A Phase 3 interventional study of Reparixin and Placebo in Infectious Pneumonia and Severe COVID-19, sponsored by Dompé Farmaceutici S.p.A. Terminated at 74 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-24.
Sponsored by Dompé Farmaceutici S.p.A · Phase 3, Interventional, and Treatment
Primary objective:
- To compare the efficacy of reparixin vs. placebo in the proportion of patients dead or requiring IMV (or ECMO) by Day 28.
Key secondary objectives:
Other efficacy objectives
- To compare the efficacy of reparixin vs placebo on several disease severity/progression measures including recovery, ventilatory free days and mortality.
Safety objectives:
- To evaluate safety and tolerability of oral reparixin versus placebo in the specific clinical setting.
Multinational, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III trial.
This study was conducted at 101 sites across 7 countries (Argentina, Australia, Austria, Germany, Italy, Turkey, and the United States [US]) that enrolled 414 male and female patients > 18 years of age, hospitalized for CAP (including COVID-19). Please note that of these 101 sites, only 74 had enrolled patients and, hence, have been reported on CT.gov.
The maximum study duration for a participant was 180 days, which included screening (day -1 or 1), treatment (up to day 21), and follow-up period (up to day 180).
Of the 414 patients enrolled, 409 (98.8%) were randomized 1:1 to receive investigational products (oral reparixin [N = 205] or matched placebo [N = 204], three times a day (TID), for up to 21 days. Randomization was stratified according to disease severity and site.
Actually, 394 participants (96.3%)(oral reparixin [N = 201] or matched placebo [N = 193]) received at least 1 dose of the investigational product and hence were included in the FAS population.
All the patients received the Standard of Care (SoC) based on their clinical need, including COVID-19 and CAP medications, as per local standard therapy at the trial site and in line with international guidelines.
Of the randomized population (N = 409), 186 participants (45.5%) completed the study; 223 (54.5%) discontinued the study prematurely.
The primary outcome was evaluated at day 28, while the secondary outcomes were scheduled to be evaluated from day 3 to day 180.
An independent external data monitoring committee (DMC) oversaw the study and evaluated unblinded interim data for efficacy, futility, and safety.
The interim efficacy analysis met the pre-specified criteria for futility and the DMC recommended early termination of the study. Based on the recommendation of the DMC, Dompé decided to terminate the study earlier than planned. The decision was not related to any safety concerns.
Due to the early study termination and not reaching the planned enrollment target, the outcome measure analyses were conducted for descriptive purposes only.
7,990 studies on the registry are indexed under COVID-19; 466 are open to participants now.
This study's enrollment of 414 is above the median of 102 across 4,364 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Dompé Farmaceutici S.p.A is the lead sponsor of 52 studies on the registry; 4 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 18 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients hospitalized for clinically suspected CAP, defined as the occurrence of (within 48h from hospital admission):
Females of and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of :
Female participants of non-child-bearing potential or in status for at least 1 year will be admitted. For all female subjects, with child-bearing potential, pregnancy test result must be negative before first drug intake.
Exclusion Criteria:
History of:
Pregnancy:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reparixin was administered orally at the dose of 1200 mg (2 x 600 mg tablets) TID (6 tablets daily) for up to 21 days. The three daily doses were administered maintaining an interval between doses of about 8 hours.
Drug: Reparixin
Placebo tablets are identical in appearance to the active formulation. Placebo was administered with the same treatment schedule.
Other: Placebo
Reparixin 600 mg tablets, administered orally at the dose of 1200 mg TID (2 tablets TID) as add-on therapy to standard of care up to 21 days. IMP was taken with a glass of water (about 250 mL) and a light meal or snack, as it was preferable that reparixin was taken with food. However, If the patient was unwilling or unable to administer oral tablets, investigator could decide a nasogastric tube as an alternative route.
Also known as: Repertaxin L-lysine salt
Administered orally three times a day (TID) as add-on therapy to standard of care (SoC) up to 21 days. Placebo was taken with a glass of water (about 250 mL) and a light meal or snack, as it was preferable that placebo was taken with food. However, if the patient was unwilling or unable to administer oral tablets, investigator could decide a nasogastric tube as an alternative route.
Also known as: Matched placebo
Proportion of Patients Dead or Requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 [NIAID-OS 7].
The primary endpoint was based on NIAID-OS ordinal scale (National Institute of Allergy and Infectious Disease) with score OS 7 which means patients "hospitalized, on invasive mechanical ventilation or ECMO". The scores on this scale of Disease severity range from OS 1 (best outcome) to OS 8 (worst outcome). NIAID-OS (National Institute of Allergy and Infectious Disease Ordinal Scale) SCORE Descriptor: * OS 1 Not hospitalized, no limitations on activities; * OS 2 Not hospitalized, limitation on activities and/or requiring home O2; * OS 3 Hospitalized, no supplemental O2 - no longer requires ongoing medical care; * OS 4 Hospitalized, no supplemental O2 - requiring ongoing medical care; * OS 5 Hospitalized, requiring supplemental O2; * OS 6 Hospitalized, on non-invasive ventilation or high-flow oxygen devices; * OS 7 Hospitalized, on invasive mechanical ventilation or ECMO; * OS 8 Death;
Time frame: Day 28
All-cause Mortality by Day 180
Key secondary endpoint. All-cause mortality is a measurement of the total number of deaths from any cause within a specific population over a defined period. It is a broad metric used in medical research and public health to assess overall population health, identify risk factors for premature death, and evaluate the effectiveness of interventions. The number of participants (in the form of unadjusted proportion) who met the endpoint is reported.
Time frame: Day 180
Proportion of Patients Alive and Discharged From the Hospital by Day 28
Key secondary endpoint. The number of participants alive or discharged, expressed in the form of unadjusted proportion, who met the endpoint at the final analysis at day 28 is provided.
Time frame: Day 28
Ventilatory-free Days (VFD) by Day 28
Key secondary endpoint. Number of days from Day 0 to Day 28 when the patient was alive and free of invasive ventilation is reported. In case of multiple periods of IMV during the first 28 days, the total duration of ventilation considered all periods of ventilation during the index admission. Patients who died within 28 days or who still were on invasive ventilation after 28 days were scored 0 VFDs.
Time frame: Day 28
Proportion of Patients With IMV (or ECMO) by Day 28
Key secondary endpoint.The number of participants, expressed in the form of unadjusted proportion, who met the endpoint at the final analysis is reported.
Time frame: Day 28
Length of Primary Hospital Stay (in Days)
Key secondary endpoint. The duration of primary hospital stay, expressed in days, are reported. This parameter is included in the set of final evaluation, which comprises: no. of days of hospitalization, etiologic agents (if identified), ICU admission and total days in ICU, occurrence, and duration of IMV and/or ECMO, if any.
Time frame: Day 180
Clinical Failure by Day 3 and Day 7
Clinical failure was defined as the occurrence of IMV/ECMO or vasopressor, or death. IMV= invasive mechanical ventilation. ECMO=extracorporeal membrane oxygenation.
Time frame: Day 3 and Day 7
28-day ICU-free Days
ICU-free days = days of hospitalization out of the Intensive Care Unit. Death within Day 28 was handled as an unfavorable event and ICU-free days were set at 0.
Time frame: Day 28
Days Free of IMV or ECMO (Number of Days With NIAID-OS 1-6) by Day 28
These parameters are expressed as number of days with NIAID-OS score not equal to 7 or 8, where NIAID-OS is the National Institute of Allergy and Infectious Disease Ordinal Scale; a scale ranging from 1 to 8, where the lower the score, the better the outcome. The IMV/ECMO-free days at Day 28 were analyzed according to MI approach and ANOVA model. Death due to progression of the respiratory disease within Day 28 was handled as an unfavorable event and IMV/ECMO-free days at Day 28 was set at 0.
Time frame: Day 28
Duration of Antibiotic Therapy (Days) by Day 28
A descriptive summary of duration of antibiotic therapy (days) at day 28 for the FAS is reported.
Time frame: Day 28
Hospital Free Days
Results for hospital-free days at day 28 in the FAS are presented through an unadjusted descriptive summary.
Time frame: Day 28
Proportion of Patients Recovered
Results for the proportion of participants recovered at fixed timepoints in the FAS are presented. Recovering was defined as a downward shift from screening of ≤2 points on the NIAID-OS or live discharge from hospital. Unadjusted proportion is reported.
Time frame: days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41)
Proportion of Patients Worsening
Results for the proportion of participants worsening at fixed timepoints in the FAS are presented. Worsening was expressed as upward shift from screening of at least \>1 point of the NIAID-OS or if patient died before X Visit Day. An unadjusted proportion is reported.
Time frame: days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41)
Change From Baseline in the Arterial Partial Pressure of Oxygen (PaO2)
Descriptive statistics for the change from baseline in arterial partial pressure of oxygen (PaO2) at fixed timepoints are reported.
Time frame: days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41)
Change From Baseline in Pulse Oximetry (SpO2)
Descriptive statistics for the change from baseline in pulse oximetry, measured as peripheral arterial oxygen saturation (SpO2), at fixed timepoints are reported.
Time frame: days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41)
Change From Baseline in Inspired Oxygen (FiO2) Levels
FiO2 is a parameter of lung function representing the fraction of oxygen in the inspired air, ranging from 0.21 (room air) to 1.00 (100% oxygen). The endpoint assesses the change from baseline in FiO2 levels at predefined timepoints during the study.
Time frame: days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41)
Change From Baseline in PaO2/FiO2 Ratio
The PaO2/FiO2 ratio is a parameter of lung function that reflects the efficiency of oxygen transfer from the lungs to the blood. It is calculated as the ratio between the arterial partial pressure of oxygen (PaO2, measured in mmHg) and the fraction of inspired oxygen (FiO2, expressed as a fraction ranging from 0.21 to 1.00). This endpoint assesses the change from baseline in the PaO2/FiO2 ratio at predefined timepoints during the study.
Time frame: days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41)
Change From Baseline in SpO2/FiO2 Ratio
The SpO2/FiO2 ratio is a noninvasive indicator of lung function and oxygenation efficiency, calculated as the ratio between peripheral oxygen saturation (SpO2, expressed as a percentage) and the fraction of inspired oxygen (FiO2, expressed as a fraction ranging from 0.21 to 1.00). This endpoint assesses the change from baseline in the SpO2/FiO2 ratio at predefined timepoints during the study.
Time frame: Days 3, 7, 14, 21, and 28
All-cause Mortality
Results for all-cause mortality rates in the FAS are reported, at day 28, day 60, and day 90. Analysis was based on logistic regression model with Multiple Imputation using retrieve dropouts with proportion of patients died up to Day 28 as dependent variable, treatment, disease severity at baseline (NIAID-OS \<=5 vs. NIAID-OS 6), age class (\<65, \>= 65 years), sex and presence of concomitant disease at baseline as qualitative independent variables.
Time frame: Days 28, 60 and 90
Hospital Re-admission by Day 90 and 180
Hospital Re-admission by Day 90 and 180 in the FAS is presented. The number of participants is expressed as unadjusted proportion.
Time frame: Days 90 and 180
Time to Discharge or to a NEWS (National Early Warning Score) of ≤ 2 (for 24 Hours), Whichever Occurs First
The median time to discharge or to a NEWS (National Early Warning Score) of ≤ 2 (for 24 hours), whichever occurs first, was expressed using a "time to event" approach, and measured in days. NIAID-OS, National Early Warning Score (NEWS) was evaluated daily until day 28 (or hospital discharge). In a scored system standardizing the assessment of acute-illness severity in the NHS, NEWS includes Blood Pressure (BP), Heart Rate (HR), Respiratory Rate (RR), body temperature, level of consciousness (A, V, P, U), peripheral arterial oxygen saturation (SpO2) and supplemental oxygen. Time to discharge or to a NEWS of \<= 2 (for 24 hours) = Min(Date of discharge, Date of NEWS of \<= 2 (for 24 hours)) - Day 1 date + 1. Date of NEWS of \<= 2 (for 24 hours): Given two consecutive days with NEWS of \<= 2, the date of the first assessment has been considered.
Time frame: Day 28
Change in Quality of Life Using EuroQol-5-dimensions-5 Levels (EQ-5D-5L) Questionnaire From Hospital Discharge to Day 90 and Day 180
The EQ-5D-5L asks patients to indicate whether they have no, slight, moderate, severe, extreme problems on each of 5 dimensions of health: mobility; self-care; usual activities; pain/discomfort; anxiety/depression.The count of patients of each level (1 - no problems, 2 - slight problems, 3 - moderate problems, 4 - severe problems, 5 - extreme problems) for each of the 5 dimensions were reported. The higher the score for each dimension (range 1-5), the worse the outcome.
Time frame: Days 90±7 and 180±14
Duration of IMV and/or ECMO by Days 90 and 180
The summary of IMV/ECMO duration by day 90 and day 180 for the FAS is presented. The duration of IMV/ECMO use by day 90 was calculated as the total number of days between day 1 and the last available assessment day (≥ day 83) during which the participant was either receiving IMV/ECMO or had a NIAID-OS score of 7. Participants with less than 83 days of follow-up were considered non-evaluable for this endpoint. Similarly, the duration of IMV/ECMO by day 180 was calculated using the same methodology.
Time frame: Days 90 and 180
Proportion of Participants Requiring ICU Admission by Days 90 and 180
Unadjusted proportion of ICU admission is reported as number and percentage of participants requiring ICU admission by day 90 and day 180.
Time frame: Days 90 and 180
ICU Length of Stay by Days 90 and 180
Results for the Intensive Care Unit length of stay (days) by day 90 and day 180 in the FAS are reported.
Time frame: Days 90 and 180
Hospital Length of Stay by Days 90 and 180
Results for hospital length of stay (days) by day 90 and 180 in the FAS are reported.
Time frame: Days 90 and 180
Occurrence of Infections by Days 90 and 180
Occurrence of infections was expressed as the unadjusted proportion of participants with at least one infection by days 90 and 180 in the FAS.
Time frame: Days 90 and 180
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE)
A TEAE is defined as any adverse event reported in the study having a possible, probable, or highly probable relationship to investigational product. A serious AE is defined as any untoward medical occurrence that at any dose: * results in death. * is life-threatening (i.e. the patient was at risk of death at the time of the event. It does not refer to an event which hypothetically might have caused death if it were more severe), * requires inpatient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect * is a medically significant or important medical condition, i.e. an important medical event that based upon appropriate medical judgment, may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Throughout the study till Day 180 (± 14) or end of treatment
A total of 444 participants were screened and 414 were enrolled; 409 (98.8%) were randomized 1:1 to receive investigational products (reparixin \[N = 205\] or placebo \[N = 204\]). A total of 186 participants (45.5%) completed the study; 223 (54.5%) discontinued the study prematurely.
| Milestone | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Started | 205 | 204 |
| Fas population | 201 | 193 |
| Saf population | 201 | 193 |
| Pp population | 139 | 133 |
| Completed | 90 | 96 |
| Not completed | 115 | 108 |
| Withdrew: Sponsor's decision to terminate the study early | 53 | 43 |
| Withdrew: Death | 16 | 19 |
| Withdrew: Lost to follow-up | 24 | 22 |
| Withdrew: Withdrawal by subject | 17 | 10 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Physician decision | 2 | 4 |
| Withdrew: Other | 2 | 9 |
The primary endpoint was based on NIAID-OS ordinal scale (National Institute of Allergy and Infectious Disease) with score OS 7 which means patients "hospitalized, on invasive mechanical ventilation or ECMO". The scores on this scale of Disease severity range from OS 1 (best outcome) to OS 8 (worst outcome). NIAID-OS (National Institute of Allergy and Infectious Disease Ordinal Scale) SCORE Descriptor: * OS 1 Not hospitalized, no limitations on activities; * OS 2 Not hospitalized, limitation on activities and/or requiring home O2; * OS 3 Hospitalized, no supplemental O2 - no longer requires ongoing medical care; * OS 4 Hospitalized, no supplemental O2 - requiring ongoing medical care; * OS 5 Hospitalized, requiring supplemental O2; * OS 6 Hospitalized, on non-invasive ventilation or high-flow oxygen devices; * OS 7 Hospitalized, on invasive mechanical ventilation or ECMO; * OS 8 Death;
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Proportion of Patients Dead or Requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 [NIAID-OS 7]. | 7 | 12 |
Key secondary endpoint. All-cause mortality is a measurement of the total number of deaths from any cause within a specific population over a defined period. It is a broad metric used in medical research and public health to assess overall population health, identify risk factors for premature death, and evaluate the effectiveness of interventions. The number of participants (in the form of unadjusted proportion) who met the endpoint is reported.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| All-cause Mortality by Day 180 | 16 | 18 |
Key secondary endpoint. The number of participants alive or discharged, expressed in the form of unadjusted proportion, who met the endpoint at the final analysis at day 28 is provided.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Proportion of Patients Alive and Discharged From the Hospital by Day 28 | 170 | 159 |
Key secondary endpoint. Number of days from Day 0 to Day 28 when the patient was alive and free of invasive ventilation is reported. In case of multiple periods of IMV during the first 28 days, the total duration of ventilation considered all periods of ventilation during the index admission. Patients who died within 28 days or who still were on invasive ventilation after 28 days were scored 0 VFDs.
| number of days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Ventilatory-free Days (VFD) by Day 28 | 27.4 ± 4.2 | 26.5 ± 6.3 |
Key secondary endpoint.The number of participants, expressed in the form of unadjusted proportion, who met the endpoint at the final analysis is reported.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Proportion of Patients With IMV (or ECMO) by Day 28 | 6 | 10 |
Key secondary endpoint. The duration of primary hospital stay, expressed in days, are reported. This parameter is included in the set of final evaluation, which comprises: no. of days of hospitalization, etiologic agents (if identified), ICU admission and total days in ICU, occurrence, and duration of IMV and/or ECMO, if any.
| days of hospital stay | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Length of Primary Hospital Stay (in Days) | 8.7 ± 6.3 | 8.7 ± 7.0 |
Clinical failure was defined as the occurrence of IMV/ECMO or vasopressor, or death. IMV= invasive mechanical ventilation. ECMO=extracorporeal membrane oxygenation.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 3 | 2 | 7 |
| Day 7 | 5 | 9 |
ICU-free days = days of hospitalization out of the Intensive Care Unit. Death within Day 28 was handled as an unfavorable event and ICU-free days were set at 0.
| days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| 28-day ICU-free Days | 26.3 ± 5.0 | 25.7 ± 6.8 |
These parameters are expressed as number of days with NIAID-OS score not equal to 7 or 8, where NIAID-OS is the National Institute of Allergy and Infectious Disease Ordinal Scale; a scale ranging from 1 to 8, where the lower the score, the better the outcome. The IMV/ECMO-free days at Day 28 were analyzed according to MI approach and ANOVA model. Death due to progression of the respiratory disease within Day 28 was handled as an unfavorable event and IMV/ECMO-free days at Day 28 was set at 0.
| days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Days Free of IMV or ECMO (Number of Days With NIAID-OS 1-6) by Day 28 | 27.4 ± 4.2 | 26.8 ± 5.6 |
A descriptive summary of duration of antibiotic therapy (days) at day 28 for the FAS is reported.
| days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Duration of Antibiotic Therapy (Days) by Day 28 | 9.6 ± 8.3 | 9.2 ± 8.6 |
Results for hospital-free days at day 28 in the FAS are presented through an unadjusted descriptive summary.
| days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Hospital Free Days | 18.3 ± 6.7 | 18.2 ± 7.6 |
Results for the proportion of participants recovered at fixed timepoints in the FAS are presented. Recovering was defined as a downward shift from screening of ≤2 points on the NIAID-OS or live discharge from hospital. Unadjusted proportion is reported.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 3 | 11 | 15 |
| Day 7 | 40 | 49 |
| Day 14 | 138 | 135 |
| Day 21 | 31 | 24 |
| Day 28 | 151 | 139 |
| Hospital discharge (Up to Day 41) | 146 | 145 |
Results for the proportion of participants worsening at fixed timepoints in the FAS are presented. Worsening was expressed as upward shift from screening of at least \>1 point of the NIAID-OS or if patient died before X Visit Day. An unadjusted proportion is reported.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 3 | 6 | 10 |
| Day 7 | 4 | 6 |
| Day 14 | 2 | 6 |
| Day 21 | 3 | 7 |
| Day 28 | 5 | 10 |
| Hospital discharge (Up to Day 41) | 5 | 4 |
Descriptive statistics for the change from baseline in arterial partial pressure of oxygen (PaO2) at fixed timepoints are reported.
| mmHg | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| To day 3 | 15.80 ± 27.96 | 9.08 ± 22.18 |
| To day 7 | 15.44 ± 29.50 | 11.10 ± 27.94 |
| To day 14 | 20.09 ± 30.42 | 18.28 ± 20.62 |
| To day 21 | 8.63 ± 37.04 | 21.88 ± 26.43 |
| To day 28 | 23.65 ± 30.02 | 25.98 ± 21.54 |
| Hospital discharge (Up to Day 41) | 25.45 ± 17.57 | 24.52 ± 6.20 |
Descriptive statistics for the change from baseline in pulse oximetry, measured as peripheral arterial oxygen saturation (SpO2), at fixed timepoints are reported.
| percent hemoglobin oxygen saturation | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| To day 3 | 3.86 ± 5.90 | 2.79 ± 6.48 |
| To day 7 | 4.37 ± 6.53 | 2.45 ± 7.79 |
| To day 14 | 5.41 ± 5.87 | 4.09 ± 7.05 |
| To day 21 | 4.32 ± 6.62 | 3.12 ± 4.55 |
| To day 28 | 5.95 ± 5.42 | 5.46 ± 7.19 |
| Hospital discharge (Up to Day 41) | 4.53 ± 2.20 | 9.25 ± 0.35 |
FiO2 is a parameter of lung function representing the fraction of oxygen in the inspired air, ranging from 0.21 (room air) to 1.00 (100% oxygen). The endpoint assesses the change from baseline in FiO2 levels at predefined timepoints during the study.
| fraction (0.21-1.00) | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 3 | -0.010 ± 0.144 | -0.038 ± 0.140 |
| Day 7 | -0.061 ± 0.151 | -0.072 ± 0.169 |
| Day 14 | -0.071 ± 0.135 | -0.071 ± 0.180 |
| Day 21 | -0.061 ± 0.131 | -0.082 ± 0.111 |
| Day 28 | -0.078 ± 0.119 | -0.086 ± 0.097 |
| Hospital discharge (Up to Day 41) | -0.055 ± 0.078 | 0.000 |
The PaO2/FiO2 ratio is a parameter of lung function that reflects the efficiency of oxygen transfer from the lungs to the blood. It is calculated as the ratio between the arterial partial pressure of oxygen (PaO2, measured in mmHg) and the fraction of inspired oxygen (FiO2, expressed as a fraction ranging from 0.21 to 1.00). This endpoint assesses the change from baseline in the PaO2/FiO2 ratio at predefined timepoints during the study.
| ratio | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 3 | 66.51 ± 115.49 | 54.52 ± 97.65 |
| Day 7 | 105.38 ± 122.94 | 109.57 ± 138.44 |
| Day 14 | 148.84 ± 128.09 | 146.72 ± 129.19 |
| Day 21 | 101.87 ± 134.94 | 180.14 ± 164.18 |
| Day 28 | 177.58 ± 133.95 | 192.55 ± 116.18 |
| Hospital discharge (Up to Day 41) | 172.34 ± 196.54 | 137.62 |
The SpO2/FiO2 ratio is a noninvasive indicator of lung function and oxygenation efficiency, calculated as the ratio between peripheral oxygen saturation (SpO2, expressed as a percentage) and the fraction of inspired oxygen (FiO2, expressed as a fraction ranging from 0.21 to 1.00). This endpoint assesses the change from baseline in the SpO2/FiO2 ratio at predefined timepoints during the study.
| ratio (SpO2 [%] / FiO2 [fraction]) | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 3 | 19.63 ± 103.39 | 38.01 ± 104.26 |
| Day 7 | 67.42 ± 108.71 | 81.50 ± 131.69 |
| Day14 | 98.30 ± 97.90 | 96.20 ± 122.21 |
| Day 21 | 74.69 ± 107.88 | 101.45 ± 94.49 |
| Day 28 | 109.34 ± 93.37 | 118.75 ± 82.93 |
Results for all-cause mortality rates in the FAS are reported, at day 28, day 60, and day 90. Analysis was based on logistic regression model with Multiple Imputation using retrieve dropouts with proportion of patients died up to Day 28 as dependent variable, treatment, disease severity at baseline (NIAID-OS \<=5 vs. NIAID-OS 6), age class (\<65, \>= 65 years), sex and presence of concomitant disease at baseline as qualitative independent variables.
| % participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 28 | 2.608 (NA to 5.219) | 5.701 (1.612 to 9.790) |
| Day 60 | 6.990 (2.326 to 11.653) | 11.310 (4.956 to 17.664) |
| Day 90 | 7.898 (2.890 to 12.906) | 11.910 (5.448 to 18.371) |
Hospital Re-admission by Day 90 and 180 in the FAS is presented. The number of participants is expressed as unadjusted proportion.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 90 | 30 | 29 |
| Day 180 | 34 | 37 |
The median time to discharge or to a NEWS (National Early Warning Score) of ≤ 2 (for 24 hours), whichever occurs first, was expressed using a "time to event" approach, and measured in days. NIAID-OS, National Early Warning Score (NEWS) was evaluated daily until day 28 (or hospital discharge). In a scored system standardizing the assessment of acute-illness severity in the NHS, NEWS includes Blood Pressure (BP), Heart Rate (HR), Respiratory Rate (RR), body temperature, level of consciousness (A, V, P, U), peripheral arterial oxygen saturation (SpO2) and supplemental oxygen. Time to discharge or to a NEWS of \<= 2 (for 24 hours) = Min(Date of discharge, Date of NEWS of \<= 2 (for 24 hours)) - Day 1 date + 1. Date of NEWS of \<= 2 (for 24 hours): Given two consecutive days with NEWS of \<= 2, the date of the first assessment has been considered.
| days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Time to Discharge or to a NEWS (National Early Warning Score) of ≤ 2 (for 24 Hours), Whichever Occurs First | 5 (4.0 to 6.0) | 5 (5.0 to 6.0) |
The EQ-5D-5L asks patients to indicate whether they have no, slight, moderate, severe, extreme problems on each of 5 dimensions of health: mobility; self-care; usual activities; pain/discomfort; anxiety/depression.The count of patients of each level (1 - no problems, 2 - slight problems, 3 - moderate problems, 4 - severe problems, 5 - extreme problems) for each of the 5 dimensions were reported. The higher the score for each dimension (range 1-5), the worse the outcome.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Mobility - Day 90 — 1 - no problem | 61 | 54 |
| Mobility - Day 90 — 2 - slight problems | 41 | 29 |
| Mobility - Day 90 — 3 - moderate problems | 10 | 16 |
| Mobility - Day 90 — 4 - severe problems | 5 | 5 |
| Mobility - Day 90 — 5 - extreme problems | 3 | 4 |
| Mobility - Day 180 — 1 - no problem | 31 | 45 |
| Mobility - Day 180 — 2 - slight problems | 26 | 20 |
| Mobility - Day 180 — 3 - moderate problems | 9 | 10 |
| Mobility - Day 180 — 4 - severe problems | 2 | 3 |
| Mobility - Day 180 — 5 - extreme problems | 3 | 3 |
| Self-care - Day 90 — 1 - no problem | 83 | 73 |
| Self-care - Day 90 — 2 - slight problems | 21 | 20 |
| Self-care - Day 90 — 3 - moderate problems | 9 | 6 |
| Self-care - Day 90 — 4 - severe problems | 4 | 5 |
| Self-care - Day 90 — 5 - extreme problems | 3 | 4 |
| Self-care - Day 180 — 1 - no problem | 46 | 57 |
| Self-care - Day 180 — 2 - slight problems | 15 | 14 |
| Self-care - Day 180 — 3 - moderate problems | 7 | 4 |
| Self-care - Day 180 — 4 - severe problems | 2 | 4 |
| Self-care - Day 180 — 5 - extreme problems | 1 | 2 |
| Usual activities - Day 90 — 1 - no problem | 52 | 50 |
| Usual activities - Day 90 — 2 - slight problems | 36 | 33 |
| Usual activities - Day 90 — 3 - moderate problems | 20 | 14 |
| Usual activities - Day 90 — 4 - severe problems | 7 | 5 |
| Usual activities - Day 90 — 5 - extreme problems | 5 | 5 |
| Usual activities - Day 180 — 1 - no problem | 31 | 38 |
| Usual activities - Day 180 — 2 - slight problems | 17 | 24 |
| Usual activities - Day 180 — 3 - moderate problems | 15 | 11 |
| Usual activities - Day 180 — 4 - severe problems | 5 | 4 |
| Usual activities - Day 180 — 5 - extreme problems | 3 | 3 |
| Pain/discomfort - Day 90 — 1 - no problem | 66 | 58 |
| Pain/discomfort - Day 90 — 2 - slight problems | 33 | 38 |
| Pain/discomfort - Day 90 — 3 - moderate problems | 16 | 11 |
| Pain/discomfort - Day 90 — 4 - severe problems | 3 | 1 |
| Pain/discomfort - Day 90 — 5 - extreme problems | 1 | 0 |
| Pain/discomfort - Day 180 — 1 - no problem | 36 | 45 |
| Pain/discomfort - Day 180 — 2 - slight problems | 21 | 25 |
| Pain/discomfort - Day 180 — 3 - moderate problems | 9 | 11 |
| Pain/discomfort - Day 180 — 4 - severe problems | 4 | 0 |
| Pain/discomfort - Day 180 — 5 - extreme problems | 0 | 0 |
| Anxiety/Depression - Day 90 — 1 - no problem | 62 | 69 |
| Anxiety/Depression - Day 90 — 2 - slight problems | 33 | 32 |
| Anxiety/Depression - Day 90 — 3 - moderate problems | 21 | 6 |
| Anxiety/Depression - Day 90 — 4 - severe problems | 2 | 1 |
| Anxiety/Depression - Day 90 — 5 - extreme problems | 2 | 0 |
| Anxiety/Depression - Day 180 — 1 - no problem | 38 | 51 |
| Anxiety/Depression - Day 180 — 2 - slight problems | 20 | 24 |
| Anxiety/Depression - Day 180 — 3 - moderate problems | 11 | 4 |
| Anxiety/Depression - Day 180 — 4 - severe problems | 1 | 1 |
| Anxiety/Depression - Day 180 — 5 - extreme problems | 1 | 1 |
The summary of IMV/ECMO duration by day 90 and day 180 for the FAS is presented. The duration of IMV/ECMO use by day 90 was calculated as the total number of days between day 1 and the last available assessment day (≥ day 83) during which the participant was either receiving IMV/ECMO or had a NIAID-OS score of 7. Participants with less than 83 days of follow-up were considered non-evaluable for this endpoint. Similarly, the duration of IMV/ECMO by day 180 was calculated using the same methodology.
| Days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 90 | 0.0 ± 0.0 | 0.3 ± 2.6 |
| Day 180 | 0.0 ± 0.0 | 0.1 ± 0.7 |
Unadjusted proportion of ICU admission is reported as number and percentage of participants requiring ICU admission by day 90 and day 180.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 90 | 25 | 20 |
| Day 180 | 26 | 20 |
Results for the Intensive Care Unit length of stay (days) by day 90 and day 180 in the FAS are reported.
| Days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 90 | 0.9 ± 2.5 | 1.0 ± 3.9 |
| Day 180 | 0.7 ± 2.4 | 0.8 ± 2.2 |
Results for hospital length of stay (days) by day 90 and 180 in the FAS are reported.
| Days | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 90 | 9.8 ± 8.4 | 9.9 ± 10 |
| Day 180 | 12.0 ± 12.7 | 10.5 ± 8.5 |
Occurrence of infections was expressed as the unadjusted proportion of participants with at least one infection by days 90 and 180 in the FAS.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Day 90 | 21 | 19 |
| Day 180 | 23 | 19 |
A TEAE is defined as any adverse event reported in the study having a possible, probable, or highly probable relationship to investigational product. A serious AE is defined as any untoward medical occurrence that at any dose: * results in death. * is life-threatening (i.e. the patient was at risk of death at the time of the event. It does not refer to an event which hypothetically might have caused death if it were more severe), * requires inpatient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect * is a medically significant or important medical condition, i.e. an important medical event that based upon appropriate medical judgment, may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed above.
| Participants | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| Number of Subjects with at least one TEAE (n (%)) | 129 | 127 |
| Number of Subjects with at least one serious TEAE (n (%)) | 46 | 56 |
| Number of Subjects with at least one non-Serious TEAE (n (%)) | 115 | 106 |
| Number of Subjects with at least one severe TEAE (n (%)) | 32 | 33 |
| Number of Subjects with at least one TEAE Leading to Discontinuation of IMP (n (%)) | 23 | 24 |
| Number of Subjects with at least one TEAE Leading to Discontinuation of study (n (%)) | 1 | 1 |
| Number of Subjects with at least one TEAE Leading to Death (n (%)) | 16 | 18 |
Collected over Throughout the study, during the treatment period (up to 21 days) and during the follow-up period (till day 180 or EoT) considered together as an "overall period", up to 7 months. Please note: SAF set participants were summarized according to the actual treatment received. Hence n=200 for REP and n=194 for placebo, in serious AE and non-serious AE.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Reparixin + Standard of Care | 16/205 (7.8%) | 46/200 (23%) | 129/200 (64.5%) |
| Placebo + Standard of Care | 19/204 (9.3%) | 56/194 (28.9%) | 127/194 (65.5%) |
| Event | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| PneumoniaRespiratory, thoracic and mediastinal disorders | 10/200 | 11/194 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 6/200 | 9/194 |
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 8/200 | 5/194 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 6/200 | 4/194 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/200 | 4/194 |
| DiarrhoeaGastrointestinal disorders | 0/200 | 3/194 |
| DeathGeneral disorders | 3/200 | 0/194 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/200 | 2/194 |
| Atrial fibrillationCardiac disorders | 1/200 | 2/194 |
| MyocarditisCardiac disorders | 0/200 | 2/194 |
| Event | Reparixin + Standard of Care | Placebo + Standard of Care |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 15/200 | 11/194 |
| HypokalaemiaMetabolism and nutrition disorders | 15/200 | 14/194 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 11/200 | 14/194 |
| NauseaGastrointestinal disorders | 11/200 | 8/194 |
| HypotensionVascular disorders | 11/200 | 4/194 |
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 10/200 | 6/194 |
| HypertensionVascular disorders | 10/200 | 7/194 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 6/200 | 9/194 |
| Acute kidney injuryRenal and urinary disorders | 9/200 | 1/194 |
| ConstipationGastrointestinal disorders | 2/200 | 8/194 |
FAS: All randomized patients who received at least one dose of the investigational product. FAS population was analyzed according to intention-to-treat principle, ie, by treatment allocation regardless of happening of intercurrent events. The FAS population was used to analyze results on efficacy data and demographics.
| Age, Categorical(Participants) | Reparixin + Standard of Care | Placebo + Standard of Care | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 84 | 79 | 163 |
| >=65 years | 117 | 114 | 231 |
| Age, Continuous(years) | Reparixin + Standard of Care | Placebo + Standard of Care | Total |
|---|---|---|---|
| Mean | 64.3 ± 15.7 | 65.9 ± 14.9 | 65.1 ± 15.3 |
| Sex: Female, Male(Participants) | Reparixin + Standard of Care | Placebo + Standard of Care | Total |
|---|---|---|---|
| Female | 97 | 76 | 173 |
| Male | 104 | 117 | 221 |
| Ethnicity (NIH/OMB)(Participants) | Reparixin + Standard of Care | Placebo + Standard of Care | Total |
|---|---|---|---|
| Hispanic or Latino | 33 | 39 | 72 |
| Not Hispanic or Latino | 168 | 154 | 322 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Reparixin + Standard of Care | Placebo + Standard of Care | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 1 | 2 |
| Asian | 2 | 4 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 18 | 14 | 32 |
| White | 176 | 168 | 344 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 6 | 10 |
| Region of Enrollment(participants) | Reparixin + Standard of Care | Placebo + Standard of Care | Total |
|---|---|---|---|
| Austria | 19 | 16 | 35 |
| Argentina | 28 | 29 | 57 |
| Turkey | 21 | 19 | 40 |
| United States | 79 | 80 | 159 |
| Italy | 47 | 43 | 90 |
| Australia | 2 | 3 | 5 |
| Germany | 5 | 3 | 8 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Apr 2022 to primary completion in Jul 2024, 27 months.
Results were first posted in Feb 2026, 1 year 6 months after primary completion.
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Studies of the drug tested here: Reparixin