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

Sponsor

Dompé Farmaceutici S.p.A (Industry)

Overall Status

Completed

CT.gov ID

NCT04878055

Collaborator

(none)

312

Enrollment

Locations

Arms

8.5

Actual Duration (Months)

18.4

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Viral	Drug: Reparixin Other: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

312 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

subjects will be randomized with a 2:1 randomization ratiosubjects will be randomized with a 2:1 randomization ratio

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 14, 2021

Actual Primary Completion Date :

Sep 30, 2021

Actual Study Completion Date :

Oct 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reparixin 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 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily). Other Names: DF 1681Y
Placebo Comparator: Placebo 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 Matched placebo, i.e. 2 tablets for the total of three daily administrations (6 tablets daily).

Arm

Intervention/Treatment

Experimental: Reparixin

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

2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily).

Other Names:

DF 1681Y

Placebo Comparator: Placebo

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

Matched placebo, i.e. 2 tablets for the total of three daily administrations (6 tablets daily).

Outcome Measures

Primary Outcome Measures

Proportion of patients alive and free of respiratory failure at Day 28 [At day 28]

Secondary Outcome Measures

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The George Washington University Medical Faculty Associates, 2150 Pennsylvania Avenue NW	Washington	District of Columbia	United States	20037
2	Franciscan Alliance, 421 N Emerson Ave,	Greenwood	Indiana	United States	46143
3	Policlinico S. Orsola Malpighi UO di Pneumologia e Terapia Int. Respiratoria	Bologna		Italy	40138
4	Ospedale Policlinico San Martino Malattie infettive e tropicali	Genova		Italy	16132
5	Ospedale regionale San Salvatore U.O.C. Anestesia e Rianimazione	L'Aquila		Italy	67100
6	IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza	Milano		Italy	20089
7	ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive	Milano		Italy	20162
8	IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione	MIlan		Italy	20132
9	ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive	Milan		Italy	20142
10	ASST-Monza Ospedale San Gerardo Malattie Infettive	Monza		Italy	20900
11	A.O.U. Federico II Malattie Infettive del Policlinico Federico II	Napoli		Italy	80131
12	Università della Campania "Luigi Vanvitelli" Dipartimento di Malattie Infettive	Napoli		Italy	80133
13	Policlinico Universitario Campus Bio-Medico UOC Anestesia e Rianimazione	Roma		Italy	00128
14	Azienda Ospedaliero-Universitaria Policlinico Umberto I, UOC Malattie Infettive	Roma		Italy	00161
15	Università Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli" - Istituto di Clinica delle Malattie Infettive	Roma		Italy	00168
16	ASST dei Sette Laghi Ospedale di Circolo e Fondazione Macchi Struttura Complessa Malattie infettive e tropicali	Varese		Italy	21100
17	A.O.U. Integrata di Verona U.O. Medicina Respiratoria, sezione di Medicina Interna	Verona		Italy	37124