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

Study Overview
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Brief Summary
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The study objective is to assess Efficacy and safety of Reparixin treatment as compared to placebo (both on top of standard treatment) in adult patients with severe COVID-19 pneumonia.

Detailed Description
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This is a phase 3 clinical trial designed as a randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of Reparixin in hospitalized adult patients with severe COVID-19 pneumonia. Patients will be screened for the participation in the study and eventually randomized based on an unbalanced randomization scheme (2:1) to Reparixin oral tablets (2 x 600 mg TID) for up to 21 days or to placebo. An unequal randomization is justified by the need to gain experience and more safety data with the investigated treatment and by an expected better acceptability of the trial by patients. The placebo control arm is justified by the unavailability of a well-defined standard of care for subjects with COVID-19 pneumonia who are candidates for this study. All patient will receive the standard supportive care based on the patient's clinical need. Follow-up information on the patient's clinical condition will be collected until day 90.

Official Title
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A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With Severe COVID-19 Pneumonia

Conditions
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Pneumonia, Viral

Intervention / Treatment
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* Drug: Reparixin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 90, male and female subject of any race Reverse transcriptase Polymerase Chain Reaction (rt-PCR)-confirmed COVID-19 infection based on a nasal / oropharyngeal swab within 10 days before randomization At least one of the following: 1) Respiratory distress with tachypnea (RR ≥ 24 breaths/min without oxygen); 2) Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2), P/F >100 and <300 mmHg (1mmHg = 0.133kPa), 3) SpO2 ≤ 94% while breathing ambient air. Calculation through validated Sat/FiO2 scales is allowed. P/F value of reference if the last available before the signature of consent. Need of supplemental oxygen (i.e. new use of supplemental oxygen, or increased oxygen requirement if on chronic oxygen) requiring low- or high-flow oxygen or non-invasive mechanical ventilation (7-point WHO-OS category 4 or 5). Radiological chest imaging (X-rays, CT scan) confirms lung involvement and inflammation. Exclusion Criteria: Cannot obtain informed consent. Hepatic dysfunction with Child Pugh score B or C, or ALT or AST> 5 times the upper limit. Renal dysfunction with estimated glomerular filtration rate (MDRD) < 50 mL/min/1.73 m2 or patient receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis. Bacterial sepsis (besides COVID-19 sepsis). Known congenital or acquired immune deficiency. Positive or missing pregnancy test before first drug intake or day 1; pregnant or lactating women; women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception for the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: subjects will be randomized with a 2:1 randomization ratio
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reparixin<br>Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care | Drug: Reparixin<br>* 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily).<br>* Other names: DF 1681Y;|
| Placebo Comparator: Placebo<br>placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care. | Other: Placebo<br>* Matched placebo, i.e. 2 tablets for the total of three daily administrations (6 tablets daily).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients alive and free of respiratory failure at Day 28 |  | At day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients alive and free of respiratory failure at day 60 |  | At day 60 | 
| Mortality rates up to Day 28 |  | Up to Day 28 | 
| Incidence of ICU admission until Day 28 |  | Until day 28 | 
| Time to recovery (category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of clinical improvement (WHO-OS)) until Day 28 |  | Until Day 28 | 
| Proportion of patients alive and free of respiratory failure at fixed time-points |  | At Days 3, 7(±1),14(±2), 21(±2), 28 (±2), 60(±2) after randomization (randomization = day 1) | 
| Incidence of Adverse Events (AEs) |  | From randomization till the last follow-up, up to 90 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, SARS-CoV-2, Pneumonia, Severe pneumonia