Clinical trial NCT04878055: Study on Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With Severe COVID-19 Pneumonia.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Viral
Keywords: Covid-19
SARS-CoV-2
Pneumonia
Severe pneumonia
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2021-05-07
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: subjects will be randomized with a 2:1 randomization ratio
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 90, male and female subject of any race
2. Reverse transcriptase Polymerase Chain Reaction (rt-PCR)-confirmed COVID-19 infection based on a nasal / oropharyngeal swab within 10 days before randomization
3. 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.
4. 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).
5. Radiological chest imaging (X-rays, CT scan) confirms lung involvement and inflammation.

Exclusion Criteria:

1. Cannot obtain informed consent.
2. Hepatic dysfunction with Child Pugh score B or C, or ALT or AST\> 5 times the upper limit.
3. 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.
4. Bacterial sepsis (besides COVID-19 sepsis).
5. Known congenital or acquired immune deficiency.
6. 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.

Primary outcomes:
measure: Proportion of Patients Alive and Free of Respiratory Failure at Day 28
timeFrame: At day 28
Secondary outcomes:
measure: Proportion of Patients Alive and Free of Respiratory Failure at Day 60
timeFrame: At day 60
measure: Mortality Rates up to Day 28
timeFrame: Up to Day 28
measure: Incidence of ICU Admission Until Day 28
timeFrame: Until day 28
measure: Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28
timeFrame: Until Day 28
measure: Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints
timeFrame: At Days 3, 7(±1),14(±2), 21(±2) and 90(±2) after randomization (randomization = day 1)
measure: Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS)
timeFrame: Day 1 (baseline), Days 3, 7, 14, 21, 28.
measure: Percentage of Participants With Clinical Improvement 1 up to Day 28
timeFrame: At day 28
measure: Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS)
timeFrame: Day 1 (baseline), Days 3, 7, 14, 21, 28
measure: Percentage of Participants With Clinical Improvement 2 up to Day 28
timeFrame: At Day 28
measure: Time to Discharge From Hospital up to Day 28
timeFrame: Day 1 (baseline), Days 3, 7, 14, 21, 28
measure: Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2).
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Duration of Supplemental Oxygen Treatment up to Day 28
timeFrame: From baseline up to day 28
measure: Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60
timeFrame: day 28 and Day 60
measure: Duration of Non-invasive Mechanical Ventilation up to Day 60
timeFrame: From baseline up to day 60
measure: Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60
timeFrame: Up to day 60
measure: Duration of ICU Admission up to Day 60
timeFrame: Up to day 60
measure: Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2)
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio.
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP)
timeFrame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
measure: Mortality Rates up to Days 60 and 90
timeFrame: up to Days 60 and 90
measure: Freedom From (Time to) Death or Respiratory Failure up to Day 90
timeFrame: at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90
measure: Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc.
timeFrame: Throughout the study, till Day 90 (= end of the follow-up period).
Other outcomes:
Locations:
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates, 2150 Pennsylvania Avenue NW
state: District of Columbia
city: Greenwood
country: United States
facility: Franciscan Alliance, 421 N Emerson Ave,
state: Indiana
city: Bologna
country: Italy
facility: Policlinico S. Orsola Malpighi UO di Pneumologia e Terapia Int. Respiratoria
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino Malattie infettive e tropicali
city: L'Aquila
country: Italy
facility: Ospedale regionale San Salvatore U.O.C. Anestesia e Rianimazione
city: Milano
country: Italy
facility: IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive
city: MIlan
country: Italy
facility: IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione
city: Milan
country: Italy
facility: ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive
city: Monza
country: Italy
facility: ASST-Monza Ospedale San Gerardo Malattie Infettive
city: Napoli
country: Italy
facility: A.O.U. Federico II Malattie Infettive del Policlinico Federico II
city: Napoli
country: Italy
facility: Università della Campania "Luigi Vanvitelli" Dipartimento di Malattie Infettive
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico UOC Anestesia e Rianimazione
city: Roma
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I, UOC Malattie Infettive
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli" - Istituto di Clinica delle Malattie Infettive
city: Varese
country: Italy
facility: ASST dei Sette Laghi Ospedale di Circolo e Fondazione Macchi Struttura Complessa Malattie infettive e tropicali
city: Verona
country: Italy
facility: A.O.U. Integrata di Verona U.O. Medicina Respiratoria, sezione di Medicina Interna
Study officials:
affiliation: Ospedale San Raffaele
name: Giovanni Landoni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: