Trial Outcomes & Findings for Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia (NCT NCT04467840)

Last Updated: 2025-07-31

Results Overview

To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

475 participants

Primary outcome timeframe

14 days maintained up to 42 days

Results posted on

2025-07-31

Participant Flow

Participant milestones

Participant milestones
Measure	Opaganib In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Overall Study STARTED	237	238
Overall Study mITT Population	230	233
Overall Study COMPLETED	186	186
Overall Study NOT COMPLETED	51	52

Reasons for withdrawal

Reasons for withdrawal
Measure	Opaganib In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Overall Study Death	35	39
Overall Study Withdrawal by Subject	8	4
Overall Study Adverse Event	2	0
Overall Study Lost to Follow-up	1	3
Overall Study Physician Decision	1	0
Overall Study Other	1	5
Overall Study Missing study completion status	3	1

Baseline Characteristics

Information reported according to data collected. Where the number of participants analyzed differs from the overall, the data was not collected/reported by the clinical site.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Opaganib n=237 Participants Opaganib administered orally in 2 x 250 mg capsules (500 mg) every 12 hours every day for 14 days (Day 1 to Day 14) in addition to standard of care. When required this may be made into a suspension form and may be administered by nasogastric tube.	Placebo n=238 Participants Matching placebo administered orally in 2 x 250 mg capsules (500 mg) every 12 hours every day for 14 days (Day 1 to Day 14) in addition to standard of care. Where required this may be made into a suspension form and may be administered by nasogastric tube.	Total n=475 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=237 Participants	0 Participants n=238 Participants	0 Participants n=475 Participants
Age, Categorical Between 18 and 65 years	189 Participants n=237 Participants	169 Participants n=238 Participants	358 Participants n=475 Participants
Age, Categorical >=65 years	48 Participants n=237 Participants	69 Participants n=238 Participants	117 Participants n=475 Participants
Age, Continuous	55.6 Years STANDARD_DEVIATION 12.05 • n=237 Participants	57.3 Years STANDARD_DEVIATION 12.74 • n=238 Participants	56.5 Years STANDARD_DEVIATION 12.42 • n=475 Participants
Sex: Female, Male Female	86 Participants n=237 Participants	76 Participants n=238 Participants	162 Participants n=475 Participants
Sex: Female, Male Male	151 Participants n=237 Participants	162 Participants n=238 Participants	313 Participants n=475 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=237 Participants	4 Participants n=238 Participants	9 Participants n=475 Participants
Race (NIH/OMB) Asian	1 Participants n=237 Participants	0 Participants n=238 Participants	1 Participants n=475 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=237 Participants	0 Participants n=238 Participants	0 Participants n=475 Participants
Race (NIH/OMB) Black or African American	10 Participants n=237 Participants	10 Participants n=238 Participants	20 Participants n=475 Participants
Race (NIH/OMB) White	197 Participants n=237 Participants	203 Participants n=238 Participants	400 Participants n=475 Participants
Race (NIH/OMB) More than one race	1 Participants n=237 Participants	3 Participants n=238 Participants	4 Participants n=475 Participants
Race (NIH/OMB) Unknown or Not Reported	23 Participants n=237 Participants	18 Participants n=238 Participants	41 Participants n=475 Participants
Region of Enrollment Colombia	10 participants n=237 Participants	8 participants n=238 Participants	18 participants n=475 Participants
Region of Enrollment Brazil	61 participants n=237 Participants	62 participants n=238 Participants	123 participants n=475 Participants
Region of Enrollment Poland	12 participants n=237 Participants	16 participants n=238 Participants	28 participants n=475 Participants
Region of Enrollment Italy	25 participants n=237 Participants	28 participants n=238 Participants	53 participants n=475 Participants
Region of Enrollment Mexico	7 participants n=237 Participants	4 participants n=238 Participants	11 participants n=475 Participants
Region of Enrollment Israel	43 participants n=237 Participants	40 participants n=238 Participants	83 participants n=475 Participants
Region of Enrollment Russia	79 participants n=237 Participants	80 participants n=238 Participants	159 participants n=475 Participants
HbA1c at Screening <6.5 and not on active treatment with insulin or oral hypoglycemics	154 Participants n=237 Participants	157 Participants n=238 Participants	311 Participants n=475 Participants
HbA1c at Screening ≥6.5 or on active treatment with insulin or oral hypoglycemics	83 Participants n=237 Participants	80 Participants n=238 Participants	163 Participants n=475 Participants
HbA1c at Screening Missing	0 Participants n=237 Participants	1 Participants n=238 Participants	1 Participants n=475 Participants
BMI at Baseline (kg/m^2)	31.02 kg/m2 STANDARD_DEVIATION 5.676 • n=223 Participants • Information reported according to data collected. Where the number of participants analyzed differs from the overall, the data was not collected/reported by the clinical site.	30.47 kg/m2 STANDARD_DEVIATION 5.158 • n=228 Participants • Information reported according to data collected. Where the number of participants analyzed differs from the overall, the data was not collected/reported by the clinical site.	30.74 kg/m2 STANDARD_DEVIATION 5.421 • n=451 Participants • Information reported according to data collected. Where the number of participants analyzed differs from the overall, the data was not collected/reported by the clinical site.
Supplemental Oxygen at Baseline Yes	229 Participants n=237 Participants	233 Participants n=238 Participants	462 Participants n=475 Participants
Supplemental Oxygen at Baseline No	1 Participants n=237 Participants	0 Participants n=238 Participants	1 Participants n=475 Participants
Supplemental Oxygen at Baseline Missing	7 Participants n=237 Participants	5 Participants n=238 Participants	12 Participants n=475 Participants
Oxygen type (for supplemental oxygen at baseline - Yes) Intubation/Mechanical ventilation	1 Participants n=229 Participants • Number of subjects on supplemental oxygen at baseline	2 Participants n=233 Participants • Number of subjects on supplemental oxygen at baseline	3 Participants n=462 Participants • Number of subjects on supplemental oxygen at baseline
Oxygen type (for supplemental oxygen at baseline - Yes) Low Flow Nasal Cannulas (LFNC)	3 Participants n=229 Participants • Number of subjects on supplemental oxygen at baseline	1 Participants n=233 Participants • Number of subjects on supplemental oxygen at baseline	4 Participants n=462 Participants • Number of subjects on supplemental oxygen at baseline
Oxygen type (for supplemental oxygen at baseline - Yes) Non-invasive ventilation/High Flow Nasal Cannulas (HFNC)/Mask with reservoir/Mask without reservoir	225 Participants n=229 Participants • Number of subjects on supplemental oxygen at baseline	230 Participants n=233 Participants • Number of subjects on supplemental oxygen at baseline	455 Participants n=462 Participants • Number of subjects on supplemental oxygen at baseline
Oxygen flow at baseline (L/min)	24.6 L/min STANDARD_DEVIATION 19.59 • n=222 Participants • Baseline oxygen flow was only collected in subjects not intubated at baseline who required oxygen and who had baseline oxygen recorded.	24.9 L/min STANDARD_DEVIATION 19.83 • n=219 Participants • Baseline oxygen flow was only collected in subjects not intubated at baseline who required oxygen and who had baseline oxygen recorded.	24.8 L/min STANDARD_DEVIATION 19.69 • n=441 Participants • Baseline oxygen flow was only collected in subjects not intubated at baseline who required oxygen and who had baseline oxygen recorded.
Oxygen in the gas mix (%)	65.5 Percentage of oxygen STANDARD_DEVIATION 60.0 • n=222 Participants • Missing data was not collected by the clinical sites	64.1 Percentage of oxygen STANDARD_DEVIATION 60.0 • n=222 Participants • Missing data was not collected by the clinical sites	64.8 Percentage of oxygen STANDARD_DEVIATION 60.0 • n=444 Participants • Missing data was not collected by the clinical sites
Median percentage of oxygen in the gas mix (%)	60.0 Percentage of oxygen n=222 Participants • Missing data was not collected by the clinical sites	60.0 Percentage of oxygen n=222 Participants • Missing data was not collected by the clinical sites	60.0 Percentage of oxygen n=444 Participants • Missing data was not collected by the clinical sites
FiO2≤60% sub-population inflammation markers: lymphocyte counts	0.910 10^9*cell/L n=116 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	1.010 10^9*cell/L n=133 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	0.990 10^9*cell/L n=249 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2≤60% sub-population inflammation markers: CRP Levels	67.100 mg/L n=113 Participants • Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	45.00 mg/L n=127 Participants • Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	60.80 mg/L n=240 Participants • Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2≤60% sub-population inflammation markers: Ferritin Levels	727.600 ug/L n=104 Participants • Measure Analysis Population Description: Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	592.300 ug/L n=124 Participants • Measure Analysis Population Description: Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	666.950 ug/L n=228 Participants • Measure Analysis Population Description: Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2≤60% sub-population inflammation markers: D-Dimer Levels	0.499 ug/ml n=111 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed Missing data was not collected by the clinical sites	0.380 ug/ml n=129 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed Missing data was not collected by the clinical sites	0.450 ug/ml n=240 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed Missing data was not collected by the clinical sites
FiO2≤60% sub-population inflammation markers: Lactate Dehydrogenase	359.400 IU/L n=106 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	368.750 IU/L n=124 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	361.150 IU/L n=230 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2>60% sub-population lymphocyte counts	0.840 10^9*cell/L n=105 Participants • Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed.	0.700 10^9*cell/L n=84 Participants • Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed.	0.792 10^9*cell/L n=189 Participants • Measure Analysis Population Description: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed.
FiO2>60% sub-population inflammation markers: CRP levels	94.050 mg/L n=100 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	106.370 mg/L n=86 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	102.800 mg/L n=186 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2>60% sub-population inflammation markers: Ferritin Levels	1074.150 ug/L n=88 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	980.00 ug/L n=79 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	1000.00 ug/L n=167 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2>60% sub-population inflammation markers: D-Dimer Levels	0.790 ug/ml n=94 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	0.836 ug/ml n=84 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	0.806 ug/ml n=178 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites
FiO2>60% sub-population inflammation markers: Lactate Dehydrogenase Levels	477.500 IU/L n=100 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	447.00 IU/L n=83 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites	469.230 IU/L n=183 Participants • A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed. Missing data was not collected by the clinical sites

PRIMARY outcome

Timeframe: 14 days maintained up to 42 days

Population: Modified ITT (mITT) population defined as randomized subjects who received at least one dose of study medication

To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Supplemental Oxygen Requirement Subjects not receiving supplemental oxygen for at least 24 hours by Day 14 and maintained at Day 42	139 Participants	132 Participants
Supplemental Oxygen Requirement Subjects receiving supplemental oxygen (including: death, lost to follow-up, or need of oxygen)	91 Participants	101 Participants

SECONDARY outcome

Timeframe: 14 days maintained up to 42 days

Population: mITT

Compare ≥2 category improvement on the WHO Ordinal Scale for Clinical Improvement from 0(uninfected) to 8(death) for subjects taking opaganib and those on placebo, lower scores indicate improvement. Success was defined as subject who reached improvement of at least two points on the WHO Ordinal Scale by Day 14, maintained by the end of study visit, and failure otherwise.

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Percentage of Subjects With ≥ 2 Category Improvement on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 Subject has improvement > or equal to 2 on the WHO Ordinal Scale Day 14 and up to to Day 42	145 Participants	138 Participants
Percentage of Subjects With ≥ 2 Category Improvement on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 Subject has improvement of 1 or none on the WHO Ordinal Scale (Failure) Day 14 up to Day 42	85 Participants	95 Participants
Percentage of Subjects With ≥ 2 Category Improvement on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 Failure due to not achieving improvement at Day 14	64 Participants	69 Participants
Percentage of Subjects With ≥ 2 Category Improvement on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 Failure due to death up to Day 14 (before any success)	18 Participants	21 Participants
Percentage of Subjects With ≥ 2 Category Improvement on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 Failure due to missing status at Day 42 with prior success	3 Participants	5 Participants

SECONDARY outcome

Timeframe: 14 days maintained up to 42 days

Population: mITT population presenting subjects who experienced a recovery event by Day 14 maintained up to day 42

Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement to determine time to recovery as defined by improvement to a score of 3 or less on the WHO Ordinal Scale for Clinical Improvement with a scale ranging from 0 (uninfected) to 8 (death)

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Subjects With Improvement to a Score of 3 or Less on the WHO Ordinal Scale for Clinical Improvement With a Scale Ranging From 8 Down to 0	145 Participants	138 Participants

SECONDARY outcome

Timeframe: 14 days maintained up to 42 days

Population: mITT. In this analysis, subjects who required low-flow supplemental oxygen at Day 1 (baseline) were considered success events, and the time to event of interest for these subjects was defined as 0.

To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Participants With Low Oxygen Flow Via Nasal Cannula	169 Participants	167 Participants

SECONDARY outcome

Timeframe: 14 days

Population: mITT

Time to subject discharge from hospital

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Time to Discharge From Hospital Measured at 14 Days	13.50 Days Interval 12.0 to 15.0	14.00 Days Not achieved

SECONDARY outcome

Timeframe: 42 days

Population: Subjects requiring intubation by Day 42

To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Patients Requiring Intubation and Mechanical Ventilation by Day 42 Subjects requiring intubation and mechanical ventilation by Day 42 (Failure)	53 Participants	57 Participants
Patients Requiring Intubation and Mechanical Ventilation by Day 42 Subjects not requiring intubation and mechanical ventilation by Day 42 (Success)	177 Participants	176 Participants
Patients Requiring Intubation and Mechanical Ventilation by Day 42 Type of failure: Intubation without death	10 Participants	10 Participants
Patients Requiring Intubation and Mechanical Ventilation by Day 42 Type of failure: Intubation with death	33 Participants	33 Participants
Patients Requiring Intubation and Mechanical Ventilation by Day 42 Type of failure: Death without intubation	3 Participants	5 Participants
Patients Requiring Intubation and Mechanical Ventilation by Day 42 Type of failure: Early termination/missing data (alive without intubation)	7 Participants	9 Participants

SECONDARY outcome

Timeframe: 14 days

Population: Only subjects who were positive for SARS-CoV-2 by PCR at the screening visit were analyzed

To compare the number of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=218 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=219 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 Number of participants	93 participants	79 participants
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 Number of censored participants (observations)	125 participants	140 participants
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 Participants with no post baseline results available	13 participants	8 participants
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 Participants with less than two results and discharged by Day 5	7 participants	7 participants
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 Participants with less than two results and not discharged by Day 5	21 participants	24 participants
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 Participants with at least two results which are not two sequential negatives	84 participants	101 participants

SECONDARY outcome

Timeframe: 14 days

Population: Only subjects who were positive for SARS-CoV-2 by PCR at the screening visit AND had at least two post baseline PCR tests were analyzed.

To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=177 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=180 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Patients With Negative Swabs for SARS-CoV-2 at Day 14 Participants without two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 (Failure)	93 Participants	79 Participants
Patients With Negative Swabs for SARS-CoV-2 at Day 14 Participants with at least two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 (Success)	84 Participants	101 Participants

SECONDARY outcome

Timeframe: 28 days

Population: Mortality ("failure") was assessed by treatment Day 28 (including). Any early termination/ missing survival status at the end of study visit was also regarded as failure for the primary analysis of this endpoint.

To compare mortality 28 days post-baseline between subjects taking opaganib and those taking placebo

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Mortality Due to Any Cause Yes (Failure) - Mortality due to any cause at Day 28	38 Participants	44 Participants
Mortality Due to Any Cause No (Success)	192 Participants	189 Participants

SECONDARY outcome

Timeframe: 42 days

Population: Mortality ("failure") was assessed by treatment Day 42 (including). Any early termination/ missing survival status at the end of study visit was also regarded as failure for the primary analysis of this endpoint.

To compare mortality 42 days post-baseline between subjects taking opaganib and those taking placebo

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Mortality Due to Any Cause Yes (Failure) - Mortality due to any cause at Day 42	44 Participants	47 Participants
Mortality Due to Any Cause No (Success)	186 Participants	186 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose until 4 weeks follow-up after the end of treatment

Population: TEAE=Treatment emergent adverse event. Treatment emergent events are events that started on or after the date of first dose

To compare the number of participants with treatment emergent adverse events (TEAEs) in patients with severe COVID-19 pneumonia between participants taking opaganib and participants taking placebo

Outcome measures

Outcome measures
Measure	Opaganib n=230 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=233 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	155 Participants	147 Participants

POST_HOC outcome

Timeframe: Day 14

Population: A post hoc analysis set comprised two sub-populations, namely, "lower FiO2" (FiO2 at baseline ≤ the median of 60%) and "higher FiO2" (FiO2 at baseline \> the median of 60%) was added after the final version of the SAP was signed.

Percentage of Subjects No Longer Requiring Supplemental Oxygen, for at Least 24 Hours by Day 14 in the ≤60% FiO2 FiO2 Sub-populations

Outcome measures

Outcome measures
Measure	Opaganib n=117 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=134 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population Subjects no longer requiring oxygen for at least 24 hours by Day 14	90 Participants	85 Participants
Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population Subjects requiring oxygen (including death, lost to follow-up or need of oxygen)	27 Participants	49 Participants

POST_HOC outcome

Timeframe: Day 14

Percentage of Subjects No Longer Requiring Supplemental Oxygen, for at Least 24 Hours by Day 14 in the \> 60% FiO2 FiO2 Sub-populations

Outcome measures

Outcome measures
Measure	Opaganib n=105 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=88 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population Subjects no longer requiring oxygen for at least 24 hours by Day 14	43 Participants	41 Participants
Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population Subjects requiring oxygen (including death, lost to follow-up or need of oxygen)	62 Participants	47 Participants

POST_HOC outcome

Timeframe: 14 days maintained up to 42 days or classified as a failure

Post hoc analysis in the FiO2 ≤ 60% population. Compare ≥2 category improvement on the WHO Ordinal Scale for subjects taking opaganib and those on placebo, lower scores indicate improvement. Success was defined as subject who reached improvement of at least two points on the WHO Ordinal Scale by Day 14, maintained by the end of study visit day 42, and failure otherwise. WHO Ordinal Scale for Clinical Improvement is a scale from 0 (uninfected) to 8 (death) with higher scale poorer clinical status

Outcome measures

Outcome measures
Measure	Opaganib n=117 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=134 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 in the FiO2 ≤ 60% Population Subject has improvement of 2 or more on the WHO Ordinal Scale (Success) Day 14 maintained to day 42	93 Participants	88 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 in the FiO2 ≤ 60% Population Subject has improvement of 1 or does not show improvement on the WHO Ordinal Scale (Failure) Day 14	24 Participants	46 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 in the FiO2 ≤ 60% Population Failure due to not achieving improvement at Day 14	21 Participants	29 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 in the FiO2 ≤ 60% Population Failure due to death up to Day 14 (before any success)	3 Participants	13 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42 in the FiO2 ≤ 60% Population Failure due to missing status at Day 42 with prior success at Day 14	0 Participants	4 Participants

POST_HOC outcome

Timeframe: 14 days maintained up to 42 days or classifed as failure

Post hoc analysis in the FiO2 \> 60% population. Compare ≥2 category improvement on the WHO Clinical Ordinal Scale for subjects taking opaganib and those on placebo, lower scores indicate improvement. Success was defined as subject who reached improvement of at least two points on the WHO Ordinal Scale by Day 14, maintained by the end of study visit day 42 and failure otherwise.WHO Scale 0 to 8 with 8 death and higher number worse clinical state

Outcome measures

Outcome measures
Measure	Opaganib n=105 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=88 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 up to Day 42 in the FiO2 > 60% Population Subject has improvement of 2 or more on the WHO Ordinal Scale (Success) Day 14 maintained to Day 42	46 Participants	43 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 up to Day 42 in the FiO2 > 60% Population Subject has improvement of 1 or no improvement shown on the WHO Ordinal Scale (Failure) at Day 14	59 Participants	45 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 up to Day 42 in the FiO2 > 60% Population Failure due to not achieving improvement at Day 14	41 Participants	37 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 up to Day 42 in the FiO2 > 60% Population Failure due to death up to Day 14 (before any success)	15 Participants	7 Participants
Subjects With ≥ 2 Category Improvement on the WHO Ordinal Scale for Clinical Improvement by Day 14 up to Day 42 in the FiO2 > 60% Population Failure due to missing status at Day 42 with prior success	3 Participants	1 Participants

POST_HOC outcome

Timeframe: 14 days

Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement. WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0 with a higher score indicating a poorer clinical status

Outcome measures

Outcome measures
Measure	Opaganib n=117 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=134 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Subjects With Improvement to a Score of 3 or Less on the WHO Ordinal Scale for Clinical Improvement in the FiO2 ≤60% Population	93 Participants	88 Participants

POST_HOC outcome

Timeframe: 14 days

Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement. World Health Organization Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0 with a higher score indicating poorer clincal status

Outcome measures

Outcome measures
Measure	Opaganib n=105 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=88 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Subjects With Improvement to a Score of 3 or Less on the WHO Ordinal Scale for Clinical Improvement in the FiO2 > 60% Population	46 Participants	43 Participants

POST_HOC outcome

Timeframe: 14 days

Subjects discharged from the hospital in the FiO2 ≤60% population at 14 days

Outcome measures

Outcome measures
Measure	Opaganib n=117 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=134 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Subjects Discharged From Hospital in the FiO2 ≤60% Population	81 Participants	85 Participants

POST_HOC outcome

Timeframe: 14 days

Number of subjects discharged from the hospital in the FiO2 \> 60% population

Outcome measures

Outcome measures
Measure	Opaganib n=105 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=88 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Number of Subjects Discharged From Hospital in the FiO2 > 60% Population	41 Participants	40 Participants

POST_HOC outcome

Timeframe: 42 days

Population: Subjects requiring intubation by Day 42 in the FiO2 ≤60% sub-population

To compare the proportion of patients in the FiO2 ≤60% sub-population requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=117 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=134 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population Subjects requiring intubation and mechanical ventilation by Day 42 (Failure)	8 Participants	24 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population Subjects not requiring intubation and mechanical ventilation by Day 42 (Success)	109 Participants	110 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population Type of failure: Intubation without death	2 Participants	3 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population Type of failure: Intubation with death	5 Participants	15 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population Type of failure: Death without intubation	0 Participants	1 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population Type of failure: Early termination/missing data (alive without intubation)	1 Participants	5 Participants

POST_HOC outcome

Timeframe: 42 days

Population: Subjects requiring intubation by Day 42 in the FiO2 ≤60% sub-population

To compare the proportion of patients in the FiO2 \> 60% sub-population requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

Outcome measures

Outcome measures
Measure	Opaganib n=105 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=88 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population Subjects requiring intubation and mechanical ventilation by Day 42 (Failure)	43 Participants	30 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population Subjects not requiring intubation and mechanical ventilation by Day 42 (Success)	62 Participants	58 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population Type of failure: Intubation without death	7 Participants	6 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population Type of failure: Intubation with death	28 Participants	16 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population Type of failure: Death without intubation	3 Participants	4 Participants
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population Type of failure: Early termination/missing data (alive without intubation)	5 Participants	4 Participants

POST_HOC outcome

Timeframe: 28 and 42 days

Population: Mortality ("failure") was assessed by treatment Day 28 (including) and Day 42. Any early termination/ missing survival status at the end of study visit was also regarded as failure for the primary analysis of this endpoint. For the FiO2 ≤60% Sub-population

To compare mortality 28 and 42 days post-baseline between subjects taking opaganib and those taking placebo in the in the FiO2 ≤60% population

Outcome measures

Outcome measures
Measure	Opaganib n=117 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=134 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Mortality Due to Any Cause in the FiO2 ≤60% Population Mortality due to any cause at Day 42 in the FiO2 ≤60% population · Yes (Failure) - Mortality due to any cause	7 Participants	21 Participants
Mortality Due to Any Cause in the FiO2 ≤60% Population Mortality due to any cause at Day 28 in the FiO2 ≤60% population · Yes (Failure) - Mortality due to any cause	7 Participants	21 Participants
Mortality Due to Any Cause in the FiO2 ≤60% Population Mortality due to any cause at Day 28 in the FiO2 ≤60% population · No (Success)	110 Participants	113 Participants
Mortality Due to Any Cause in the FiO2 ≤60% Population Mortality due to any cause at Day 42 in the FiO2 ≤60% population · No (Success)	110 Participants	113 Participants

POST_HOC outcome

Timeframe: 28 and 42 days

To compare mortality 28 and 42 days post-baseline between subjects taking opaganib and those taking placebo in the in the FiO2 \> 60% population

Outcome measures

Outcome measures
Measure	Opaganib n=105 Participants In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube. Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).	Placebo n=88 Participants In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube. Placebo: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Mortality Due to Any Cause in the FiO2 > 60% Population Mortality due to any cause at Day 28 in the FiO2 > 60% population · Yes (Failure)	30 Participants	21 Participants
Mortality Due to Any Cause in the FiO2 > 60% Population Mortality due to any cause at Day 28 in the FiO2 > 60% population · No (Success)	75 Participants	67 Participants
Mortality Due to Any Cause in the FiO2 > 60% Population Mortality due to any cause at Day 42 in the FiO2 > 60% population · Yes (Failure)	36 Participants	24 Participants
Mortality Due to Any Cause in the FiO2 > 60% Population Mortality due to any cause at Day 42 in the FiO2 > 60% population · No (Success)	69 Participants	64 Participants

Adverse Events

Opaganib

Serious events: 52 serious events

Other events: 155 other events

Deaths: 44 deaths

Placebo

Serious events: 52 serious events

Other events: 147 other events

Deaths: 47 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Raday, COO

RedHill Biopharma Ltd.

Phone: +972-(0)3-541-3131

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60