Last reviewed · How we verify

NCT04794803

Reparixin in COVID-19 Pneumonia - Efficacy and Safety

Terminated Phase 2, PHASE3 Results posted Last updated 8 January 2024
What this trial tests

Phase 2, PHASE3 trial testing Reparixin in Severe Pneumonia in 56 participants. Terminated before completion.

Timeline
5 May 2020
Primary endpoint
27 November 2020
2 February 2021

Quick facts

Lead sponsorDompé Farmaceutici S.p.A
PhasePhase 2, PHASE3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment56
Start date5 May 2020
Primary completion27 November 2020
Estimated completion2 February 2021
Sites4 locations across Italy, Brazil

Drugs / interventions tested

Conditions studied

Sponsor

Dompé Farmaceutici S.p.A — full company profile →

Who can join

Adults 18 to 90, any sex, with Severe Pneumonia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events Primary · Up to Day 1

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

Composite event
GroupValue95% CI
Reparixin (FAS)16.76.4 – 32.8
Standard of Care (FAS)42.120.3 – 66.5
Supplemental oxygen requirement based on PaO2/FiO2
GroupValue95% CI
Reparixin (FAS)13.94.7 – 29.5
Standard of Care (FAS)26.39.1 – 51.2
Invasive Mechanical ventilation
GroupValue95% CI
Reparixin (FAS)2.80.1 – 14.5
Standard of Care (FAS)5.30.1 – 26.0
Admission to ICU
GroupValue95% CI
Reparixin (FAS)2.80.1 – 14.5
Standard of Care (FAS)0.00.0 – 17.6
Use of a rescue medication for any reason
GroupValue95% CI
Reparixin (FAS)0.00.0 – 9.7
Standard of Care (FAS)26.39.1 – 51.2
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points Secondary · At day 1, day 2, week 1, day 21(end of treatment, EOT), EOS (end of study, i.e. 7±3 days after EOT)

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;

Day 1
GroupValue95% CI
Reparixin (FAS)0.00.0 – 10.0
Standard of Care (FAS)0.00.0 – 17.6
Day 2
GroupValue95% CI
Reparixin (FAS)0.00.0 – 10.0
Standard of Care (FAS)0.00.0 – 18.5
Week 1
GroupValue95% CI
Reparixin (FAS)23.510.7 – 41.2
Standard of Care (FAS)17.63.8 – 43.4
EOT
GroupValue95% CI
Reparixin (FAS)26.512.9 – 44.4
Standard of Care (FAS)26.39.1 – 51.2
EOS
GroupValue95% CI
Reparixin (FAS)61.540.6 – 79.8
Standard of Care (FAS)55.621.2 – 86.3
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale Secondary · Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)

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 ran

Baseline
GroupValue95% CI
Reparixin (FAS)0
Standard of Care (FAS)1
Day 1
GroupValue95% CI
Reparixin (FAS)7
Standard of Care (FAS)2
Day 2
GroupValue95% CI
Reparixin (FAS)12
Standard of Care (FAS)2
Week 1
GroupValue95% CI
Reparixin (FAS)23
Standard of Care (FAS)6
EOT
GroupValue95% CI
Reparixin (FAS)20
Standard of Care (FAS)6
EOS
GroupValue95% CI
Reparixin (FAS)16
Standard of Care (FAS)3
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale Secondary · Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)

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.

Baseline
GroupValue95% CI
Reparixin (FAS)56.9± 37.3
Standard of Care (FAS)4.0± 5.5
to Day 1
GroupValue95% CI
Reparixin (FAS)4.3± 8.5
Standard of Care (FAS)20.0± 40.0
to Day 2
GroupValue95% CI
Reparixin (FAS)32.3± 40.3
Standard of Care (FAS)44.8± 51.7
Week 1
GroupValue95% CI
Reparixin (FAS)29.0± 34.0
Standard of Care (FAS)86.0± 5.3
EOT
GroupValue95% CI
Reparixin (FAS)33.0± 41.8
Standard of Care (FAS)89.7± 0.6
EOS
GroupValue95% CI
Reparixin (FAS)22.5± 31.8
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints Secondary · Baseline, Day 1, Day 2, Week 1, EOT and EOS

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.

Baseline
GroupValue95% CI
Reparixin (FAS)36.4± 0.5
Standard of Care (FAS)36.5± 0.5
to Day 1
GroupValue95% CI
Reparixin (FAS)-0.2± 0.5
Standard of Care (FAS)0.2± 0.9
to Day 2
GroupValue95% CI
Reparixin (FAS)-0.1± 0.7
Standard of Care (FAS)-0.1± 0.6
to Week 1
GroupValue95% CI
Reparixin (FAS)-0.1± 0.6
Standard of Care (FAS)-0.2± 0.6
to EOT
GroupValue95% CI
Reparixin (FAS)-0.2± 0.6
Standard of Care (FAS)-0.4± 0.6
to EOS
GroupValue95% CI
Reparixin (FAS)-0.1± 0.5
Standard of Care (FAS)-0.5± 0.6
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2 Secondary · At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

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

Day 1 - subjects worsened (%)
GroupValue95% CI
Reparixin (FAS)7.40.9 – 24.3
Standard of Care (FAS)14.31.8 – 42.8
Day 2 - subjects worsened (%)
GroupValue95% CI
Reparixin (FAS)12.93.6 – 29.8
Standard of Care (FAS)20.04.3 – 48.1
Week 1 - subjects worsened (%)
GroupValue95% CI
Reparixin (FAS)0.00.0 – 13.2
Standard of Care (FAS)21.44.7 – 50.8
EOT - subjects worsened (%)
GroupValue95% CI
Reparixin (FAS)0.00.0 – 11.9
Standard of Care (FAS)8.30.2 – 38.5
EOS - subjects worsened (%)
GroupValue95% CI
Reparixin (FAS)0.00.0 – 30.8
Standard of Care (FAS)0.00.0 – 70.8
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification Secondary · day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

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

Day 1 - subjects worsened
GroupValue95% CI
Reparixin (FAS)5.60.7 – 18.7
Standard of Care (FAS)0.00.0 – 17.6
Day 2 - subjects worsened
GroupValue95% CI
Reparixin (FAS)5.60.7 – 18.7
Standard of Care (FAS)5.30.1 – 26.0
Week 1 - subjects worsened
GroupValue95% CI
Reparixin (FAS)2.90.1 – 15.3
Standard of Care (FAS)17.63.8 – 43.4
EOT - subjects worsened
GroupValue95% CI
Reparixin (FAS)2.90.1 – 14.9
Standard of Care (FAS)15.83.4 – 39.6
EOS - subjects worsened
GroupValue95% CI
Reparixin (FAS)3.60.1 – 18.3
Standard of Care (FAS)8.30.2 – 38.5
Phase 2 - Oxygen Cumulative Duration During the Study Secondary · Week 1, EOT, EOS

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.

week 1
GroupValue95% CI
Reparixin (FAS)141.93± 55.68
Standard of Care (FAS)130.22± 80.89
EOT
GroupValue95% CI
Reparixin (FAS)151.55± 75.53
Standard of Care (FAS)134.00± 86.21
EOS
GroupValue95% CI
Reparixin (FAS)195.26± 198.62
Standard of Care (FAS)155.71± 135.93
Phase 2 - Oxygen Cumulative Quantity During the Study Secondary · Week 1, EOT and EOS

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.

Week 1
GroupValue95% CI
Reparixin (FAS)24.99± 22.22
Standard of Care (FAS)29.20± 29.51
EOT
GroupValue95% CI
Reparixin (FAS)25.64± 22.16
Standard of Care (FAS)29.73± 31.53
EOS
GroupValue95% CI
Reparixin (FAS)26.54± 22.31
Standard of Care (FAS)33.38± 31.64
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall Secondary · Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

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.

Baseline - subjects requiring
GroupValue95% CI
Reparixin (FAS)11.13.1 – 26.1
Standard of Care (FAS)10.51.3 – 33.1
Day1 - subjects requiring
GroupValue95% CI
Reparixin (FAS)11.13.1 – 26.1
Standard of Care (FAS)10.51.3 – 33.1
Day 2 - subjects requiring
GroupValue95% CI
Reparixin (FAS)11.43.2 – 26.7
Standard of Care (FAS)16.73.6 – 41.4
Week 1- subjects requiring
GroupValue95% CI
Reparixin (FAS)8.81.9 – 23.7
Standard of Care (FAS)11.81.5 – 36.4
EOT - subjects requiring
GroupValue95% CI
Reparixin (FAS)8.61.8 – 23.1
Standard of Care (FAS)5.30.1 – 26.0
EOS -subjects requiring
GroupValue95% CI
Reparixin (FAS)0.00.0 – 12.8
Standard of Care (FAS)0.00.0 – 30.8
Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall Secondary · Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

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

Week 1
GroupValue95% CI
Reparixin (FAS)162.54± 58.92
Standard of Care (FAS)142.42± 44.89
EOT
GroupValue95% CI
Reparixin (FAS)149.99± 53.23
Standard of Care (FAS)146.86± 43.80
EOS
GroupValue95% CI
Reparixin (FAS)179.51± 78.30
Standard of Care (FAS)154.86± 56.52
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need Secondary · Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)

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.

Baseline - subjects admitted to ICU
GroupValue95% CI
Reparixin (FAS)2.80.1 – 14.5
Standard of Care (FAS)5.30.1 – 26.0
Day 1 - subjects admitted to ICU
GroupValue95% CI
Reparixin (FAS)2.80.1 – 14.5
Standard of Care (FAS)5.30.1 – 26.0
Day 2 - subjects admitted to ICU
GroupValue95% CI
Reparixin (FAS)5.70.7 – 19.2
Standard of Care (FAS)5.60.1 – 27.3
Week 1 - subjects admitted to ICU
GroupValue95% CI
Reparixin (FAS)2.90.1 – 15.3
Standard of Care (FAS)0.00.0 – 19.5
EOT - subjects admitted to ICU
GroupValue95% CI
Reparixin (FAS)2.90.1 – 14.9
Standard of Care (FAS)0.00.0 – 17.6
EOS - subjects admitted to ICU
GroupValue95% CI
Reparixin (FAS)0.00.0 – 30.8
Standard of Care (FAS)0.00.0 – 12.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Throughout the study, till day 21. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Reparixin (SAF)
Serious: 1/36 (3%)
Deaths: 1/36
Standard of Care (SAF)
Serious: 1/19 (5%)
Deaths: 3/19

Serious adverse events (1 terms)

ReactionSystemReparixin (SAF)Standard of Care (SAF)
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (3 terms — click to expand)

ReactionSystemReparixin (SAF)Standard of Care (SAF)
DiarrhoeaGastrointestinal disorders
Post procedural discomfortInjury, poisoning and procedural complications
Respiratory failureRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Respiratory failure.

Data from ClinicalTrials.gov NCT04794803 adverse events section.

Sponsor's own description

* Phase 2 Study Objectives: efficacy and safety of of Reparixin treatment as compared to the control arm in adult patients with severe COVID-19 pneumonia * Phase 3 Study Objectives: efficacy and safety of Reparixin treatment as compared to the control arm in adult patients with moderate or severe COVID-19 pneumonia

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
    Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
  2. The Role of Interleukin-8 in Lung Inflammation and Injury: Implications for the Management of COVID-19 and Hyperinflammatory Acute Respiratory Distress Syndrome.
    Cesta MC, Zippoli M, Marsiglia C, Gavioli EM, et al · · 2021 · cited 108× · PMID 35095519 · DOI 10.3389/fphar.2021.808797
  3. Self-sustaining IL-8 loops drive a prothrombotic neutrophil phenotype in severe COVID-19.
    Kaiser R, Leunig A, Pekayvaz K, Popp O, et al · · 2021 · cited 89× · PMID 34403366 · DOI 10.1172/jci.insight.150862
  4. Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis.
    Cesta MC, Zippoli M, Marsiglia C, Gavioli EM, et al · · 2023 · cited 74× · PMID 36239164 · DOI 10.1002/eji.202250010
  5. Multifaceted Roles of Chemokine C-X-C Motif Ligand 7 in Inflammatory Diseases and Cancer.
    Wu Q, Tu H, Li J. · · 2022 · cited 25× · PMID 35837284 · DOI 10.3389/fphar.2022.914730
  6. A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia.
    Landoni G, Piemonti L, Monforte AD, Grossi P, et al · · 2022 · cited 25× · PMID 35618953 · DOI 10.1007/s40121-022-00644-6
  7. Myeloid cells in COVID-19 microenvironment.
    Qin G, Liu S, Yang L, Yu W, et al · · 2021 · cited 21× · PMID 34707085 · DOI 10.1038/s41392-021-00792-0
  8. Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity.
    Delshad M, Safaroghli-Azar A, Pourbagheri-Sigaroodi A, Poopak B, et al · · 2021 · cited 21× · PMID 34304001 · DOI 10.1016/j.intimp.2021.107995

Verify or expand the search:

Other trials of Reparixin

Trials testing the same drug.

Other recruiting trials for Severe Pneumonia

Currently open trials in the same condition.

Other Dompé Farmaceutici S.p.A trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04794803.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing