Trial Outcomes & Findings for 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) (NCT NCT04379271)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

234 participants

Primary outcome timeframe

Throughout the Study (Day 0 to Day 28)

Results posted on

2024-11-13

Participant Flow

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).

Participant milestones

Participant milestones
Measure	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.	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
Overall Study STARTED	110	110
Overall Study COMPLETED	93	97
Overall Study NOT COMPLETED	17	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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	Total n=220 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	83 Participants n=5 Participants	83 Participants n=7 Participants	166 Participants n=5 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Age, Continuous	54.5 years STANDARD_DEVIATION 13.4 • n=5 Participants	53.7 years STANDARD_DEVIATION 14.2 • n=7 Participants	54.1 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	46 Participants n=7 Participants	101 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	64 Participants n=7 Participants	119 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	110 Participants n=5 Participants	107 Participants n=7 Participants	217 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

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

Population: FAS, Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Proportion of Patients Without Any Need for INV Until EoS No INV needed	98 Participants	101 Participants
Proportion of Patients Without Any Need for INV Until EoS INV needed	12 Participants	9 Participants

SECONDARY outcome

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

Population: FAS

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

Outcome measures

Outcome measures
Measure	IMU-838 n=4 Participants 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.	Placebo n=5 Participants 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
Days in ICU Department	2.54 days Standard Deviation 7.24	2.33 days Standard Deviation 7.24

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
All Cause Mortality (ITT Approach) actual death	2 Participants	2 Participants
All Cause Mortality (ITT Approach) 28 days all cause mortality (including lost to follow-up)	9 Participants	8 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Time to Clinical Improvement	13.70 days Interval 13.7 to 13.8	13.80 days Interval 13.7 to 13.8

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=73 Participants 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.	Placebo n=77 Participants 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
Days of Hospitalization	13.49 days Standard Deviation 7.00	14.35 days Standard Deviation 7.71

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Patients Free of Renal-replacement Therapy (RRT)* Until EoS	110 Participants	110 Participants

SECONDARY outcome

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

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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Patients Required ECMO Until EoS	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	IMU-838 n=103 Participants 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.	Placebo n=100 Participants 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
Patients Free of INV Until Day 14*	102 Participants	99 Participants

SECONDARY outcome

Timeframe: Day 0 to Day 14

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

Percentage of patients free of RRT until Day 14\*

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Patients Free of RRT	110 Participants	110 Participants

SECONDARY outcome

Timeframe: 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.

Number of patients free of ECMO until Day 14.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Number of Patients Free of ECMO	110 Participants	110 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1 Day 6	5 participants	5 participants
Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1 Day 14	44 participants	39 participants
Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1 Day 28	95 participants	93 participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=108 Participants 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.	Placebo n=108 Participants 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
Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy) Day 6	47.2 percentage of participants	40.7 percentage of participants
Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy) Day 14	47.7 percentage of participants	41.1 percentage of participants
Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy) Day 28	48.1 percentage of participants	42.1 percentage of participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=109 Participants 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.	Placebo n=110 Participants 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
Patients With Clinical Recovery Baseline	3.7 percent of patients	3.6 percent of patients
Patients With Clinical Recovery Day 0	5.5 percent of patients	3.7 percent of patients
Patients With Clinical Recovery Day 7	17.4 percent of patients	12.0 percent of patients
Patients With Clinical Recovery Day 10	21.7 percent of patients	19.5 percent of patients
Patients With Clinical Recovery Day 14	40.2 percent of patients	45.8 percent of patients
Patients With Clinical Recovery Day 28	69.3 percent of patients	65.6 percent of patients

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	IMU-838 n=103 Participants 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.	Placebo n=103 Participants 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
Patients With Clinical Recovery Day 14	40.2 percent of patients	45.8 percent of patients
Patients With Clinical Recovery Day 28	69.3 percent of patients	65.6 percent of patients
Patients With Clinical Recovery Day 7	17.4 percent of patients	12.0 percent of patients

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Outcome measures
Measure	IMU-838 n=109 Participants 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.	Placebo n=110 Participants 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
Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation	91.7 percent of patients	88.2 percent of patients

SECONDARY outcome

Timeframe: on Days 6, 14, and 28

Population: Missing data

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Percentage of Participants With WHO Status<=2 Day 6	6.3 percentage of patients, WHO status <=2	5.1 percentage of patients, WHO status <=2
Percentage of Participants With WHO Status<=2 Day 14	48.5 percentage of patients, WHO status <=2	44.3 percentage of patients, WHO status <=2
Percentage of Participants With WHO Status<=2 Day 28	97.9 percentage of patients, WHO status <=2	96.9 percentage of patients, WHO status <=2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=99 Participants 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.	Placebo n=100 Participants 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
Duration of INV	0.00 days Interval 0.0 to 0.1	0.07 days Interval 0.0 to 7.0

SECONDARY outcome

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

Population: patients, who require ECMO throughout the study

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Days on ECMO	0 days	0 days

SECONDARY outcome

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

Population: patients , who require RRT throughout the study

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Days on RRT	0 days	0 days

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=51 Participants 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.	Placebo n=45 Participants 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
Days of Auxiliary Oxygen Therapy	4.49 days Standard Deviation 7.01	3.86 days Standard Deviation 7.26

SECONDARY outcome

Timeframe: 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

Duration of hospitalization for survivors

Outcome measures

Outcome measures
Measure	IMU-838 n=71 Participants 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.	Placebo n=75 Participants 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
Days of Hospitalization	13.53 days Interval 6.9 to 15.9	14.52 days Interval 7.3 to 19.0

SECONDARY outcome

Timeframe: on Days 6, 14, and 28

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

Percentage of Participants with ICU Admission at different time point

Outcome measures

Outcome measures
Measure	IMU-838 n=107 Participants 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.	Placebo n=105 Participants 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
Participants With ICU Admission Day 6	3.7 percent of patients	3.8 percent of patients
Participants With ICU Admission Day 14	3.8 percent of patients	5.0 percent of patients
Participants With ICU Admission Day 28	4.0 percent of patients	5.0 percent of patients

SECONDARY outcome

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

Probability of death derived from Kaplan Meier analyses

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Probability of Death	0.019 Probability	0.019 Probability

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=1 Participants 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.	Placebo n=1 Participants 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
Days to INV	13.8 days Interval 13.8 to 13.8	6.0 days Interval 6.0 to 6.0

SECONDARY outcome

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

Population: No patients required RRT during the trial

Time to first prescription of RRT

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: No patients required ECMO during the trial

Time to first prescription of ECMO

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=1 Participants 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.	Placebo n=1 Participants 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
Days to INV, RRT and ECMO	13.8 days Interval 13.8 to 13.8	6.0 days Interval 6.0 to 6.0

SECONDARY outcome

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

Overall probability of ICU admission derived from Kaplan Meier analyses.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Probability of ICU Admission	0.037 Probability	0.047 Probability

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=1 Participants 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.	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
Cumulative Dose	0 mg	—

SECONDARY outcome

Timeframe: 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.

Time of first assessments of parameters contributing to clinical recovery

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Time to Clinical Recovery	14.10 days Interval 12.9 to 27.8	14.10 days Interval 13.7 to 27.9

SECONDARY outcome

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

Population: Placebo group not available

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	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
Plasma Levels of IMU-838 Baseline	0.1108 ug/mL Standard Deviation 0.1135	—
Plasma Levels of IMU-838 Day 1	2.9234 ug/mL Standard Deviation 1.1493	—
Plasma Levels of IMU-838 Day 2	3.5724 ug/mL Standard Deviation 1.6299	—
Plasma Levels of IMU-838 Day 3	3.8572 ug/mL Standard Deviation 1.8606	—
Plasma Levels of IMU-838 Day 6	4.3607 ug/mL Standard Deviation 2.4872	—
Plasma Levels of IMU-838 Day 14	4.6514 ug/mL Standard Deviation 2.6506	—
Plasma Levels of IMU-838 Day 28	0.1014 ug/mL Standard Deviation 0.0093	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=94 Participants 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.	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
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 Interval 13.2 to 29.1	—
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 Interval 12.9 to 28.8	—
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 Interval 6.0 to 13.7	—
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 Interval 4.8 to 14.1	—
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 Interval 13.7 to 14.0	—
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 Interval 13.7 to 14.8	—
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 Interval 13.1 to 13.8	—
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 Interval 11.0 to 13.9	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Number of Participants With Adverse Events (AEs) and Serious AEs Any AE	81 Participants	69 Participants
Number of Participants With Adverse Events (AEs) and Serious AEs Any serious AE	2 Participants	4 Participants

SECONDARY outcome

Timeframe: at Baseline

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

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Vital Signs: Height Male	178.1 centimeters Standard Deviation 5.7	175.6 centimeters Standard Deviation 6.8
Vital Signs: Height Female	163.0 centimeters Standard Deviation 5.5	163.9 centimeters Standard Deviation 4.4

SECONDARY outcome

Timeframe: at Baseline

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

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Vital Signs: Weight Male	92.98 kilograms Standard Deviation 18.86	88.95 kilograms Standard Deviation 14.05
Vital Signs: Weight Female	77.88 kilograms Standard Deviation 14.46	74.09 kilograms Standard Deviation 13.89

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IMU-838 n=108 Participants 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.	Placebo n=109 Participants 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
Vital Signs: Body Temperature (ºC)	36.86 degrees Celsius Standard Deviation 0.58	36.75 degrees Celsius Standard Deviation 0.53

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=108 Participants 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
Albumin Concentration at Various Time Points Baseline	39.4 g/L Standard Deviation 4.4	40.2 g/L Standard Deviation 4.7
Albumin Concentration at Various Time Points Day 6	37.9 g/L Standard Deviation 4.2	38.7 g/L Standard Deviation 4.9
Albumin Concentration at Various Time Points Day 14	39.6 g/L Standard Deviation 4.6	40.3 g/L Standard Deviation 4.6
Albumin Concentration at Various Time Points Day 28	44.0 g/L Standard Deviation 3.7	44.0 g/L Standard Deviation 4.4

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	IMU-838 n=108 Participants 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.	Placebo n=106 Participants 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
Hematocrit Ratio at Various Time Points Baseline	0.435 ratio Standard Deviation 0.052	0.448 ratio Standard Deviation 0.053
Hematocrit Ratio at Various Time Points Day 6	0.430 ratio Standard Deviation 0.059	0.443 ratio Standard Deviation 0.053
Hematocrit Ratio at Various Time Points Day 14	0.435 ratio Standard Deviation 0.049	0.440 ratio Standard Deviation 0.051
Hematocrit Ratio at Various Time Points Day 28	0.428 ratio Standard Deviation 0.046	0.432 ratio Standard Deviation 0.052

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	IMU-838 n=109 Participants 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.	Placebo n=107 Participants 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
Urine Creatinine at Various Time Points Baseline	11368.1 umol/L Standard Deviation 7672.0	11303.9 umol/L Standard Deviation 6496.6
Urine Creatinine at Various Time Points Day 6	9259.5 umol/L Standard Deviation 5198.1	10214.0 umol/L Standard Deviation 6551.3
Urine Creatinine at Various Time Points Day 14	8940.8 umol/L Standard Deviation 5771.0	10040.1 umol/L Standard Deviation 6399.2
Urine Creatinine at Various Time Points Day 28	10498.2 umol/L Standard Deviation 7776.1	11589.2 umol/L Standard Deviation 6665.9

SECONDARY outcome

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

Temperature data at different time point.

Outcome measures

Outcome measures
Measure	IMU-838 n=108 Participants 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.	Placebo n=109 Participants 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
Temperature Baseline	36.9 degrees Celsius Standard Deviation 0.58	36.8 degrees Celsius Standard Deviation 0.53
Temperature Day 6	36.7 degrees Celsius Standard Deviation 0.33	36.5 degrees Celsius Standard Deviation 0.42
Temperature Day 14	36.4 degrees Celsius Standard Deviation 0.24	36.4 degrees Celsius Standard Deviation 0.34
Temperature Day 28	36.4 degrees Celsius Standard Deviation 0.21	36.4 degrees Celsius Standard Deviation 0.34

SECONDARY outcome

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

Disease markers

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=109 Participants 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
D-dimer Day 28	343.0 ng/mL Interval 100.0 to 19520.0	332.5 ng/mL Interval 76.0 to 9076.0
D-dimer Baseline	529.5 ng/mL Interval 79.0 to 19520.0	473.0 ng/mL Interval 106.0 to 5647.0
D-dimer Day 14	348.0 ng/mL Interval 91.0 to 19520.0	357.0 ng/mL Interval 60.0 to 19520.0

SECONDARY outcome

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

Blood levels of disease markers

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Lactate Dehydrogenase (LDH) Baseline	4176.0 nkat/L Interval 1900.0 to 14886.0	4059.0 nkat/L Interval 1900.0 to 14886.0
Lactate Dehydrogenase (LDH) Day 14	3167.0 nkat/L Interval 1650.0 to 11302.0	3117.0 nkat/L Interval 1850.0 to 10752.0
Lactate Dehydrogenase (LDH) Day 28	3375.5 nkat/L Interval 1650.0 to 7918.0	3267.0 nkat/L Interval 1650.0 to 15053.0

SECONDARY outcome

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

Blood levels of disease markers

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
C-reactive Protein Baseline	320.4826 nmol/L Interval 5.7144 to 2682.911	245.2430 nmol/L Interval 5.7144 to 2362.904
C-reactive Protein Day 14	27.61960 nmol/L Interval 5.7144 to 6328.698	20.95280 nmol/L Interval 5.7144 to 858.1124
C-reactive Protein Day 28	23.81000 nmol/L Interval 5.7144 to 207.6232	16.19080 nmol/L Interval 5.7144 to 1447.648

SECONDARY outcome

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

Bood levels of disease markers

Outcome measures

Outcome measures
Measure	IMU-838 n=103 Participants 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.	Placebo n=97 Participants 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
Troponin I Baseline	0.00860 ug/L Interval 0.0086 to 0.0904	0.00860 ug/L Interval 0.0086 to 0.1054
Troponin I Day 14	0.00860 ug/L Interval 0.0086 to 0.0812	0.00860 ug/L Interval 0.0086 to 1.0152
Troponin I Day 28	0.00860 ug/L Interval 0.0086 to 0.0542	0.00860 ug/L Interval 0.0086 to 0.1053

SECONDARY outcome

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

Blood levels of disease markers

Outcome measures

Outcome measures
Measure	IMU-838 n=108 Participants 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.	Placebo n=107 Participants 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
Procalcitonin Baseline	0.0695 ng/mL Interval 0.02 to 0.513	0.0530 ng/mL Interval 0.02 to 0.568
Procalcitonin Day 14	0.0410 ng/mL Interval 0.02 to 2.88	0.0340 ng/mL Interval 0.02 to 0.12
Procalcitonin Day 28	0.0380 ng/mL Interval 0.02 to 0.246	0.0350 ng/mL Interval 0.02 to 1.84

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IMU-838 n=100 Participants 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.	Placebo n=101 Participants 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
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 Interval 13.7 to 14.8	13.8 days Interval 13.0 to 14.8
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 Interval 7.6 to 14.8	13.8 days Interval 13.7 to 13.8
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 Interval 12.0 to 13.9	13.8 days Interval 10.8 to 15.8
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 Interval 12.0 to 14.0	13.8 days Interval 13.7 to 14.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	IMU-838 n=67 Participants 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.	Placebo n=72 Participants 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
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	-62534293.5 Change in log10 copies Standard Deviation 380490492.5
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	-84355538.5 Change in log10 copies Standard Deviation 416667915.1
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	-89534493.9 Change in log10 copies Standard Deviation 429884542.5
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	-44774028.6 Change in log10 copies Standard Deviation 249373454.1

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	IMU-838 n=78 Participants 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.	Placebo n=77 Participants 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
Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples Day 14	37642.6 log10 Copies Standard Deviation 281630.2	483522.2 log10 Copies Standard Deviation 3851254.5
Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples Baseline	10966569.9 log10 Copies Standard Deviation 46215130.5	75572844.7 log10 Copies Standard Deviation 389541813.1
Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples Day 6	33277.7 log10 Copies Standard Deviation 168585.9	581813.6 log10 Copies Standard Deviation 3313425.6
Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples Day 28	181.6 log10 Copies Standard Deviation 673.9	369.7 log10 Copies Standard Deviation 2133.1

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart	69 Participants	77 Participants

SECONDARY outcome

Timeframe: on Day 28

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

Outcome measures

Outcome measures
Measure	IMU-838 n=100 Participants 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.	Placebo n=98 Participants 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
Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test	57 Participants	60 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IMU-838 n=100 Participants 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.	Placebo n=98 Participants 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
Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test	13.8 days Interval 12.8 to 14.1	14.0 days Interval 13.7 to 27.8

SECONDARY outcome

Timeframe: Day 0, 6, 14 and Day 28

The profiles of immune system biomarkers

Outcome measures

Outcome measures
Measure	IMU-838 n=106 Participants 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.	Placebo n=107 Participants 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
Interleukin (IL)-17 Baseline	5.860 pg/mL Standard Deviation 0.000	5.860 pg/mL Standard Deviation 0.000
Interleukin (IL)-17 Day 6	5.860 pg/mL Standard Deviation 0.000	5.885 pg/mL Standard Deviation 0.177
Interleukin (IL)-17 Day 14	5.924 pg/mL Standard Deviation 0.621	5.860 pg/mL Standard Deviation 0.000
Interleukin (IL)-17 Day 28	5.866 pg/mL Standard Deviation 0.058	5.892 pg/mL Standard Deviation 0.308

SECONDARY outcome

Timeframe: Day 0, 6, 14 and Day 28

The profiles of immune system biomarkers

Outcome measures

Outcome measures
Measure	IMU-838 n=106 Participants 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.	Placebo n=107 Participants 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
Interleukin (IL)-1ß Baseline	0.668 ng/L Standard Deviation 0.159	0.654 ng/L Standard Deviation 0.032
Interleukin (IL)-1ß Day 6	1.014 ng/L Standard Deviation 1.865	1.100 ng/L Standard Deviation 2.165
Interleukin (IL)-1ß Day 14	0.976 ng/L Standard Deviation 1.955	0.862 ng/L Standard Deviation 0.970
Interleukin (IL)-1ß Day 28	0.984 ng/L Standard Deviation 2.240	0.662 ng/L Standard Deviation 0.076

SECONDARY outcome

Timeframe: Day 0, 6, 14 and 28

The profiles of immune system biomarkers

Outcome measures

Outcome measures
Measure	IMU-838 n=106 Participants 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.	Placebo n=107 Participants 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
Interleukin (IL)-6 Baseline	6.217 ng/L Standard Deviation 8.037	5.093 ng/L Standard Deviation 6.438
Interleukin (IL)-6 Day 6	5.441 ng/L Standard Deviation 14.271	8.435 ng/L Standard Deviation 30.854
Interleukin (IL)-6 Day 14	7.697 ng/L Standard Deviation 25.514	5.536 ng/L Standard Deviation 26.081
Interleukin (IL)-6 Day 28	3.437 ng/L Standard Deviation 14.317	1.468 ng/L Standard Deviation 1.879

SECONDARY outcome

Timeframe: Day 0, 6, 14 and 28

The profiles of immune system biomarkers

Outcome measures

Outcome measures
Measure	IMU-838 n=106 Participants 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.	Placebo n=107 Participants 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
Interferon Gamma (IFNγ) Day 14	10.469 pg/mL Standard Deviation 13.224	38.192 pg/mL Standard Deviation 150.623
Interferon Gamma (IFNγ) Day 28	17.013 pg/mL Standard Deviation 33.762	14.452 pg/mL Standard Deviation 21.067
Interferon Gamma (IFNγ) Baseline	94.364 pg/mL Standard Deviation 166.465	92.190 pg/mL Standard Deviation 153.798
Interferon Gamma (IFNγ) Day 6	28.654 pg/mL Standard Deviation 90.127	24.141 pg/mL Standard Deviation 77.850

SECONDARY outcome

Timeframe: Day 0, 6, 14 and 28

The profiles of immune system biomarkers

Outcome measures

Outcome measures
Measure	IMU-838 n=106 Participants 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.	Placebo n=107 Participants 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
Tumor Necrosis Factor Alpha Baseline	3.084 ng/L Standard Deviation 3.314	3.310 ng/L Standard Deviation 5.071
Tumor Necrosis Factor Alpha Day 6	6.617 ng/L Standard Deviation 21.461	8.020 ng/L Standard Deviation 18.418
Tumor Necrosis Factor Alpha Day 14	7.974 ng/L Standard Deviation 18.526	12.064 ng/L Standard Deviation 12.064
Tumor Necrosis Factor Alpha Day 28	4.778 ng/L Standard Deviation 9.293	3.717 ng/L Standard Deviation 5.690

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	IMU-838 n=110 Participants 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.	Placebo n=110 Participants 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
Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2 Day 6	86.0 percent of patients	83.8 percent of patients
Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2 Day 14	96.9 percent of patients	94.3 percent of patients
Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2 Day 28	98.3 percent of patients	96.9 percent of patients

Adverse Events

IMU-838

Serious events: 2 serious events

Other events: 79 other events

Deaths: 2 deaths

Placebo

Serious events: 4 serious events

Other events: 65 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	IMU-838 n=110 participants at risk 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.	Placebo n=110 participants at risk 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
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/110 • Adverse event data were collected until Day 60 after randomization	0.91% 1/110 • Adverse event data were collected until Day 60 after randomization
Vascular disorders Thrombosis	0.00% 0/110 • Adverse event data were collected until Day 60 after randomization	0.91% 1/110 • Adverse event data were collected until Day 60 after randomization
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/110 • Adverse event data were collected until Day 60 after randomization	0.91% 1/110 • Adverse event data were collected until Day 60 after randomization
Investigations Death	1.8% 2/110 • Adverse event data were collected until Day 60 after randomization	1.8% 2/110 • Adverse event data were collected until Day 60 after randomization

Other adverse events

Other adverse events
Measure	IMU-838 n=110 participants at risk 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.	Placebo n=110 participants at risk 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
Blood and lymphatic system disorders Anaemia	3.6% 4/110 • Number of events 4 • Adverse event data were collected until Day 60 after randomization	5.5% 6/110 • Number of events 6 • Adverse event data were collected until Day 60 after randomization
Cardiac disorders Bradycardia	3.6% 4/110 • Number of events 6 • Adverse event data were collected until Day 60 after randomization	6.4% 7/110 • Number of events 10 • Adverse event data were collected until Day 60 after randomization
Cardiac disorders Sinus bradycardia	5.5% 6/110 • Number of events 6 • Adverse event data were collected until Day 60 after randomization	4.5% 5/110 • Number of events 5 • Adverse event data were collected until Day 60 after randomization
Cardiac disorders Tachycardia	6.4% 7/110 • Number of events 7 • Adverse event data were collected until Day 60 after randomization	1.8% 2/110 • Number of events 2 • Adverse event data were collected until Day 60 after randomization
Hepatobiliary disorders Hepatocellular injury	2.7% 3/110 • Number of events 4 • Adverse event data were collected until Day 60 after randomization	6.4% 7/110 • Number of events 7 • Adverse event data were collected until Day 60 after randomization
Investigations Alanine aminotransferase increased	4.5% 5/110 • Number of events 5 • Adverse event data were collected until Day 60 after randomization	5.5% 6/110 • Number of events 6 • Adverse event data were collected until Day 60 after randomization
Investigations Glycosylated haemoglobin increased	9.1% 10/110 • Number of events 10 • Adverse event data were collected until Day 60 after randomization	5.5% 6/110 • Number of events 6 • Adverse event data were collected until Day 60 after randomization
Metabolism and nutrition disorders Hyperglycaemia	4.5% 5/110 • Number of events 7 • Adverse event data were collected until Day 60 after randomization	7.3% 8/110 • Number of events 8 • Adverse event data were collected until Day 60 after randomization
Metabolism and nutrition disorders Hypertriglyceridaemia	20.9% 23/110 • Number of events 24 • Adverse event data were collected until Day 60 after randomization	11.8% 13/110 • Number of events 13 • Adverse event data were collected until Day 60 after randomization
Nervous system disorders Headache	7.3% 8/110 • Number of events 9 • Adverse event data were collected until Day 60 after randomization	4.5% 5/110 • Number of events 6 • Adverse event data were collected until Day 60 after randomization
Renal and urinary disorders Haematuria	6.4% 7/110 • Number of events 7 • Adverse event data were collected until Day 60 after randomization	3.6% 4/110 • Number of events 4 • Adverse event data were collected until Day 60 after randomization
Vascular disorders Hypertension	5.5% 6/110 • Number of events 8 • Adverse event data were collected until Day 60 after randomization	3.6% 4/110 • Number of events 8 • Adverse event data were collected until Day 60 after randomization
Vascular disorders Hypertensive crisis	5.5% 6/110 • Number of events 8 • Adverse event data were collected until Day 60 after randomization	2.7% 3/110 • Number of events 3 • Adverse event data were collected until Day 60 after randomization

Additional Information

Silke Kropp, Specialist Regulatory Operations & Systems

Immunic AG

Phone: +49

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place