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Reparixin in COVID-19 Pneumonia - Efficacy and Safety

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04794803
Recruitment Status : Terminated (The sponsor has decided to start with a separate protocol for phase 3 and therefore this study was terminated with only phase 2.)
First Posted : March 12, 2021
Results First Posted : March 17, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Severe Pneumonia
Interventions Drug: Reparixin
Drug: Standard of care
Enrollment 56
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Reparixin Standard of Care
Hide Arm/Group Description

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

Period Title: Overall Study
Started 37 19
FAS Population 36 19
Safety Set 36 19
Per Protocol Set 17 11
Completed 27 11
Not Completed 10 8
Reason Not Completed
Death             1             3
Lost to Follow-up             2             2
Withdrawal by Subject             1             0
Physician Decision             1             1
Patient transferred to another centre for oxygen rehabilitation             4             1
Refused to continue the treatment             1             0
Patient admitted to ICU             0             1
Arm/Group Title Reparixin (FAS) Standard of Care (FAS) Total
Hide Arm/Group Description

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

Total of all reporting groups
Overall Number of Baseline Participants 36 19 55
Hide Baseline Analysis Population Description
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.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 19 participants 55 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
22
  61.1%
11
  57.9%
33
  60.0%
>=65 years
14
  38.9%
8
  42.1%
22
  40.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 19 participants 55 participants
60.6  (13.5) 63.6  (14.2) 61.6  (13.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 19 participants 55 participants
Female
10
  27.8%
3
  15.8%
13
  23.6%
Male
26
  72.2%
16
  84.2%
42
  76.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 19 participants 55 participants
Black or African American
1
   2.8%
0
   0.0%
1
   1.8%
Hispanic or Latino
3
   8.3%
2
  10.5%
5
   9.1%
Not Hispanic Or Latino
18
  50.0%
8
  42.1%
26
  47.3%
Not reported
3
   8.3%
1
   5.3%
4
   7.3%
Unknown
11
  30.6%
8
  42.1%
19
  34.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 19 participants 55 participants
White/Caucasian
32
  88.9%
16
  84.2%
48
  87.3%
Black Or African American
1
   2.8%
1
   5.3%
2
   3.6%
Brown
3
   8.3%
1
   5.3%
4
   7.3%
Other Ethnic Group
0
   0.0%
1
   5.3%
1
   1.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 19 participants 55 participants
Brazil 2 2 4
Italy 34 17 51
1.Primary Outcome
Title Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Hide Description

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
Time Frame Up to Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Composite event
16.7
(6.4 to 32.8)
42.1
(20.3 to 66.5)
Supplemental oxygen requirement based on PaO2/FiO2
13.9
(4.7 to 29.5)
26.3
(9.1 to 51.2)
Invasive Mechanical ventilation
2.8
(0.1 to 14.5)
5.3
(0.1 to 26.0)
Admission to ICU
2.8
(0.1 to 14.5)
0.0
(0.0 to 17.6)
Use of a rescue medication for any reason
0.0
(0.0 to 9.7)
26.3
(9.1 to 51.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.02164
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Sensitivity analysis of time to event for each single component of the primary endpoint: Supplemental oxygen requirement based on PaO2/FiO2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.20043
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Sensitivity analysis of time to event for each single component of the primary endpoint: time to first invasive mechanical ventilation
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.30215
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Sensitivity analysis of time to event for each single component of the primary endpoint: time to first admission to ICU
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56370
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Sensitivity analysis of time to event for each single component of the primary endpoint: time to first use of a rescue medication for any reason
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.00132
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
Hide Description

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.

Time Frame At day 1, day 2, week 1, day 21(end of treatment, EOT), EOS (end of study, i.e. 7±3 days after EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
Day 1 Number Analyzed 35 participants 19 participants
0.0
(0.0 to 10.0)
0.0
(0.0 to 17.6)
Day 2 Number Analyzed 35 participants 18 participants
0.0
(0.0 to 10.0)
0.0
(0.0 to 18.5)
Week 1 Number Analyzed 34 participants 17 participants
23.5
(10.7 to 41.2)
17.6
(3.8 to 43.4)
EOT Number Analyzed 34 participants 19 participants
26.5
(12.9 to 44.4)
26.3
(9.1 to 51.2)
EOS Number Analyzed 26 participants 9 participants
61.5
(40.6 to 79.8)
55.6
(21.2 to 86.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments comparison at week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.731
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
Hide Description 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.
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 11 participants 6 participants
0
   0.0%
1
  16.7%
Day 1 Number Analyzed 16 participants 9 participants
7
  43.8%
2
  22.2%
Day 2 Number Analyzed 16 participants 7 participants
12
  75.0%
2
  28.6%
Week 1 Number Analyzed 25 participants 9 participants
23
  92.0%
6
  66.7%
EOT Number Analyzed 23 participants 9 participants
20
  87.0%
6
  66.7%
EOS Number Analyzed 18 participants 3 participants
16
  88.9%
3
 100.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.353
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments At Day 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.401
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments At Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments At week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.102
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.314
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
Hide Description 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.
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)
Hide Outcome Measure Data
Hide Analysis Population Description

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.

Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 8 participants 5 participants
56.9  (37.3) 4.0  (5.5)
to Day 1 Number Analyzed 4 participants 4 participants
4.3  (8.5) 20.0  (40.0)
to Day 2 Number Analyzed 4 participants 4 participants
32.3  (40.3) 44.8  (51.7)
Week 1 Number Analyzed 5 participants 3 participants
29.0  (34.0) 86.0  (5.3)
EOT Number Analyzed 5 participants 3 participants
33.0  (41.8) 89.7  (0.6)
EOS Number Analyzed 2 participants 0 participants
22.5  (31.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change of VAS scale.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change of VAS scale.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments week 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change of VAS scale.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0227
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change of VAS scale.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
Hide Description

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.

Time Frame Baseline, Day 1, Day 2, Week 1, EOT and EOS
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: F°
Baseline Number Analyzed 36 participants 19 participants
36.4  (0.5) 36.5  (0.5)
to Day 1 Number Analyzed 34 participants 19 participants
-0.2  (0.5) 0.2  (0.9)
to Day 2 Number Analyzed 35 participants 18 participants
-0.1  (0.7) -0.1  (0.6)
to Week 1 Number Analyzed 32 participants 14 participants
-0.1  (0.6) -0.2  (0.6)
to EOT Number Analyzed 32 participants 15 participants
-0.2  (0.6) -0.4  (0.6)
to EOS Number Analyzed 10 participants 3 participants
-0.1  (0.5) -0.5  (0.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments At Day 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.122
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments At Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.985
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.857
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments at EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.436
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments At EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.350
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
Hide Description

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.

Time Frame At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of subjects
Day 1 - subjects worsened (%) Number Analyzed 27 participants 14 participants
7.4
(0.9 to 24.3)
14.3
(1.8 to 42.8)
Day 2 - subjects worsened (%) Number Analyzed 31 participants 15 participants
12.9
(3.6 to 29.8)
20.0
(4.3 to 48.1)
Week 1 - subjects worsened (%) Number Analyzed 26 participants 14 participants
0.0
(0.0 to 13.2)
21.4
(4.7 to 50.8)
EOT - subjects worsened (%) Number Analyzed 29 participants 12 participants
0.0
(0.0 to 11.9)
8.3
(0.2 to 38.5)
EOS - subjects worsened (%) Number Analyzed 10 participants 3 participants
0.0
(0.0 to 30.8)
0.0
(0.0 to 70.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1
Type of Statistical Test Superiority
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Statistical Test of Hypothesis P-Value 0.596
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2
Type of Statistical Test Superiority
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Statistical Test of Hypothesis P-Value 0.667
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Statistical Test of Hypothesis P-Value 0.293
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
Hide Description 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).
Time Frame day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
Day 1 - subjects worsened Number Analyzed 36 participants 19 participants
5.6
(0.7 to 18.7)
0.0
(0.0 to 17.6)
Day 2 - subjects worsened Number Analyzed 36 participants 19 participants
5.6
(0.7 to 18.7)
5.3
(0.1 to 26.0)
Week 1 - subjects worsened Number Analyzed 34 participants 17 participants
2.9
(0.1 to 15.3)
17.6
(3.8 to 43.4)
EOT - subjects worsened Number Analyzed 35 participants 19 participants
2.9
(0.1 to 14.9)
15.8
(3.4 to 39.6)
EOS - subjects worsened Number Analyzed 28 participants 12 participants
3.6
(0.1 to 18.3)
8.3
(0.2 to 38.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.539
Comments p-values are referred to a two-sided Fisher's Exact test for worsening and
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.102
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.119
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.515
Comments p-values are referred to a two-sided Fisher's Exact test for worsening
Method Fisher Exact
Comments [Not Specified]
8.Secondary Outcome
Title Phase 2 - Oxygen Cumulative Duration During the Study
Hide Description 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.
Time Frame Week 1, EOT, EOS
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: hours
week 1 Number Analyzed 34 participants 18 participants
141.93  (55.68) 130.22  (80.89)
EOT Number Analyzed 34 participants 18 participants
151.55  (75.53) 134.00  (86.21)
EOS Number Analyzed 36 participants 18 participants
195.26  (198.62) 155.71  (135.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.366
Comments p-values are referred to a two-sided Wilcoxon test for cumulative duration.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.489
Comments p-values are referred to a two-sided Wilcoxon test for cumulative duration.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.486
Comments p-values are referred to a two-sided Wilcoxon test for cumulative duration.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title Phase 2 - Oxygen Cumulative Quantity During the Study
Hide Description

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.

Time Frame Week 1, EOT and EOS
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: liters
Week 1 Number Analyzed 33 participants 18 participants
24.99  (22.22) 29.20  (29.51)
EOT Number Analyzed 33 participants 18 participants
25.64  (22.16) 29.73  (31.53)
EOS Number Analyzed 35 participants 18 participants
26.54  (22.31) 33.38  (31.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.790
Comments p-values are referred to a two-sided Wilcoxon test for cumulative quantity
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.961
Comments p-values are referred to a two-sided Wilcoxon test for cumulative quantity
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.619
Comments p-values are referred to a two-sided Wilcoxon test for cumulative quantity
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
Hide Description 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.
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
Baseline - subjects requiring Number Analyzed 36 participants 19 participants
11.1
(3.1 to 26.1)
10.5
(1.3 to 33.1)
Day1 - subjects requiring Number Analyzed 36 participants 19 participants
11.1
(3.1 to 26.1)
10.5
(1.3 to 33.1)
Day 2 - subjects requiring Number Analyzed 35 participants 18 participants
11.4
(3.2 to 26.7)
16.7
(3.6 to 41.4)
Week 1- subjects requiring Number Analyzed 34 participants 17 participants
8.8
(1.9 to 23.7)
11.8
(1.5 to 36.4)
EOT - subjects requiring Number Analyzed 35 participants 19 participants
8.6
(1.8 to 23.1)
5.3
(0.1 to 26.0)
EOS -subjects requiring Number Analyzed 27 participants 10 participants
0.0
(0.0 to 12.8)
0.0
(0.0 to 30.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS)
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.678
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
11.Secondary Outcome
Title Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall
Hide Description

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

Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: hours
Week 1 Number Analyzed 4 participants 3 participants
162.54  (58.92) 142.42  (44.89)
EOT Number Analyzed 4 participants 3 participants
149.99  (53.23) 146.86  (43.80)
EOS Number Analyzed 4 participants 3 participants
179.51  (78.30) 154.86  (56.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.696
Comments p-values are referred to a two-sided Wilcoxon test for cumulative duration
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments p-values are referred to a-sided Wilcoxon test for cumulative duration
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.596
Comments p-values are referred to a-sided Wilcoxon test for cumulative duration
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
12.Secondary Outcome
Title Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
Hide Description 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.
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
Baseline - subjects admitted to ICU Number Analyzed 36 participants 19 participants
2.8
(0.1 to 14.5)
5.3
(0.1 to 26.0)
Day 1 - subjects admitted to ICU Number Analyzed 36 participants 19 participants
2.8
(0.1 to 14.5)
5.3
(0.1 to 26.0)
Day 2 - subjects admitted to ICU Number Analyzed 35 participants 18 participants
5.7
(0.7 to 19.2)
5.6
(0.1 to 27.3)
Week 1 - subjects admitted to ICU Number Analyzed 34 participants 17 participants
2.9
(0.1 to 15.3)
0.0
(0.0 to 19.5)
EOT - subjects admitted to ICU Number Analyzed 35 participants 19 participants
2.9
(0.1 to 14.9)
0.0
(0.0 to 17.6)
EOS - subjects admitted to ICU Number Analyzed 27 participants 10 participants
0.0
(0.0 to 30.8)
0.0
(0.0 to 12.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Fisher Exact
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments p-values are referred to a two-sided Fisher's Exact test for proportion
Method Fisher Exact
Comments [Not Specified]
13.Secondary Outcome
Title Phase 2 - Cumulative ICU Stay
Hide Description Cumulative ICU stay was assessed at different timepoints and measured in days
Time Frame Day 1, Day 2, Week 1, EOT, EOS
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Median (Full Range)
Unit of Measure: days
Day 1 - cumulative ICU stay Number Analyzed 1 participants 1 participants
1.0
(1 to 1)
1.0
(1 to 1)
Day 2 - cumulative ICU stay Number Analyzed 1 participants 1 participants
2.0
(2 to 2)
2.0
(2 to 2)
Week 1 - cumulative ICU stay Number Analyzed 1 participants 1 participants
7.0
(7 to 7)
3.0
(3 to 3)
EOT - cumulative ICU stay Number Analyzed 1 participants 1 participants
6.0
(6 to 6)
3.0
(3 to 3)
EOS - cumulative ICU stay Number Analyzed 36 participants 1 participants
50.0
(50 to 50)
3.0
(3 to 3)
14.Secondary Outcome
Title Phase 2 - Lung Damage Extension by Severity and by Timepoint
Hide Description

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.

Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Unit of Measure: participants
baseline - none Number Analyzed 36 participants 19 participants
0 0
baseline - trace Number Analyzed 36 participants 19 participants
1 2
baseline - mild Number Analyzed 36 participants 19 participants
9 3
baseline - moderate Number Analyzed 36 participants 19 participants
23 11
baseline - severe Number Analyzed 36 participants 19 participants
3 3
Day 1 - none Number Analyzed 1 participants 1 participants
0 0
Day 1 - trace Number Analyzed 1 participants 1 participants
0 0
Day 1 - mild Number Analyzed 1 participants 1 participants
0 1
Day 1 - moderate Number Analyzed 1 participants 1 participants
1 0
Day 1 - severe Number Analyzed 1 participants 1 participants
0 0
Day 2 - none Number Analyzed 1 participants 1 participants
0 0
Day 2 - trace Number Analyzed 1 participants 1 participants
0 0
Day 2 - mild Number Analyzed 1 participants 1 participants
0 1
Day 2 - moderate Number Analyzed 1 participants 1 participants
0 0
Day 2 - severe Number Analyzed 1 participants 1 participants
1 0
week 1 - none Number Analyzed 12 participants 4 participants
0 0
week 1- trace Number Analyzed 12 participants 4 participants
1 0
week 1 - mild Number Analyzed 12 participants 4 participants
6 2
week 1 - moderate Number Analyzed 12 participants 4 participants
4 0
week 1 - severe Number Analyzed 12 participants 4 participants
1 2
EOT - none Number Analyzed 16 participants 19 participants
1 0
EOT - trace Number Analyzed 16 participants 19 participants
3 0
EOT - mild Number Analyzed 16 participants 19 participants
8 2
EOT - moderate Number Analyzed 16 participants 19 participants
3 0
EOT - severe Number Analyzed 16 participants 19 participants
1 2
EOS - none Number Analyzed 2 participants 19 participants
0 0
EOS - trace Number Analyzed 2 participants 19 participants
0 0
EOS - mild Number Analyzed 2 participants 19 participants
1 1
EOS - moderate Number Analyzed 2 participants 19 participants
1 1
EOS - severe Number Analyzed 2 participants 19 participants
0 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.760
Comments p-values are referred to a two-sided Wilcoxon test
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.394
Comments p-values are referred to a two-sided Wilcoxon test
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.141
Comments p-values are referred to a two-sided Wilcoxon test
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments p-values are referred to a two-sided Wilcoxon test
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
15.Secondary Outcome
Title Phase 2 - Lung Exudation by Severity and by Timepoint
Hide Description

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.

Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Measure Type: Number
Unit of Measure: participants
baseline - none Number Analyzed 36 participants 19 participants
32 18
baseline - trace Number Analyzed 36 participants 19 participants
0 0
baseline - mild Number Analyzed 36 participants 19 participants
1 0
baseline - moderate Number Analyzed 36 participants 19 participants
3 1
baseline - severe Number Analyzed 36 participants 19 participants
0 0
Day 1 - none Number Analyzed 1 participants 1 participants
0 0
Day 1 - trace Number Analyzed 1 participants 1 participants
0 0
Day 1 - mild Number Analyzed 1 participants 1 participants
0 0
Day 1 - moderate Number Analyzed 1 participants 1 participants
1 1
Day 1 - severe Number Analyzed 1 participants 1 participants
0 0
Day 2 - none Number Analyzed 1 participants 1 participants
0 0
Day 2 - trace Number Analyzed 1 participants 1 participants
0 0
Day 2 - mild Number Analyzed 1 participants 1 participants
0 1
Day 2 - moderate Number Analyzed 1 participants 1 participants
0 0
Day 2 - severe Number Analyzed 1 participants 1 participants
1 0
week 1 - none Number Analyzed 12 participants 4 participants
12 3
week 1- trace Number Analyzed 12 participants 4 participants
0 0
week 1 - mild Number Analyzed 12 participants 4 participants
0 0
week 1 - moderate Number Analyzed 12 participants 4 participants
0 0
week 1 - severe Number Analyzed 36 participants 4 participants
12 1
EOT - none Number Analyzed 16 participants 4 participants
15 3
EOT - trace Number Analyzed 16 participants 4 participants
0 0
EOT - mild Number Analyzed 16 participants 4 participants
1 0
EOT - moderate Number Analyzed 16 participants 19 participants
0 4
EOT - severe Number Analyzed 16 participants 4 participants
0 0
EOS - none Number Analyzed 2 participants 2 participants
2 2
EOS - trace Number Analyzed 2 participants 2 participants
0 0
EOS - mild Number Analyzed 2 participants 2 participants
0 0
EOS - moderate Number Analyzed 2 participants 2 participants
0 0
EOS - severe Number Analyzed 2 participants 2 participants
0 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.500
Comments p-values are referred to a two-sided Wilcoxon test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.112
Comments p-values are referred to a two-sided Wilcoxon test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.277
Comments p-values are referred to a two-sided Wilcoxon test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments p-values are referred to a two-sided Wilcoxon test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Secondary Outcome
Title Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
Hide Description

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.

Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline Number Analyzed 17 participants 8 participants
121.69  (47.15) 68.64  (9.23)
to Day 1 Number Analyzed 8 participants 4 participants
-19.61  (50.09) 14.20  (25.76)
to Day 2 Number Analyzed 13 participants 4 participants
12.62  (60.20) -4.68  (14.03)
to week 1 Number Analyzed 10 participants 3 participants
11.76  (25.26) -1.13  (54.80)
to EOT Number Analyzed 11 participants 1 participants
8.01  (36.08) -18.70
to EOS Number Analyzed 8 participants 1 participants
-35.76  (47.84) 1.80
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2027
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Week 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4469
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2466
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1752
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
17.Secondary Outcome
Title Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
Hide Description 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.
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: percent of oxygen saturation
Baseline Number Analyzed 35 participants 18 participants
95.79  (3.17) 94.97  (2.60)
to Day 1 Number Analyzed 29 participants 18 participants
0.17  (2.20) -0.41  (3.57)
to Day 2 Number Analyzed 32 participants 17 participants
0.38  (2.88) -0.63  (3.86)
to week 1 Number Analyzed 30 participants 13 participants
1.18  (3.34) 0.73  (3.71)
to EOT Number Analyzed 29 participants 14 participants
0.88  (3.57) 1.19  (3.89)
to EOS Number Analyzed 10 participants 2 participants
0.47  (3.17) -4.00  (1.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6441
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3529
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments week 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3581
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1666
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0851
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
18.Secondary Outcome
Title Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
Hide Description 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).
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: ratio
Baseline Number Analyzed 34 participants 17 participants
186.82  (64.86) 196.91  (58.49)
To day 1 Number Analyzed 27 participants 14 participants
21.58  (65.81) 6.08  (125.00)
To day 2 Number Analyzed 31 participants 15 participants
48.29  (154.49) -8.53  (71.74)
To week 1 Number Analyzed 26 participants 14 participants
160.80  (137.83) 54.28  (138.36)
To EOT Number Analyzed 29 participants 12 participants
171.27  (149.56) 74.65  (113.55)
To EOS Number Analyzed 10 participants 3 participants
199.26  (85.45) 84.87  (67.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3359
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3136
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments week 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0441
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0965
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0519
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
19.Secondary Outcome
Title Phase 2 - Change From Baseline in Reactive Protein (CRP)
Hide Description 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.
Time Frame Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
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;
Arm/Group Title Reparixin (FAS) Standard of Care (FAS)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: mg/L
baseline Number Analyzed 35 participants 19 participants
57.04  (41.44) 58.87  (57.25)
to day 1 Number Analyzed 11 participants 9 participants
-0.14  (73.28) 38.46  (117.19)
to day 2 Number Analyzed 22 participants 8 participants
-29.24  (37.66) -2.15  (52.37)
to week 1 Number Analyzed 26 participants 14 participants
-39.09  (56.56) 0.52  (80.24)
to EOT Number Analyzed 24 participants 13 participants
-40.88  (50.27) -25.28  (87.16)
to EOS Number Analyzed 11 participants 7 participants
-49.43  (57.65) -45.20  (78.97)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.470
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments Day 2 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.425
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments week 1 vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOT vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.600
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Reparixin (FAS), Standard of Care (FAS)
Comments EOS vs baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.717
Comments p-values are referred to a two-sided Wilcoxon test for differences in the change.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Throughout the study, till day 21
Adverse Event Reporting Description The Safety set (SAF), which consisted of all randomized subjects who received at least one dose of the investigational medicinal product (IMP).
 
Arm/Group Title Reparixin (SAF) Standard of Care (SAF)
Hide Arm/Group Description 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, which is defined as any drug currently used to treat the COVID-19 pneumonia.
All-Cause Mortality
Reparixin (SAF) Standard of Care (SAF)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/36 (2.78%)      3/19 (15.79%)    
Hide Serious Adverse Events
Reparixin (SAF) Standard of Care (SAF)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/36 (2.78%)      1/19 (5.26%)    
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/36 (2.78%)  1 1/19 (5.26%)  1
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Reparixin (SAF) Standard of Care (SAF)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/36 (2.78%)      1/19 (5.26%)    
Gastrointestinal disorders     
Diarrhoea  1  1/36 (2.78%)  1 1/19 (5.26%)  1
Injury, poisoning and procedural complications     
Post procedural discomfort  1  0/36 (0.00%)  0 1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/36 (2.78%)  1 1/19 (5.26%)  1
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Maria De Pizzol, BSc
Organization: Dompé Farmaceutici
Phone: +39 02 583831
EMail: clinops@pec.dompe.it
Layout table for additonal information
Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT04794803    
Other Study ID Numbers: REPAVID-19
2020-001645-40 ( EudraCT Number )
First Submitted: March 8, 2021
First Posted: March 12, 2021
Results First Submitted: February 21, 2022
Results First Posted: March 17, 2022
Last Update Posted: May 24, 2022