Trial Outcomes & Findings for Reparixin in COVID-19 Pneumonia - Efficacy and Safety (NCT NCT04794803)

NCT ID: NCT04794803

Last Updated: 2024-01-08

Results Overview

Composite event is defined as the onset of at least one of the following events: * supplemental oxygen requirement based on a worsening of PaO2/FiO2 ratio, * invasive mechanical ventilation use, * admission to Intensive Care Unit (ICU), * use of a rescue medication for any reason. Please note that in the measure type "number" actually is a "rate" of patients. Rate is referred to a binomial response rate while the 95% CIs are estimated by using the Clopper-Pearson's method

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

56 participants

Primary outcome timeframe

Up to Day 1

Results posted on

2024-01-08

Participant Flow

A total of 56 patients were screened and all of them were randomized to the assigned treatment group: 37 patients were randomised to receive Reparixin and 19 patients were randomised to receive standard of care.

Participant milestones

Participant milestones
Measure
Reparixin
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care
Standard of care Standard of care: Standard of care
Overall Study
STARTED
37
19
Overall Study
FAS Population
36
19
Overall Study
Safety Set
36
19
Overall Study
Per Protocol Set
17
11
Overall Study
COMPLETED
27
11
Overall Study
NOT COMPLETED
10
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Reparixin
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care
Standard of care Standard of care: Standard of care
Overall Study
Death
1
3
Overall Study
Lost to Follow-up
2
2
Overall Study
Withdrawal by Subject
1
0
Overall Study
Physician Decision
1
1
Overall Study
Patient transferred to another centre for oxygen rehabilitation
4
1
Overall Study
Refused to continue the treatment
1
0
Overall Study
Patient admitted to ICU
0
1

Baseline Characteristics

Reparixin in COVID-19 Pneumonia - Efficacy and Safety

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Total
n=55 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
22 Participants
n=5 Participants
11 Participants
n=7 Participants
33 Participants
n=5 Participants
Age, Categorical
>=65 years
14 Participants
n=5 Participants
8 Participants
n=7 Participants
22 Participants
n=5 Participants
Age, Continuous
60.6 years
STANDARD_DEVIATION 13.5 • n=5 Participants
63.6 years
STANDARD_DEVIATION 14.2 • n=7 Participants
61.6 years
STANDARD_DEVIATION 13.7 • n=5 Participants
Sex: Female, Male
Female
10 Participants
n=5 Participants
3 Participants
n=7 Participants
13 Participants
n=5 Participants
Sex: Female, Male
Male
26 Participants
n=5 Participants
16 Participants
n=7 Participants
42 Participants
n=5 Participants
Race/Ethnicity, Customized
Black or African American
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic or Latino
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Race/Ethnicity, Customized
Not Hispanic Or Latino
18 Participants
n=5 Participants
8 Participants
n=7 Participants
26 Participants
n=5 Participants
Race/Ethnicity, Customized
Not reported
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
Unknown
11 Participants
n=5 Participants
8 Participants
n=7 Participants
19 Participants
n=5 Participants
Race/Ethnicity, Customized
White/Caucasian
32 Participants
n=5 Participants
16 Participants
n=7 Participants
48 Participants
n=5 Participants
Race/Ethnicity, Customized
Black Or African American
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Brown
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
Other Ethnic Group
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Region of Enrollment
Brazil
2 participants
n=5 Participants
2 participants
n=7 Participants
4 participants
n=5 Participants
Region of Enrollment
Italy
34 participants
n=5 Participants
17 participants
n=7 Participants
51 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 1

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data.

Composite event is defined as the onset of at least one of the following events: * supplemental oxygen requirement based on a worsening of PaO2/FiO2 ratio, * invasive mechanical ventilation use, * admission to Intensive Care Unit (ICU), * use of a rescue medication for any reason. Please note that in the measure type "number" actually is a "rate" of patients. Rate is referred to a binomial response rate while the 95% CIs are estimated by using the Clopper-Pearson's method

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Composite event
16.7 percentage of participants
Interval 6.4 to 32.8
42.1 percentage of participants
Interval 20.3 to 66.5
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Supplemental oxygen requirement based on PaO2/FiO2
13.9 percentage of participants
Interval 4.7 to 29.5
26.3 percentage of participants
Interval 9.1 to 51.2
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Invasive Mechanical ventilation
2.8 percentage of participants
Interval 0.1 to 14.5
5.3 percentage of participants
Interval 0.1 to 26.0
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Admission to ICU
2.8 percentage of participants
Interval 0.1 to 14.5
0.0 percentage of participants
Interval 0.0 to 17.6
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Use of a rescue medication for any reason
0.0 percentage of participants
Interval 0.0 to 9.7
26.3 percentage of participants
Interval 9.1 to 51.2

SECONDARY outcome

Timeframe: At day 1, day 2, week 1, day 21(end of treatment, EOT), EOS (end of study, i.e. 7±3 days after EOT)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Changes in clinical severity score are defined as the time to clinical improvement of two points from the time of randomization on a seven-category ordinal scale or live discharge from the hospital, whichever came first. The seven-category ordinal scale consisted of the following: 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 Extracorporeal Membrane Oxygenation (ECMO), invasive mechanical ventilation, or both; and 7) death. The higher the score, the worse the outcome. A subject is considered "improved" with a clinical severity score improvement of at least two points compared to randomization or live discharge from the hospital. n are the subjects improved at each time point vs baseline.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
Day 1
0.0 Percentage of patients
Interval 0.0 to 10.0
0.0 Percentage of patients
Interval 0.0 to 17.6
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
Day 2
0.0 Percentage of patients
Interval 0.0 to 10.0
0.0 Percentage of patients
Interval 0.0 to 18.5
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
Week 1
23.5 Percentage of patients
Interval 10.7 to 41.2
17.6 Percentage of patients
Interval 3.8 to 43.4
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
EOT
26.5 Percentage of patients
Interval 12.9 to 44.4
26.3 Percentage of patients
Interval 9.1 to 51.2
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
EOS
61.5 Percentage of patients
Interval 40.6 to 79.8
55.6 Percentage of patients
Interval 21.2 to 86.3

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

The severity of dyspnea can be measured through the Liker scale. The Liker scale is used as follows: the patient grades his current breathing compared to when he first started the drug (from -3 to 3). "0" = no change, "1" =minimally better, "2" =moderately better, "3" =markedly better, "-1" =minimally worse, "-2" =moderately worse, "-3" =markedly worse. The higher the score, the better the outcome. N is the number of subjects for which the evaluation of the dyspnea severity scale at each time point is available. n is the number of subjects improved at each time point in comparison with the randomization.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
Baseline
0 Participants
1 Participants
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
Day 1
7 Participants
2 Participants
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
Day 2
12 Participants
2 Participants
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
Week 1
23 Participants
6 Participants
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
EOT
20 Participants
6 Participants
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
EOS
16 Participants
3 Participants

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)

Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP. Please note that N (36 for Reparixin and 19 for SoC) is the number of subjects for which the evaluation of the dyspnea severity scale at each time point is available. n - hereunder reported (28 for Reparixin and 19 for SoC) - is the number of subjects improved at each time point in comparison with the randomization.

The severity of dyspnea is measured also through the VAS scale. The VAS scale is used as follows: the patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt. N is the number of subjects for which the evaluation of the dyspnea severity scale at each time point is available. n is the number of subjects improved at each time point in comparison with the randomization.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
Baseline
56.9 score on a scale
Standard Deviation 37.3
4.0 score on a scale
Standard Deviation 5.5
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
to Day 1
4.3 score on a scale
Standard Deviation 8.5
20.0 score on a scale
Standard Deviation 40.0
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
to Day 2
32.3 score on a scale
Standard Deviation 40.3
44.8 score on a scale
Standard Deviation 51.7
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
Week 1
29.0 score on a scale
Standard Deviation 34.0
86.0 score on a scale
Standard Deviation 5.3
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
EOT
33.0 score on a scale
Standard Deviation 41.8
89.7 score on a scale
Standard Deviation 0.6
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
EOS
22.5 score on a scale
Standard Deviation 31.8

SECONDARY outcome

Timeframe: Baseline, Day 1, Day 2, Week 1, EOT and EOS

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Variations in the mean body temperature from baseline to any post-baseline timepoint were assessed. n is the number of subjects for which the evaluation of the body temperature at each time point is available.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
Baseline
36.4 F°
Standard Deviation 0.5
36.5 F°
Standard Deviation 0.5
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
to Day 1
-0.2 F°
Standard Deviation 0.5
0.2 F°
Standard Deviation 0.9
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
to Day 2
-0.1 F°
Standard Deviation 0.7
-0.1 F°
Standard Deviation 0.6
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
to Week 1
-0.1 F°
Standard Deviation 0.6
-0.2 F°
Standard Deviation 0.6
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
to EOT
-0.2 F°
Standard Deviation 0.6
-0.4 F°
Standard Deviation 0.6
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
to EOS
-0.1 F°
Standard Deviation 0.5
-0.5 F°
Standard Deviation 0.6

SECONDARY outcome

Timeframe: At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Cumulative quantity of oxygen treatment (L) = Sum of all Quantity (L) in CONCOMITANT OXYGEN TREATMENT form, from randomization to time point of interest. According to PaO2/FiO2, the classification is 'mild' if 200 \<= PaO2/FiO2 \< 300 mmHg, 'moderate' if 100 \<= PaO2/FiO2 \< 200 mmHg, 'severe' if PaO2/FiO2 \< 100 mmHg. A patient with ARDS (PaO2/FiO2\<300 mmHg) is considered 'worsened' in case of a decrease of PaO2/FiO2 of at least one third (-33,3%) from the baseline PaO2/FiO2 value. NOTE that: N is the number of subjects for which the evaluation of the PaO2/FiO2 ratio at each time point is available. While n is the number of subjects worsened at each time point in comparison with the randomization, expressed in percentage.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
Day 1 - subjects worsened (%)
7.4 percentage of subjects
Interval 0.9 to 24.3
14.3 percentage of subjects
Interval 1.8 to 42.8
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
Day 2 - subjects worsened (%)
12.9 percentage of subjects
Interval 3.6 to 29.8
20.0 percentage of subjects
Interval 4.3 to 48.1
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
Week 1 - subjects worsened (%)
0.0 percentage of subjects
Interval 0.0 to 13.2
21.4 percentage of subjects
Interval 4.7 to 50.8
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
EOT - subjects worsened (%)
0.0 percentage of subjects
Interval 0.0 to 11.9
8.3 percentage of subjects
Interval 0.2 to 38.5
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
EOS - subjects worsened (%)
0.0 percentage of subjects
Interval 0.0 to 30.8
0.0 percentage of subjects
Interval 0.0 to 70.8

SECONDARY outcome

Timeframe: day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Duration of oxygen administration (hours) = Administration end date/time - Administration start date/time / 60. N is the number of subjects for which the evaluation of the Oxygen Delivery System Classification at each time point is available. n is the number of subjects worsened at each time point, expressed in percentage, in comparison with the randomization. According to Oxygen Delivery System, the classification is 'invasive' if there is Invasive Medicinal Ventilation or ECMO, else 'high flow' if there is High Flow Nasal Cannula or BIPAP or CPAP, else 'low flow' if there is Nasal Cannula or Mask then Class=Low Flow Classification. A patient is considered 'Worsened' after baseline if there is an increase in the level of severity within the oxygen delivery system classification (Invasive \> High Flow \> Low Flow).

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
Day 2 - subjects worsened
5.6 percentage of patients
Interval 0.7 to 18.7
5.3 percentage of patients
Interval 0.1 to 26.0
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
Week 1 - subjects worsened
2.9 percentage of patients
Interval 0.1 to 15.3
17.6 percentage of patients
Interval 3.8 to 43.4
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
EOT - subjects worsened
2.9 percentage of patients
Interval 0.1 to 14.9
15.8 percentage of patients
Interval 3.4 to 39.6
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
EOS - subjects worsened
3.6 percentage of patients
Interval 0.1 to 18.3
8.3 percentage of patients
Interval 0.2 to 38.5
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
Day 1 - subjects worsened
5.6 percentage of patients
Interval 0.7 to 18.7
0.0 percentage of patients
Interval 0.0 to 17.6

SECONDARY outcome

Timeframe: Week 1, EOT, EOS

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

This outcome assesses the oxygen cumulative duration during the study. N is the number of subjects for which the evaluation of the PaO2/FiO2 ratio or Oxygen Delivery System Classification at each time point is available. n is the number of subjects worsened at each time point in comparison with the randomization.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Oxygen Cumulative Duration During the Study
week 1
141.93 hours
Standard Deviation 55.68
130.22 hours
Standard Deviation 80.89
Phase 2 - Oxygen Cumulative Duration During the Study
EOT
151.55 hours
Standard Deviation 75.53
134.00 hours
Standard Deviation 86.21
Phase 2 - Oxygen Cumulative Duration During the Study
EOS
195.26 hours
Standard Deviation 198.62
155.71 hours
Standard Deviation 135.93

SECONDARY outcome

Timeframe: Week 1, EOT and EOS

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

In this endpoint is assessed the oxygen cumulative quantity needed at each single timepoint. N is the number of subjects for which the evaluation of the PaO2/FiO2 ratio or Oxygen Delivery System Classification at each time point is available. n is the number of subjects worsened at each time point in comparison with the randomization.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Oxygen Cumulative Quantity During the Study
Week 1
24.99 liters
Standard Deviation 22.22
29.20 liters
Standard Deviation 29.51
Phase 2 - Oxygen Cumulative Quantity During the Study
EOT
25.64 liters
Standard Deviation 22.16
29.73 liters
Standard Deviation 31.53
Phase 2 - Oxygen Cumulative Quantity During the Study
EOS
26.54 liters
Standard Deviation 22.31
33.38 liters
Standard Deviation 31.64

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Percentage along with the 95% confidence interval (Clopper-Pearson's formula) of subjects requiring mechanical ventilation are calculated and compared. N is the number of subjects for which the evaluation of the use of mechanical ventilation is available. n is the number, expressed in percentage, of subjects requiring mechanical ventilation, overall.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
Baseline - subjects requiring
11.1 percentage of subjects
Interval 3.1 to 26.1
10.5 percentage of subjects
Interval 1.3 to 33.1
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
Day1 - subjects requiring
11.1 percentage of subjects
Interval 3.1 to 26.1
10.5 percentage of subjects
Interval 1.3 to 33.1
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
Day 2 - subjects requiring
11.4 percentage of subjects
Interval 3.2 to 26.7
16.7 percentage of subjects
Interval 3.6 to 41.4
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
Week 1- subjects requiring
8.8 percentage of subjects
Interval 1.9 to 23.7
11.8 percentage of subjects
Interval 1.5 to 36.4
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
EOT - subjects requiring
8.6 percentage of subjects
Interval 1.8 to 23.1
5.3 percentage of subjects
Interval 0.1 to 26.0
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
EOS -subjects requiring
0.0 percentage of subjects
Interval 0.0 to 12.8
0.0 percentage of subjects
Interval 0.0 to 30.8

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Cumulative duration of mechanical ventilation (in hours) = Sum of duration of mechanical ventilation (hours) in mechanical ventilation form, from randomization to time point of interest. Duration of mechanical ventilation (hours) = End date/time - Start date/time / 60. n is the number of subjects for which the evaluation of the use of mechanical ventilation is available

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall
Week 1
162.54 hours
Standard Deviation 58.92
142.42 hours
Standard Deviation 44.89
Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall
EOT
149.99 hours
Standard Deviation 53.23
146.86 hours
Standard Deviation 43.80
Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall
EOS
179.51 hours
Standard Deviation 78.30
154.86 hours
Standard Deviation 56.52

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Percentage, along with the 95% confidence interval (Clopper-Pearson's formula), of subjects requiring ICU admission are calculated and compared.N is the number of subjects for which the evaluation of the ICU admission need is available.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
Baseline - subjects admitted to ICU
2.8 percentage of patients
Interval 0.1 to 14.5
5.3 percentage of patients
Interval 0.1 to 26.0
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
Day 1 - subjects admitted to ICU
2.8 percentage of patients
Interval 0.1 to 14.5
5.3 percentage of patients
Interval 0.1 to 26.0
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
Day 2 - subjects admitted to ICU
5.7 percentage of patients
Interval 0.7 to 19.2
5.6 percentage of patients
Interval 0.1 to 27.3
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
Week 1 - subjects admitted to ICU
2.9 percentage of patients
Interval 0.1 to 15.3
0.0 percentage of patients
Interval 0.0 to 19.5
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
EOT - subjects admitted to ICU
2.9 percentage of patients
Interval 0.1 to 14.9
0.0 percentage of patients
Interval 0.0 to 17.6
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
EOS - subjects admitted to ICU
0.0 percentage of patients
Interval 0.0 to 30.8
0.0 percentage of patients
Interval 0.0 to 12.8

SECONDARY outcome

Timeframe: Day 1, Day 2, Week 1, EOT, EOS

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Cumulative ICU stay was assessed at different timepoints and measured in days

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Cumulative ICU Stay
Day 1 - cumulative ICU stay
1.0 days
Interval 1.0 to 1.0
1.0 days
Interval 1.0 to 1.0
Phase 2 - Cumulative ICU Stay
Day 2 - cumulative ICU stay
2.0 days
Interval 2.0 to 2.0
2.0 days
Interval 2.0 to 2.0
Phase 2 - Cumulative ICU Stay
Week 1 - cumulative ICU stay
7.0 days
Interval 7.0 to 7.0
3.0 days
Interval 3.0 to 3.0
Phase 2 - Cumulative ICU Stay
EOT - cumulative ICU stay
6.0 days
Interval 6.0 to 6.0
3.0 days
Interval 3.0 to 3.0
Phase 2 - Cumulative ICU Stay
EOS - cumulative ICU stay
50.0 days
Interval 50.0 to 50.0
3.0 days
Interval 3.0 to 3.0

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP. Please note that N, hereunder reported, is the number of subjects for which the evaluation of the lung damage extension or lung damage exudation degree at each time point is available (very low at Day 1 and EOS time points in the "Reparixin" Arm and at the Day 1, 2, and Week 1 time points in the "Standard of Care" Arm).

Lung damage extensions is assessed by Chest CT or Rx. This damage can be as follows: "none", "trace", "mild", "moderate", or "severe". N is the number of subjects for which the evaluation of the lung damage extension at each time point is available.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Lung Damage Extension by Severity and by Timepoint
baseline - none
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
baseline - trace
1 participants
2 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
baseline - mild
9 participants
3 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
baseline - moderate
23 participants
11 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
baseline - severe
3 participants
3 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 1 - none
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 1 - trace
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 1 - mild
0 participants
1 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 1 - moderate
1 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 1 - severe
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 2 - none
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 2 - trace
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 2 - mild
0 participants
1 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 2 - moderate
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Day 2 - severe
1 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
week 1 - none
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
week 1- trace
1 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
week 1 - mild
6 participants
2 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
week 1 - moderate
4 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
week 1 - severe
1 participants
2 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOT - none
1 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOT - trace
3 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOT - mild
8 participants
2 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOT - moderate
3 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOT - severe
1 participants
2 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOS - none
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOS - trace
0 participants
0 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOS - mild
1 participants
1 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOS - moderate
1 participants
1 participants
Phase 2 - Lung Damage Extension by Severity and by Timepoint
EOS - severe
0 participants
0 participants

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

Lung exudation is assessed by Chest CT or Rx. This can be as follows: "none", "trace", "mild", "moderate", or "severe". N is the number of subjects for which the evaluation of the lung damage extension at each time point is available.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Lung Exudation by Severity and by Timepoint
baseline - none
32 participants
18 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
baseline - trace
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
baseline - mild
1 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
baseline - moderate
3 participants
1 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
baseline - severe
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 1 - none
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 1 - trace
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 1 - mild
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 1 - moderate
1 participants
1 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 1 - severe
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 2 - none
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 2 - trace
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 2 - mild
0 participants
1 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 2 - moderate
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
Day 2 - severe
1 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
week 1 - none
12 participants
3 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
week 1- trace
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
week 1 - mild
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
week 1 - moderate
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
week 1 - severe
12 participants
1 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOT - none
15 participants
3 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOT - trace
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOT - mild
1 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOT - moderate
0 participants
4 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOT - severe
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOS - none
2 participants
2 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOS - trace
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOS - mild
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOS - moderate
0 participants
0 participants
Phase 2 - Lung Exudation by Severity and by Timepoint
EOS - severe
0 participants
0 participants

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP. Please note that N, hereunder reported, is the number of subjects for which the evaluation of the PaO2 at each time point is available (very low at Day 1 and EOS time points in the "Reparixin" Arm and at the Day 1, 2, and Week 1 time points in the "Standard of Care" Arm).

PaO2 measures the pressure of oxygen dissolved in the blood and how well oxygen is able to move from the airspace of the lungs into the blood. Normally, PaO2 is between 75 and 100 mmHg (at sea level). Lower levels indicate an unsufficient amount of oxygen flowing from the alveoli to the blood. Please note that a significant proportion of patients in both groups did not have post-baseline assessments of PaO2.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
Baseline
121.69 mmHg
Standard Deviation 47.15
68.64 mmHg
Standard Deviation 9.23
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
to Day 1
-19.61 mmHg
Standard Deviation 50.09
14.20 mmHg
Standard Deviation 25.76
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
to Day 2
12.62 mmHg
Standard Deviation 60.20
-4.68 mmHg
Standard Deviation 14.03
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
to week 1
11.76 mmHg
Standard Deviation 25.26
-1.13 mmHg
Standard Deviation 54.80
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
to EOT
8.01 mmHg
Standard Deviation 36.08
-18.70 mmHg
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
to EOS
-35.76 mmHg
Standard Deviation 47.84
1.80 mmHg

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

SpO2 measures the amount of oxygen-carrying hemoglobin in the blood relative to the amount of hemoglobin not carrying oxygen. Acceptable normal ranges for patients without pulmonary pathology are from 95 to 99 percent.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
Baseline
95.79 percent of oxygen saturation
Standard Deviation 3.17
94.97 percent of oxygen saturation
Standard Deviation 2.60
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
to Day 1
0.17 percent of oxygen saturation
Standard Deviation 2.20
-0.41 percent of oxygen saturation
Standard Deviation 3.57
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
to Day 2
0.38 percent of oxygen saturation
Standard Deviation 2.88
-0.63 percent of oxygen saturation
Standard Deviation 3.86
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
to week 1
1.18 percent of oxygen saturation
Standard Deviation 3.34
0.73 percent of oxygen saturation
Standard Deviation 3.71
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
to EOT
0.88 percent of oxygen saturation
Standard Deviation 3.57
1.19 percent of oxygen saturation
Standard Deviation 3.89
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
to EOS
0.47 percent of oxygen saturation
Standard Deviation 3.17
-4.00 percent of oxygen saturation
Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage) also known as the Horowitz index, the Carrico index, and (most conveniently) the P/F ratio at sea level, the normal PaO2/FiO2 ratio is \~ 400-500 mmHg (\~55-65 kPa).

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
Baseline
186.82 ratio
Standard Deviation 64.86
196.91 ratio
Standard Deviation 58.49
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
To day 1
21.58 ratio
Standard Deviation 65.81
6.08 ratio
Standard Deviation 125.00
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
To day 2
48.29 ratio
Standard Deviation 154.49
-8.53 ratio
Standard Deviation 71.74
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
To week 1
160.80 ratio
Standard Deviation 137.83
54.28 ratio
Standard Deviation 138.36
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
To EOT
171.27 ratio
Standard Deviation 149.56
74.65 ratio
Standard Deviation 113.55
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
To EOS
199.26 ratio
Standard Deviation 85.45
84.87 ratio
Standard Deviation 67.92

SECONDARY outcome

Timeframe: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP. The FAS population was analyzed according to intention to treat (ITT) principle, i.e. by treatment allocation regardless the occurrence of intercurrent events. The FAS population was used for the primary analyses of the study and to present results on efficacy data;

For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). Levels between 10 mg/L and 100 mg/L are moderately elevated and are usually due to more significant inflammation from an infectious or non-infectious cause. Inflammatory status is documented by C-reactive protein (CRP) ≥ 100mg/L.

Outcome measures

Outcome measures
Measure
Reparixin (FAS)
n=36 Participants
Reparixin oral tablets 1200 mg TID for 7 days Reparixin: Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (FAS)
n=19 Participants
Standard of care Standard of care: Standard of care
Phase 2 - Change From Baseline in Reactive Protein (CRP)
baseline
57.04 mg/L
Standard Deviation 41.44
58.87 mg/L
Standard Deviation 57.25
Phase 2 - Change From Baseline in Reactive Protein (CRP)
to day 1
-0.14 mg/L
Standard Deviation 73.28
38.46 mg/L
Standard Deviation 117.19
Phase 2 - Change From Baseline in Reactive Protein (CRP)
to day 2
-29.24 mg/L
Standard Deviation 37.66
-2.15 mg/L
Standard Deviation 52.37
Phase 2 - Change From Baseline in Reactive Protein (CRP)
to week 1
-39.09 mg/L
Standard Deviation 56.56
0.52 mg/L
Standard Deviation 80.24
Phase 2 - Change From Baseline in Reactive Protein (CRP)
to EOT
-40.88 mg/L
Standard Deviation 50.27
-25.28 mg/L
Standard Deviation 87.16
Phase 2 - Change From Baseline in Reactive Protein (CRP)
to EOS
-49.43 mg/L
Standard Deviation 57.65
-45.20 mg/L
Standard Deviation 78.97

Adverse Events

Reparixin (SAF)

Serious events: 1 serious events
Other events: 1 other events
Deaths: 1 deaths

Standard of Care (SAF)

Serious events: 1 serious events
Other events: 1 other events
Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure
Reparixin (SAF)
n=36 participants at risk
Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (SAF)
n=19 participants at risk
Standard of care, which is defined as any drug currently used to treat the COVID-19 pneumonia.
Respiratory, thoracic and mediastinal disorders
Respiratory failure
2.8%
1/36 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
5.3%
1/19 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).

Other adverse events

Other adverse events
Measure
Reparixin (SAF)
n=36 participants at risk
Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
Standard of Care (SAF)
n=19 participants at risk
Standard of care, which is defined as any drug currently used to treat the COVID-19 pneumonia.
Gastrointestinal disorders
Diarrhoea
2.8%
1/36 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
5.3%
1/19 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
Injury, poisoning and procedural complications
Post procedural discomfort
0.00%
0/36 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
5.3%
1/19 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
Respiratory, thoracic and mediastinal disorders
Respiratory failure
2.8%
1/36 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
5.3%
1/19 • Number of events 1 • Throughout the study, till day 21
The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).

Additional Information

Dr Maria De Pizzol, BSc

Dompé Farmaceutici

Phone: +39 02 583831

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place