| Primary | Proportion of Patients Alive and Free of Respiratory Failure at Day 28 | The event variable is defined as "the proportion of patients alive and free of respiratory failure at Day 28". This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | participants | | At day 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
| | | Title | Denominators | Categories |
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Analysis is based on logistic regression model with Multiple Imputation under missing not at random using retrieve dropouts with proportion of patients alive and free of respiratory failure at Day 28 as dependent variable, treatment, age group, gender and presence of concomitant disease at baseline as qualitative independent variables. Site is considered as random effects that vary randomly among patients. | Two-sided regression, Logistic | | 0.216 | | Odds Ratio (OR) | 1.626 | | | 2-Sided | 95 | 0.752 | 3.514 | | | | | Superiority | | |
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| Secondary | Proportion of Patients Alive and Free of Respiratory Failure at Day 60 | This key secondary efficacy endpoint of the study is defined as "the proportion of patients alive and free of respiratory failure at Day 60", i.e. with no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the logistic regression model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Number | | participants | | At day 60 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Mortality Rates up to Day 28 | This key secondary efficacy endpoint describes number and proportion along with the 95% CI (Clopper-Pearson's formula) of patients who died up to Day 28. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the logistic regression model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Number | | participants | | Up to Day 28 | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Incidence of ICU Admission Until Day 28 | This is a key secondary efficacy endpoint. Admissions to Intensive Care Unit (ICU) had to be considered only in presence of significant worsening of respiratory status. This condition was objectively identified by means of a decrease of PaO2/FiO2 ratio of at least 40% from the baseline value or by a worsening of Investigator's Interpretation. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the logistic regression model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Number | | participants | | Until day 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28 | This is a key secondary efficacy endpoint. The event "recovery" was considered as such, if the patient has scored category 1, 2 or 3 from the 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), otherwise it will be considered free of event. Category 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; [4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death]. The lower the category, the better the outcome. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | number of patients with event (recovery) | | Until Day 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 |
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| Secondary | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | The event variable is defined as the proportion of patients alive and free of respiratory failure at fixed timepoints. This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. Admissions to ICU had to be considered only in presence of significant worsening of respiratory status. This condition was objectively identified by means of a decrease of PaO2/FiO2 ratio of at least 40% from the baseline value or by a worsening of Investigator's Interpretation. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | participants | | At Days 3, 7(±1),14(±2), 21(±2) and 90(±2) after randomization (randomization = day 1) | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo |
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| Secondary | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Changes from baseline in clinical severity score are analyzed based on the 7-point WHO-OS. The 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), comprises the following categories: 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; 4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death. | The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Mean | Standard Deviation | score on a scale | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 |
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| Secondary | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Clinical improvement 1 is defined as the decline of 1 category in the 7-point WHO-OS up to Date 28. The clinical improvement 1 up to Day 28 was analyzed as described for time to recovery: an event was considered as such, if patient declined of at least 1 category in the 7-point WHO-OS respect to the baseline, otherwise it was be considered free of event. | The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | number of patients with event | | Day 1 (baseline), Days 3, 7, 14, 21, 28. | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). | | OG001 | Placebo | placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. Placebo: Matched placebo, i.e. 2 tablets for the total of three daily administrations (6 tablets daily). |
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| Secondary | Percentage of Participants With Clinical Improvement 1 up to Day 28 | Clinical improvement 1 up to Date 28 for this outcome is expressed as cumulative incidence function (CIF in %). CIF allows for estimation of the occurrence of an event while taking into account the following competing risks: death, reasons for discontinuation for Adverse events and patient transferred to another institution. Estimates are calculated using a nonparametric method. The null hypothesis is that the cumulative incidence functions are identical across treatment groups. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | 95% Confidence Interval | % of participants | | At day 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Clinical improvement 2 is defined as the decline of 2 categories in the 7-point WHO-OS) up to Date 28. Clinical improvement 2 up to Date 28 was analyzed as described for time to recovery. An event was considered as such, if patient declined of at least 2 categories in the 7-point WHO-OS respect to the baseline, otherwise it was considered free of event. | The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | number of patients with event | | Day 1 (baseline), Days 3, 7, 14, 21, 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Percentage of Participants With Clinical Improvement 2 up to Day 28 | Clinical improvement 2 up to Day 28 is defined as cumulative incidence function (CIF, in %). CIF allows for estimation of the occurrence of an event while taking into account the following competing risks: death, reasons for discontinuation for Adverse events and patient transferred to another institution. Estimates are calculated using a nonparametric method. The null hypothesis is that the cumulative incidence functions are identical across treatment groups. | FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP. But FAS patients with at least one major (i.e. error in IMP administration, I/E criteria violation) or minor protocol deviation (i.e. not respecting visit schedule) up to Day 28 couldn't be considered in the analysis. | Posted | | Number | 95% Confidence Interval | Percentage of patients | | At Day 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo |
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| Secondary | Time to Discharge From Hospital up to Day 28 | Time to discharge from hospital up to Day 28 is analyzed as described for time to recovery. | FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | number of patients with event | | Day 1 (baseline), Days 3, 7, 14, 21, 28 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Clinical status is analyzed based on the 7-point WHO-OS. The 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), comprises the following categories: 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; 4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death. The higher the score, the worse the outcome. | FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | number of patients with event | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 |
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| Secondary | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | The number of patients with Dyspnea severity Likert scale by score and treatment group is calculated for each time point. Likert scale: grading the current experience of breathing discomfort compared to baseline (randomization) status (from -3 to 3) where: "-1 = minimally worse; -2 = moderately worse; -3 = markedly worse; 0 = no change; 1 = minimally better; 2 = moderately better; 3 = markedly better" More negative the score, the worse the outcome. | FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | participants | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | |
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| Secondary | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Peripheral oxygen saturation (SpO2) monitoring by pulse oximetry is used to estimate the oxygen saturation of arterial blood (SaO2) and provides vital information about a patient's cardiorespiratory function. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Mean | Standard Deviation | percentage of oxygenated hemoglobin | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | The pain VAS is a unidimensional measure of pain intensity, used to record patients' pain progression, or compare pain severity between paints with similar conditions.The VAS scale is from 0 to 100. The number 0 means the worst breathing the patient has ever felt, and the number 100 means the best the patient has ever felt. | FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Mean | Standard Deviation | score on a scale | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Duration of Supplemental Oxygen Treatment up to Day 28 | This endpoint is expressed as:
- The number and proportion along with the 95% CI (Clopper-Pearson's formula) of patients using supplemental oxygen treatment by treatment group;
- The Cumulative duration of supplemental oxygen treatment in days analyzed by means of descriptive statistics by treatment. This latter is reported in the system.
| FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Mean | Standard Deviation | day | | From baseline up to day 28 | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60 | Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. During mechanical ventilation, a predetermined mixture of air (ie, oxygen and other gases) is forced into the central airways and then flows into the alveoli. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model at Day 28 are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Number | | Number of patient with event | | day 28 and Day 60 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Duration of Non-invasive Mechanical Ventilation up to Day 60 | Non-invasive ventilation (NIV) is the delivery of oxygen (ventilation support) via a face mask and therefore eliminating the need of an endotracheal airway. NIV achieves comparative physiological benefits to conventional mechanical ventilation by reducing the work of breathing and improving gas exchange. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Mean | Standard Deviation | days | | From baseline up to day 60 | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60 | Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. During mechanical ventilation, a predetermined mixture of air (ie, oxygen and other gases) is forced into the central airways and then flows into the alveoli. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Mean | Standard Deviation | Days | | Up to day 60 | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Duration of ICU Admission up to Day 60 | Admission to intensive care unit or ICU is linked to worsening of respiratory parameters compared to baseline. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Mean | Standard Deviation | Days | | Up to day 60 | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | PaO2-the oxygen pressure in arterial blood. The PaO2 reflects how well oxygen is able to move from the lungs to the blood. It is often altered by severe illnesses, with the PaO2 test results used to guide treatment. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Mean | Standard Deviation | mmHg | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | The PaO2/FiO2 ratio is used to determine the severity of lung injury in mechanically ventilated patients. A normal P/F Ratio is ≥ 400 and equivalent to a PaO2 ≥ 80 mmHg on room air. Low values of the PaO2/FIO2 ratio may be due to pathological conditions, primarily those of a respiratory nature (atelectasis, ARDS, acute pulmonary edema, pneumonia, etc.), as well as to alterations in hemodynamic status (cardiogenic shock, septic shock, etc.), or even both. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Mean | Standard Deviation | PaO2/FiO2 Ratio | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | The high-sensitivity C-reactive protein (hs-CRP) test is more sensitive than the standard CRP test measuring slight increases in CRP levels even when within the normal range. Because of this greater sensitivity, the hs-CRP test can help determine your risk of cardiovascular disease (CVD). | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. Please note that the Number Analyzed per Row includes those participants who contributed data at the specified time point. | Posted | | Mean | Standard Deviation | mg/L | | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo |
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| Secondary | Mortality Rates up to Days 60 and 90 | Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. The death event variable is defined as the proportion of patients died up to Day 90. | FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. | Posted | | Number | | dead patients | | up to Days 60 and 90 | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). | | OG001 | Placebo | placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. Placebo: Matched placebo, i.e. 2 tablets for the total of three daily administrations (6 tablets daily). |
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| Secondary | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | Freedom from (time to) death or respiratory failure (need of invasive mechanical ventilation or ECMO or admission to ICU linked to worsening of respiratory parameters compared to baseline) at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90 was performed using the same Kaplan-Meier analysis and the one-sided log-rank test that were used to test for differences between groups. | The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. | Posted | | Number | | participants with event | | at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90 | | | | ID | Title | Description |
|---|
| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | | OG001 | Placebo | Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing. Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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| Secondary | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | AE= An adverse event is any untoward or unfavorable medical occurrence in a human. subject, including any abnormal sign (for example, abnormal physical exam or. laboratory finding), symptom, or disease, temporally associated with the subject's. serious AE=a SAE iA serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose results in death Is life-threatening Requires inpatient hospitalization or causes prolongation of existing hospitalization Results in persistent or significant disability/incapacity May have caused a congenital anomaly/birth defect Requires intervention to prevent permanent impairment or damage. The term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Do note that starting from this point the safety endpoint is analysed. | The Safety set (SAF) consisted of all randomized subjects who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data. | Posted | | Number | | number of subjects | | Throughout the study, till Day 90 (= end of the follow-up period). | | | | ID | Title | Description |
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| OG000 | Reparixin | Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. |
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