Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With COVID-19 Pneumonia

Dompé Farmaceutici S.p.A4 sites in 2 countries56 target enrollmentMay 5, 2020

ConditionsSevere Pneumonia

InterventionsReparixin Standard of care

DrugsReparixin Standard of care

Overview

Phase: Phase 2
Intervention: Reparixin
Conditions: Severe Pneumonia
Sponsor: Dompé Farmaceutici S.p.A
Enrollment: 56
Locations: 4
Primary Endpoint: Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Detailed Description

This clinical trial is an adaptive phase 2/3, randomized, controlled multicenter study on the efficacy and safety of Reparixin in the treatment of hospitalized patients with COVID-19 pneumonia. 48 patients are planned to be enrolled in Phase 2 and an estimated total of 111 patients are planned to be enrolled up to the end of Phase 3, with a randomization 2:1 Reparixin vs Control (Standard of care). In the phase 2 segment of this study, patients are randomized 2:1 to Reparixin oral tablets 1200 mg (Group 1, active treatment) or standard of care (Group 2, control arm). In case of worsening (e.g. need of ICU and/or mechanical ventilation) after the first 24hrs, patients are offered a rescue medication with no restriction from the sponsor and fully based on their physicians' judgement. In the phase 3 segment of this study, it is planned that patients are randomized 2:1 to Reparixin or standard of care. The Phase 3 design will be reassessed and decided based on the results of the Phase 2.

Registry

clinicaltrials.gov

Start Date

May 5, 2020

End Date

February 2, 2021

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Dompé Farmaceutici S.p.A

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Phase 2 Inclusion Criteria:
•Confirmed COVID-19 diagnosis
•At least one of the following: # Respiratory distress, RR ≥ 30 breaths/min without oxygen; # Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2) \>100 \<300mmHg
•(1mmHg = 0.133kPa).
•Chest imaging confirms lung involvement and inflammation.
•Inflammatory status as documented by at least one of the following: Lactate dehydrogenase (LDH) \> normal range, C-reactive protein (CRP) ≥ 100mg/L or IL-6 ≥ 40pg/mL, serum ferritin ≥ 900ng/mL, XDP \>20mcg/mL.
•Phase 3 Inclusion Criteria: Same as above; other criteria TBD based on Phase 2 outcomes.

Exclusion Criteria

•Phase 2/3 Exclusion Criteria:
•Cannot obtain informed consent.
•Severe hepatic dysfunction (Child Pugh score ≥ C, or AST\> 5 times the upper limit); Severe renal dysfunction (estimated glomerular filtration rate ≤ 30mL / min / 1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
•Patients with hypersensitivity to ibuprofen or to more than one non steroidal anti-inflammatory drug or to more than one medication belonging to the class of sulfonamides (e.g. sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib; hypersensitivity to sulphanilamide antibiotics alone, e.g. sulfamethoxazole, does not qualify for exclusion)
•Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
•Pregnant and lactating women and those planning to get pregnant.
•Participated in other interventional clinical trials with investigational medicinal products, not considered suitable for this study by the researchers.
•At the time of enrollment, patients not in a clinical condition compatible with the oral administration of the study drug.

Arms & Interventions

Reparixin

Reparixin oral tablets 1200 mg TID for 7 days

Intervention: Reparixin

Standard of care

Intervention: Standard of care

Outcomes

Primary Outcomes

Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events

Time Frame: 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

Secondary Outcomes

Phase 2 - Oxygen Cumulative Duration During the Study(Week 1, EOT, EOS)
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Cumulative ICU Stay(Day 1, Day 2, Week 1, EOT, EOS)
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale(Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS))
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints(Baseline, Day 1, Day 2, Week 1, EOT and EOS)
Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Lung Exudation by Severity and by Timepoint(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Change From Baseline in Reactive Protein (CRP)(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points(At day 1, day 2, week 1, day 21(end of treatment, EOT), EOS (end of study, i.e. 7±3 days after EOT))
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale(Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS))
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2(At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Oxygen Cumulative Quantity During the Study(Week 1, EOT and EOS)
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio](Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification(day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Lung Damage Extension by Severity and by Timepoint(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)(Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period))