	Dispersion
IMU-838	Vital Signs: Body Temperature (ºC)	36.86 degrees Celsius	Standard Deviation 0.58
Placebo	Vital Signs: Body Temperature (ºC)	36.75 degrees Celsius	Standard Deviation 0.53

Secondary

Vital Signs: Height

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.

Time frame: at Baseline

Population: For 55 female and 55 male in group IMU-838 and 46 female and 64 male in Placebo group

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Vital Signs: Height	Male	178.1 centimeters	Standard Deviation 5.7
IMU-838	Vital Signs: Height	Female	163.0 centimeters	Standard Deviation 5.5
Placebo	Vital Signs: Height	Male	175.6 centimeters	Standard Deviation 6.8
Placebo	Vital Signs: Height	Female	163.9 centimeters	Standard Deviation 4.4

Secondary

Vital Signs: Weight

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.

Time frame: at Baseline

Population: For 55 female and 55 male in group IMU-838 and 46 female and 64 male in Placebo group.

Arm	Measure	Group	Value (MEAN)	Dispersion
IMU-838	Vital Signs: Weight	Male	92.98 kilograms	Standard Deviation 18.86
IMU-838	Vital Signs: Weight	Female	77.88 kilograms	Standard Deviation 14.46
Placebo	Vital Signs: Weight	Male	88.95 kilograms	Standard Deviation 14.05
Placebo	Vital Signs: Weight	Female	74.09 kilograms	Standard Deviation 13.89

Source: ClinicalTrials.gov · Data processed: Feb 17, 2026

A Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19 (COVID-19)

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Masking description

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Proportion of Patients Without Any Need for INV Until EoS

Albumin Concentration at Various Time Points

All Cause Mortality (ITT Approach)

Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points

Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6

Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes

C-reactive Protein

Cumulative Dose

Days in ICU Department

Days of Auxiliary Oxygen Therapy

Days of Hospitalization

Days of Hospitalization

Days on ECMO

Days on RRT

Days to ECMO

Days to INV

Days to INV, RRT and ECMO

Days to RRT

D-dimer

Duration of INV

Hematocrit Ratio at Various Time Points

Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2

Interferon Gamma (IFNγ)

Interleukin (IL)-17

Interleukin (IL)-1ß

Interleukin (IL)-6

Lactate Dehydrogenase (LDH)

Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples

Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart

Number of Participants With Adverse Events (AEs) and Serious AEs

Number of Patients Free of ECMO

Participants With ICU Admission

Patients Free of INV Until Day 14*

Patients Free of Renal-replacement Therapy (RRT)* Until EoS

Patients Free of RRT

Patients Required ECMO Until EoS

Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)

Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation

Patients With Clinical Recovery

Patients With Clinical Recovery

Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1

Percentage of Participants With WHO Status<=2

Plasma Levels of IMU-838

Probability of Death

Probability of ICU Admission

Procalcitonin

Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test

Temperature

Time to Clinical Improvement

Time to Clinical Recovery

Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test

Troponin I

Tumor Necrosis Factor Alpha

Urine Creatinine at Various Time Points

Vital Signs: Body Temperature (ºC)

Vital Signs: Height

Vital Signs: Weight