COVID-19, Lung Infection
Conditions
Keywords
Therapeutic Use
Brief summary
A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.
Detailed description
This is a phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study with an adaptive design that will utilize a futility assessment. The study is planned be performed worldwide in up to approximately 80 clinical sites. After informed consent is obtained, patients will enter a screening phase for no more than 3 days, to determine eligibility. Approximately 464 eligible patients will be randomized and receive either opaganib added to standard of care, or matching placebo added to standard of care, in a randomization ratio of 1:1. Treatment assignments will remain blinded to the patient, investigator and hospital staff, as well as the sponsor. As the approval and/or guidance for treating COVID-19 are evolving, for this protocol, standard of care will be defined by the recommended schemes of treatment according to the severity of the disease, taking into consideration regulatory approvals in one or more regions. 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). All participants will be followed up for 28 days after their last dose of study drug, which may occur at Day 14 or after premature study drug discontinuation, based upon patient or physician determination.
Interventions
DRUGOpaganib
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).
DRUGPlacebo
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).
Sponsors
RedHill Biopharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Adult male or female ≥18 to ≤80 years of age 2. Proven COVID-19 infection per RT-PCR assay of a pharyngeal sample (nasopharyngeal or oropharyngeal) AND pneumonia defined as radiographic opacities on chest X-ray or CT scan. that diagnosed COVID-19 pneumonia. Pharyngeal samples collected either at screening or within 7-days prior to screening for the same ongoing COVID-19 pneumonia illness are acceptable 3. The patient requires, at baseline, high flow supplemental oxygen or positive pressure ventilation or is receiving oxygen via face mask, such as a non-rebreather or reservoir mask, capable of delivering high concentrations of oxygen 4. Patient agrees to use appropriate methods of contraception during the study and 3 months after the last dose of study drug 5. The patient or legal representative has signed a written informed consent approved by the IRB/Ethics Committee
Exclusion criteria
1. Any co-morbidity that may add risk to the treatment in the judgment of the investigator, particularly patients with known cardiac conditions, and serious neuropsychiatric conditions such as psychosis or major depression 2. Requiring intubation and mechanical ventilation at baseline 3. Patient has a 'Do Not Intubate' and/or 'Do Not Resuscitate' order in place 4. Oxygen saturation \>95% on room air 5. Any preexisting respiratory condition that requires intermittent or continuous ambulatory oxygen prior to hospitalization 6. Patient is, in the investigator's clinical judgement, unlikely to survive \>72 hours 7. Pregnant (positive serum or urine test within 3 days prior to randomization) or nursing women . 8. Unwillingness or inability to comply with procedures required in this protocol. 9. Corrected QT (QTc) interval on electrocardiogram (ECG) \>470 ms for females or \>450 ms for males, calculated using Friedericia's formula (QTcF) 10. AST (SGOT) or ALT (SGPT) \> 2.0 x upper limit of normal (ULN) 11. Total bilirubin \>1.5x ULN (except where bilirubin increase is due to Gilbert's Syndrome) 12. Serum creatinine \>2.0 X ULN 13. Absolute neutrophil count \<1000 cells/mm3 14. Platelet count \<75,000/mm3 15. Hemoglobin \<8.0 g/dL 16. Medications that are sensitive substrates, or substrates with a narrow therapeutic range, for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 CYP2D6 , CYP3A4, P-gP, BCRP and OATP1B1 should be avoided with opaganib 17. Moderate or strong inhibitors of CYP1A2, CYP3A4, CYP2D6 or P-gP or moderate to strong inducers of CYP3A4 and CYP1A2 are prohibited 18. Currently taking warfarin, apixaban, argatroban or rivaroxaban due to drug-drug interaction based on CYP450 metabolism 19. Current drug or alcohol abuse 20. Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies 21. Treatment with any medication that causes QT prolongation within seven days, or 5 half-lives, whichever is longest, prior to initiation of study drug, or intention to use them throughout the study, including but not limited to: amiodarone, amitriptyline, citalopram dose greater than 20 mg/day, dihydroergotamine, disopyramide, dofetilide, dronedarone, ergotamine, ibutilde, ondansetron or other 5-HT3 receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolone, ranolazine, risperidone, sotaloland tolteridine. Investigators are directed to the following up-to-date web site listing QT prolonging drugs: https://www.crediblemeds.org/index.php/drugsearch
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Supplemental Oxygen Requirement | 14 days maintained up to 42 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 14 days maintained up to 42 days | 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. |
| 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 | 14 days maintained up to 42 days | 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) |
| Number of Participants With Low Oxygen Flow Via Nasal Cannula | 14 days maintained up to 42 days | 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. |
| Time to Discharge From Hospital Measured at 14 Days | 14 days | Time to subject discharge from hospital |
| Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | 14 days | 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. |
| Patients With Negative Swabs for SARS-CoV-2 at Day 14 | 14 days | 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. |
| Mortality Due to Any Cause | 28 days | To compare mortality 28 days post-baseline between subjects taking opaganib and those taking placebo |
| Patients Requiring Intubation and Mechanical Ventilation by Day 42 | 42 days | To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose until 4 weeks follow-up after the end of treatment | 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 |
Countries
Brazil, Colombia, Israel, Italy, Mexico, Peru, Poland, Russia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Opaganib 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. | 237 |
| Placebo 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. | 238 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 35 | 39 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Missing study completion status | 3 | 1 |
| Overall Study | Other | 1 | 5 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 4 |
Baseline characteristics
| Characteristic | Opaganib | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 69 Participants | 117 Participants |
| Age, Categorical Between 18 and 65 years | 189 Participants | 169 Participants | 358 Participants |
| Age, Continuous | 55.6 Years STANDARD_DEVIATION 12.05 | 57.3 Years STANDARD_DEVIATION 12.74 | 56.5 Years STANDARD_DEVIATION 12.42 |
| BMI at Baseline (kg/m^2) | 31.02 kg/m2 STANDARD_DEVIATION 5.676 | 30.47 kg/m2 STANDARD_DEVIATION 5.158 | 30.74 kg/m2 STANDARD_DEVIATION 5.421 |
| FiO2>60% sub-population inflammation markers: CRP levels | 94.050 mg/L | 106.370 mg/L | 102.800 mg/L |
| FiO2≤60% sub-population inflammation markers: CRP Levels | 67.100 mg/L | 45.00 mg/L | 60.80 mg/L |
| FiO2≤60% sub-population inflammation markers: D-Dimer Levels | 0.499 ug/ml | 0.380 ug/ml | 0.450 ug/ml |
| FiO2>60% sub-population inflammation markers: D-Dimer Levels | 0.790 ug/ml | 0.836 ug/ml | 0.806 ug/ml |
| FiO2≤60% sub-population inflammation markers: Ferritin Levels | 727.600 ug/L | 592.300 ug/L | 666.950 ug/L |
| FiO2>60% sub-population inflammation markers: Ferritin Levels | 1074.150 ug/L | 980.00 ug/L | 1000.00 ug/L |
| FiO2≤60% sub-population inflammation markers: Lactate Dehydrogenase | 359.400 IU/L | 368.750 IU/L | 361.150 IU/L |
| FiO2>60% sub-population inflammation markers: Lactate Dehydrogenase Levels | 477.500 IU/L | 447.00 IU/L | 469.230 IU/L |
| FiO2≤60% sub-population inflammation markers: lymphocyte counts | 0.910 10^9*cell/L | 1.010 10^9*cell/L | 0.990 10^9*cell/L |
| FiO2>60% sub-population lymphocyte counts | 0.840 10^9*cell/L | 0.700 10^9*cell/L | 0.792 10^9*cell/L |
| HbA1c at Screening <6.5 and not on active treatment with insulin or oral hypoglycemics | 154 Participants | 157 Participants | 311 Participants |
| HbA1c at Screening ≥6.5 or on active treatment with insulin or oral hypoglycemics | 83 Participants | 80 Participants | 163 Participants |
| HbA1c at Screening Missing | 0 Participants | 1 Participants | 1 Participants |
| Median percentage of oxygen in the gas mix (%) | 60.0 Percentage of oxygen | 60.0 Percentage of oxygen | 60.0 Percentage of oxygen |
| Oxygen flow at baseline (L/min) | 24.6 L/min STANDARD_DEVIATION 19.59 | 24.9 L/min STANDARD_DEVIATION 19.83 | 24.8 L/min STANDARD_DEVIATION 19.69 |
| Oxygen in the gas mix (%) | 65.5 Percentage of oxygen STANDARD_DEVIATION 60 | 64.1 Percentage of oxygen STANDARD_DEVIATION 60 | 64.8 Percentage of oxygen STANDARD_DEVIATION 60 |
| Oxygen type (for supplemental oxygen at baseline - Yes) Intubation/Mechanical ventilation | 1 Participants | 2 Participants | 3 Participants |
| Oxygen type (for supplemental oxygen at baseline - Yes) Low Flow Nasal Cannulas (LFNC) | 3 Participants | 1 Participants | 4 Participants |
| Oxygen type (for supplemental oxygen at baseline - Yes) Non-invasive ventilation/High Flow Nasal Cannulas (HFNC)/Mask with reservoir/Mask without reservoir | 225 Participants | 230 Participants | 455 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants | 18 Participants | 41 Participants |
| Race (NIH/OMB) White | 197 Participants | 203 Participants | 400 Participants |
| Region of Enrollment Brazil | 61 participants | 62 participants | 123 participants |
| Region of Enrollment Colombia | 10 participants | 8 participants | 18 participants |
| Region of Enrollment Israel | 43 participants | 40 participants | 83 participants |
| Region of Enrollment Italy | 25 participants | 28 participants | 53 participants |
| Region of Enrollment Mexico | 7 participants | 4 participants | 11 participants |
| Region of Enrollment Poland | 12 participants | 16 participants | 28 participants |
| Region of Enrollment Russia | 79 participants | 80 participants | 159 participants |
| Sex: Female, Male Female | 86 Participants | 76 Participants | 162 Participants |
| Sex: Female, Male Male | 151 Participants | 162 Participants | 313 Participants |
| Supplemental Oxygen at Baseline Missing | 7 Participants | 5 Participants | 12 Participants |
| Supplemental Oxygen at Baseline No | 1 Participants | 0 Participants | 1 Participants |
| Supplemental Oxygen at Baseline Yes | 229 Participants | 233 Participants | 462 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 44 / 230 | 47 / 233 |
| other Total, other adverse events | 155 / 230 | 147 / 233 |
| serious Total, serious adverse events | 52 / 230 | 52 / 233 |
Outcome results
Primary
Supplemental Oxygen Requirement
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.
Time frame: 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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | Supplemental Oxygen Requirement | Subjects not receiving supplemental oxygen for at least 24 hours by Day 14 and maintained at Day 42 | 139 Participants |
| Opaganib | Supplemental Oxygen Requirement | Subjects receiving supplemental oxygen (including: death, lost to follow-up, or need of oxygen) | 91 Participants |
| Placebo | Supplemental Oxygen Requirement | Subjects not receiving supplemental oxygen for at least 24 hours by Day 14 and maintained at Day 42 | 132 Participants |
| Placebo | Supplemental Oxygen Requirement | Subjects receiving supplemental oxygen (including: death, lost to follow-up, or need of oxygen) | 101 Participants |
p-value: 0.39195% CI: [-4.93, 12.65]Cochran-Mantel-Haenszel
Secondary
Mortality Due to Any Cause
To compare mortality 42 days post-baseline between subjects taking opaganib and those taking placebo
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | Mortality Due to Any Cause | Yes (Failure) - Mortality due to any cause at Day 42 | 44 Participants |
| Opaganib | Mortality Due to Any Cause | No (Success) | 186 Participants |
| Placebo | Mortality Due to Any Cause | Yes (Failure) - Mortality due to any cause at Day 42 | 47 Participants |
| Placebo | Mortality Due to Any Cause | No (Success) | 186 Participants |
Secondary
Mortality Due to Any Cause
To compare mortality 28 days post-baseline between subjects taking opaganib and those taking placebo
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | Mortality Due to Any Cause | No (Success) | 192 Participants |
| Opaganib | Mortality Due to Any Cause | Yes (Failure) - Mortality due to any cause at Day 28 | 38 Participants |
| Placebo | Mortality Due to Any Cause | No (Success) | 189 Participants |
| Placebo | Mortality Due to Any Cause | Yes (Failure) - Mortality due to any cause at Day 28 | 44 Participants |
Secondary
Number of Participants With Low Oxygen Flow Via Nasal Cannula
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | Number of Participants With Low Oxygen Flow Via Nasal Cannula | 169 Participants |
| Placebo | Number of Participants With Low Oxygen Flow Via Nasal Cannula | 167 Participants |
p-value: 0.47295% CI: [0.87, 1.33]Log Rank
Secondary
Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14
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.
Time frame: 14 days
Population: Only subjects who were positive for SARS-CoV-2 by PCR at the screening visit were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Opaganib | Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | Number of participants | 93 participants |
| Opaganib | Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | Number of censored participants (observations) | 125 participants |
| Opaganib | Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | Participants with no post baseline results available | 13 participants |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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 |
| Placebo | Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | Number of participants | 79 participants |
| Placebo | 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 | 24 participants |
| Placebo | Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | Number of censored participants (observations) | 140 participants |
| Placebo | 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 | 101 participants |
| Placebo | Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14 | Participants with no post baseline results available | 8 participants |
p-value: 0.04395% CI: [0.99, 1.82]Log Rank
Secondary
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
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)
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | 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 |
| Placebo | 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 | 138 Participants |
p-value: 0.23195% CI: [0.91, 1.45]Log Rank
Secondary
Patients Requiring Intubation and Mechanical Ventilation by Day 42
To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.
Time frame: 42 days
Population: Subjects requiring intubation by Day 42
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Death without intubation | 3 Participants |
| Opaganib | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Intubation without death | 10 Participants |
| Opaganib | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Intubation with death | 33 Participants |
| Opaganib | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Early termination/missing data (alive without intubation) | 7 Participants |
| Opaganib | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Subjects requiring intubation and mechanical ventilation by Day 42 (Failure) | 53 Participants |
| Opaganib | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Subjects not requiring intubation and mechanical ventilation by Day 42 (Success) | 177 Participants |
| Placebo | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Intubation with death | 33 Participants |
| Placebo | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Subjects requiring intubation and mechanical ventilation by Day 42 (Failure) | 57 Participants |
| Placebo | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Intubation without death | 10 Participants |
| Placebo | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Death without intubation | 5 Participants |
| Placebo | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Subjects not requiring intubation and mechanical ventilation by Day 42 (Success) | 176 Participants |
| Placebo | Patients Requiring Intubation and Mechanical Ventilation by Day 42 | Type of failure: Early termination/missing data (alive without intubation) | 9 Participants |
p-value: 0.70195% CI: [-9.19, 6.18]Cochran-Mantel-Haenszel
Secondary
Patients With Negative Swabs for SARS-CoV-2 at Day 14
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.
Time frame: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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) | 79 Participants |
| Placebo | 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) | 101 Participants |
p-value: 0.11895% CI: [-2.05, 18.65]Cochran-Mantel-Haenszel
Secondary
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
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.
Time frame: 14 days maintained up to 42 days
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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 | 5 Participants |
| Placebo | 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 | 138 Participants |
| Placebo | 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 | 95 Participants |
| Placebo | 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 | 69 Participants |
| Placebo | 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) | 21 Participants |
p-value: 0.3895% CI: [-4.78, 12.6]Cochran-Mantel-Haenszel
Secondary
Time to Discharge From Hospital Measured at 14 Days
Time to subject discharge from hospital
Time frame: 14 days
Population: mITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Opaganib | Time to Discharge From Hospital Measured at 14 Days | 13.50 Days |
| Placebo | Time to Discharge From Hospital Measured at 14 Days | 14.00 Days |
p-value: 0.52195% CI: [0.846, 1.378]Log Rank
Post Hoc
Mortality Due to Any Cause in the FiO2 ≤60% 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
Time frame: 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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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) | 113 Participants |
| Placebo | 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 | 21 Participants |
| Placebo | 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 | 21 Participants |
| Placebo | 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) | 113 Participants |
p-value: 0.01995% CI: [-16.63, -1.8]Cochran-Mantel-Haenszel
Post Hoc
Mortality Due to Any Cause in the FiO2 > 60% 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
Time frame: 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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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) | 21 Participants |
| Placebo | 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) | 64 Participants |
| Placebo | 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) | 24 Participants |
| Placebo | 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) | 67 Participants |
p-value: 0.27395% CI: [-5.66, 20.39]Cochran-Mantel-Haenszel
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 155 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 147 Participants |
Post Hoc
Number of Subjects Discharged From Hospital in the FiO2 ≤60% Population
Subjects discharged from the hospital in the FiO2 ≤60% population at 14 days
Time frame: 14 days
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | Number of Subjects Discharged From Hospital in the FiO2 ≤60% Population | 81 Participants |
| Placebo | Number of Subjects Discharged From Hospital in the FiO2 ≤60% Population | 85 Participants |
p-value: 0.195% CI: [0.94, 1.732]Log Rank
Post Hoc
Number of Subjects Discharged From Hospital in the FiO2 > 60% Population
Number of subjects discharged from the hospital in the FiO2 \> 60% population
Time frame: 14 days
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | Number of Subjects Discharged From Hospital in the FiO2 > 60% Population | 41 Participants |
| Placebo | Number of Subjects Discharged From Hospital in the FiO2 > 60% Population | 40 Participants |
Post Hoc
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
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
Time frame: 14 days
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | 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 |
| Placebo | 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 | 88 Participants |
p-value: 0.0195% CI: [1.07, 1.93]Log Rank
Post Hoc
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
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
Time frame: 14 days
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Opaganib | 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 |
| Placebo | 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 | 43 Participants |
p-value: 0.54595% CI: [0.58, 1.34]Log Rank
Post Hoc
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% 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.
Time frame: 42 days
Population: Subjects requiring intubation by Day 42 in the FiO2 ≤60% sub-population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Type of failure: Intubation with death | 5 Participants |
| Opaganib | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Type of failure: Intubation without death | 2 Participants |
| Opaganib | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Type of failure: Death without intubation | 0 Participants |
| Opaganib | 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 |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Type of failure: Death without intubation | 1 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Subjects not requiring intubation and mechanical ventilation by Day 42 (Success) | 110 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Type of failure: Intubation without death | 3 Participants |
| Placebo | 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 |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Subjects requiring intubation and mechanical ventilation by Day 42 (Failure) | 24 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 ≤60% Population | Type of failure: Intubation with death | 15 Participants |
p-value: 0.01295% CI: [-18.44, -2.57]Cochran-Mantel-Haenszel
Post Hoc
Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% 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.
Time frame: 42 days
Population: Subjects requiring intubation by Day 42 in the FiO2 ≤60% sub-population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Intubation without death | 7 Participants |
| Opaganib | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Intubation with death | 28 Participants |
| Opaganib | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Death without intubation | 3 Participants |
| Opaganib | 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 |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Death without intubation | 4 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Subjects requiring intubation and mechanical ventilation by Day 42 (Failure) | 30 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Intubation with death | 16 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Subjects not requiring intubation and mechanical ventilation by Day 42 (Success) | 58 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Early termination/missing data (alive without intubation) | 4 Participants |
| Placebo | Requiring Intubation and Mechanical Ventilation by Day 42 in the FiO2 > 60% Population | Type of failure: Intubation without death | 6 Participants |
p-value: 0.30495% CI: [-6.46, 20.86]Cochran-Mantel-Haenszel
Post Hoc
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
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
Time frame: 14 days maintained up to 42 days or classified as a failure
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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 | 29 Participants |
| Placebo | 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 | 88 Participants |
| Placebo | 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 | 46 Participants |
| Placebo | 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) | 13 Participants |
| Placebo | 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 | 4 Participants |
p-value: 0.02395% CI: [1.9, 23.6]Cochran-Mantel-Haenszel
Post Hoc
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
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
Time frame: 14 days maintained up to 42 days or classifed as failure
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Opaganib | 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 |
| Placebo | 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 | 1 Participants |
| Placebo | 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) | 7 Participants |
| Placebo | 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 | 45 Participants |
| Placebo | 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 | 43 Participants |
| Placebo | 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 | 37 Participants |
p-value: 0.56195% CI: [-18.07, 9.82]Cochran-Mantel-Haenszel
Post Hoc
Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population
Percentage of Subjects No Longer Requiring Supplemental Oxygen, for at Least 24 Hours by Day 14 in the ≤60% FiO2 FiO2 Sub-populations
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population | Subjects no longer requiring oxygen for at least 24 hours by Day 14 | 90 Participants |
| Opaganib | Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population | Subjects requiring oxygen (including death, lost to follow-up or need of oxygen) | 27 Participants |
| Placebo | Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population | Subjects no longer requiring oxygen for at least 24 hours by Day 14 | 85 Participants |
| Placebo | Supplemental Oxygen Requirement in the ≤60% FiO2 Sub-population | Subjects requiring oxygen (including death, lost to follow-up or need of oxygen) | 49 Participants |
p-value: 0.03395% CI: [1.06, 23.5]Cochran-Mantel-Haenszel
Post Hoc
Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population
Percentage of Subjects No Longer Requiring Supplemental Oxygen, for at Least 24 Hours by Day 14 in the \> 60% FiO2 FiO2 Sub-populations
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Opaganib | Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population | Subjects no longer requiring oxygen for at least 24 hours by Day 14 | 43 Participants |
| Opaganib | Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population | Subjects requiring oxygen (including death, lost to follow-up or need of oxygen) | 62 Participants |
| Placebo | Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population | Subjects no longer requiring oxygen for at least 24 hours by Day 14 | 41 Participants |
| Placebo | Supplemental Oxygen Requirement in the > 60% FiO2 Sub-population | Subjects requiring oxygen (including death, lost to follow-up or need of oxygen) | 47 Participants |
p-value: 0.595% CI: [-18.67, 9.17]Cochran-Mantel-Haenszel