Reparixin add-on Therapy to Std Care to Limit Progression in Pts With COVID19 & Other Community Acquired Pneumonia

Severe COVID-19 Clinical Trial

Official title:

Reparixin 1200 mg TID as add-on to SoC to Limit Disease Progression in Hospitalised Patients With COVID-19 and Other Community-Acquired Pneumonia. A Multicentre, Randomised, Double-blinded, Placebo-controlled, Phase III Trial (REPAVID-22)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05254990
• Other study ID #: REP0321
• Secondary ID: 2021-006951-32
• Status: Recruiting
• Phase: Phase 3
• Start date: April 6, 2022
• Est. completion date: October 2024

Study information

• Verified date: June 2024
• Source: Dompé Farmaceutici S.p.A
• Contact: Sophie Toya, MD
• Phone: +1 219 427 2474
• Email: sophie.toya[@]dompe.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective:

• To evaluate the efficacy of oral reparixin versus standard care alone in limiting disease progression in adult patients hospitalised for infectious pneumonia acquired in the community (CAP), including COVID-19.

Secondary objectives:

• To determine the effect of reparixin on several disease severity/progression measures including recovery, ventilatory free days and mortality.

Safety objectives:

• To evaluate the safety of oral reparixin versus placebo in the specific clinical setting.

Description:

Multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase III trial.

It will enrol 526 male and female patients >18 years, hospitalised for CAP (including COVID-19), assigned (1:1) to receive either oral reparixin (treatment group) or matched placebo (control group) three times a day (TID) for up to 21 days. Randomisation will be stratified according to disease severity and site.

All the patients will receive the standard of care based on their clinical need, including COVID-19 and CAP medications, as per local standard therapy at the trial site and in line with international guidelines.

The primary outcome will be evaluated at day 28, secondary will be evaluated from day 3 to day 180.

An independent external data monitoring committee (DMC) will oversee the study and evaluate unblinded interim data for efficacy, futility, and safety.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 526
• Est. completion date: October 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent signed

2. Male and female =18 years old;

3. Patients hospitalized for clinically suspected CAP, defined as the occurrence of (within 48h from hospital admission):

1. at least 1 of the following signs/symptoms: dyspnea, cough, purulent sputum, crackles (rales) and/or rhonchi

2. body temperature > 38°C or <36°C (before or during admission) or leucocytosis (> local ULN)

3. new/increased pulmonary infiltrate(s) by chest imaging

4. Need for non-invasive supplemental oxygen (NIAID-OS 5-6; Appendix 14.4.1);

5. SpO2 <92% at room air, or PaO2/FiO2 (or SpO2/FiO2) <300;

6. Females of child-bearing potential and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception:

1. Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after the last IMP dose

2. A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit until 30 days after the last IMP dose

3. A male sexual partner who agrees to use a male condom with spermicide

4. A sterile sexual partner

Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, with child-bearing potential, pregnancy test result must be negative before first drug intake.

Exclusion Criteria:

1. Treatment with IMV or ECMO (NIAID-OS 7);

2. Hepatic dysfunction: ALT or AST > 5 ULN; history of chronic hepatic disease (defined with Child-Pugh score B or C);

3. Renal dysfunction: estimated glomerular filtration rate (eGFR, MDRD) <50 mL/min/1.73 m2, or need for haemodialysis or hemofiltration;

4. Current use of >2 immunosuppressive medications or immunosuppression status (AIDS, aplastic anaemia, asplenia, systemic chemotherapy within the past 3 months, neutropenia (ANC < local LLN), solid organ or bone marrow transplant recipients)

5. Treatment with prohibited medication within 5 half-lives, and inability to stop during treatment period (see section 5.5.2);

6. Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening

7. History of:

1. intolerance or hypersensitivity to ibuprofen to more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib (hypersensitivity to sulphanilamide antibiotics alone, e.g. sulfamethoxazole does not qualify for exclusion)

2. lactase deficiency, galactosemia or glucose-galactose malabsorption

3. gastrointestinal bleeding or perforation due to previous NSAIDs therapy or recurrent peptic ulcer/haemorrhage

4. allergy to reparixin or any component of the IMP formulation

8. Active bleeding or bleeding diathesis (excluding menses), prior intracranial haemorrhage

9. Participation in other interventional clinical trials

10. Clinical condition not compatible with oral administration of the study drug

11. Pregnancy:

1. positive or missing pregnancy test before first drug intake or day 1;

2. pregnant or lactating women;

3. 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

12. Current hospital stay >72h

13. Complicated CAP-associated conditions, such as fungal pulmonary infection, tuberculosis infection, abscess, empyema, significant bilateral pleural effusion, massive pulmonary embolism

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Infections
• Infectious Pneumonia
• Pneumonia
• Severe COVID-19

Intervention

Drug:
• Reparixin
Reparixin 600 mg tablets, administered orally at the dose of 1200 mg TID (2 tablets TID) as add-on therapy to standard of care up to 21 days. IMP can be taken with a glass of water (about 250 mL) and a light meal or snack, as it is preferable that reparixin is taken with food. However, if the patient is unable to eat, the study drug may still be administered without concomitant food ingestion.

Other:
• Placebo
Administered orally three times a day (TID) as add-on therapy to standard of care up to 21 days. Placebo can be taken with a glass of water (about 250 mL) and a light meal or snack, as it is preferable that placebo is taken with food. However, if the patient is unable to eat, the placebo may still be administered without concomitant food ingestion.

Locations

Country	Name	City	State
Argentina	Hospital Interzonal General de Agudos Dr Jose Penna	Bahia Blanca	Buenos Aires
Argentina	Hospital Aleman	Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Sanatorio Agote	Buenos Aires
Argentina	Hospital Cuenca Alta Nestor Kirchner	Cañuelas	Buenos Aires
Argentina	CEMIC	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Sanatorio Finochietto	Ciudad Autonoma de Buenos Aire	Ciudad Autonoma De Buenos Aires
Argentina	Clinica Adventista Belgrano	Ciudad Autonoma de Buenos Aires
Argentina	Hospital General de Agudos Dr. J. M. Ramos Mejia	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital General de Agudos Dr. Ignacio Pirovano	Ciudad de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Clinica Chutro	Córdoba
Argentina	Nuevo Hospital San Roque	Córdoba
Argentina	Sanatorio Allende	Córdoba
Argentina	Sanatorio Privado de la Cañada - Cordoba	Córdoba
Argentina	Sanatorio Privado Duarte Quiroz De Clinica Colombo SA	Córdoba
Argentina	Hospital Italiano de La Plata	La Plata	Buenos Aires
Argentina	Instituto Medico Platense	La Plata	Buenos Aires
Argentina	Clinica Independencia	Munro	Buenos Aires
Argentina	Sanatorio Britanico S.A.	Rosario	Santa Fe
Argentina	Clinica Mayo de Urgencias Medicas Cruz Blanca SRL	San Miguel de Tucuman	Tucuman
Argentina	Sanatorio Parque S.A. Privado	San Vicente	Cordoba
Argentina	Sanatorio de la Cañada	Villa María	Cordoba
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Mater Hospital Brisbane	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Westmead Hospital	Sydney	New South Wales
Austria	Kepler Universitatsklinikum Med Campus III	Linz
Austria	KH der Barmherzigen Brüder Linz	Linz
Austria	Klinik Favoriten (Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital mit Gottfried von Preyer'schem Kinderspital)	Wien
Austria	Medizinische Universitaet Wien, Medizinische Klinik I, Abteilung für Infektionskrankheiten und Tropenmedizin	Wien
Germany	Albeilung für Kardiologie und Pneumologie	Dachau	Bavaria
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden	Sachsen
Germany	Universitätsmedizin Göttingen	Göttingen	Südniedersachsen
Germany	Medizinische Hochschule	Hannover	Niedersachsen
Germany	Universitaetsklinikum Jena	Jena	Thueringen
Italy	UOC Malattie dell'Apparato Respiratorio, Policlinico di Bari	Bari
Italy	ASST - Ospedale Papa Giovanni XXIII - UOC Pneumologia	Bergamo
Italy	Azienda Ospedaliera Universitaria di Bologna - Ospedale Sant'Orsola	Bologna
Italy	Campus Universitario "Salvatore Venuta", Complesso Clinico, Padiglione B, 8° livello, Pneumologia	Catanzaro
Italy	University Of Genoa - Ospedale Policlinico IRCCS San Martino di Genova	Genova
Italy	ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive	Milan
Italy	ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive	Milan
Italy	IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza	Milan
Italy	IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione	Milan
Italy	Università degli Studi di Milano-Ospedale "L.Sacco" Polo Universitario - ASST Fatebenefratelli Sacco	Milan
Italy	Fondazione Ca' Granda Policlinico Milano	Milano
Italy	ASST-Monza Ospedale San Gerardo Malattie Infettive	Monza
Italy	Clinica Pneumologica "L. Vanvitelli" - Osp Monaldi	Napoli
Italy	Università degli studi di Padova, Unità Malattie Respiratorie	Padova
Italy	AOUP "P.Giaccone" - UOC Pneumologia	Palermo
Italy	Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia, Dipartimento di Scienze Mediche e Malattie Infettive	Pavia
Italy	Struttura semplice di terapia demi-intensiva respiratoria S.C. di pneumologia AO IRCCS Santa Maria Nuova	Reggio Emilia
Turkey	Ankara City Hospital	Ankara
Turkey	Dicle University, Medical Faculty	Diyarbakir
Turkey	Gaziantep Universitesi Sahinbey Arastirma Ve Uygulama Hastanesi	Gaziantep
Turkey	Acibadem Atakent Hospital	Istanbul
Turkey	Dokuz Eylul University Faculty of Medicine	Izmir
Turkey	Kayseri State Hospital	Kayseri
Turkey	Kocaeli Universitesi Tip Fakultesi	Kocaeli
Turkey	Inonu Uni.Med.Faculty	Malatya
Turkey	Karadeniz Tecnical Uni. Med. Fac.	Trabzon
United States	Emory Johns Creek Hospital	Atlanta	Georgia
United States	Augusta University Health - Augusta University Medical Center	Augusta	Georgia
United States	Baptist Hospitals of Southeast Texas	Beaumont	Texas
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	NYU Langone Hospital-Brooklyn	Brooklyn	New York
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Insight Hospital & Medical Center Chicago	Chicago	Illinois
United States	Jesse Brown VA Medical Center	Chicago	Illinois
United States	Northwestern University, Feinberg School of Medicine	Chicago	Illinois
United States	Research Alliance Inc.	Clearwater	Florida
United States	University Hospital - MU Healthcare	Columbia	Missouri
United States	Nuvance Health	Danbury	Connecticut
United States	UC Davis Medical Center - UC Davis Medical Group - Davis	Davis	California
United States	Texoma Medical Center	Denison	Texas
United States	Denver Health	Denver	Colorado
United States	NorthStar Anesthesia / Detroit Medical Center	Detroit	Michigan
United States	Duke University Hospital	Durham	North Carolina
United States	Northshore University HealthSystem	Evanston	Illinois
United States	Methodist Hospital	Gary	Indiana
United States	Hackensack Meridian Health	Hackensack	New Jersey
United States	University of Florida-Jacksonville	Jacksonville	Florida
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University of Southern California	Los Angeles	California
United States	Norton Healthcare	Louisville	Kentucky
United States	MidMichigan Medical Center - Midland	Midland	Michigan
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	New York University Langone Health	New York	New York
United States	Newton-Wellesley Hospital	Newton	Massachusetts
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	UCI Health	Orange	California
United States	Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (OHSU) - Pulmonary Clinic	Portland	Oregon
United States	Virginia Commonwealth University Health	Richmond	Virginia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Mercy Research St Louis	Saint Louis	Missouri
United States	Washington University, School of Medicine	Saint Louis	Missouri
United States	University of Utah Hospitals & Clinics	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida
United States	MD Banner University Medical Center /Arizona University	Tucson	Arizona
United States	MedStar Health Research Institute-Hyatteville, Maryland	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Dompé Farmaceutici S.p.A

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Germany,  Italy,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients dead or requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by day 28 [NIAID-OS 7].	NIAID-OS = National Institute of Allergy and Infectious Disease - Ordinal Scale	Day 28
Secondary	All-cause mortality at day 180		Day 180
Secondary	Proportion of patients alive and discharged at day 28		Day 28
Secondary	Ventilatory-free days (VFD) at day 28	Number of days from Day 0 to Day 28 when the patient will alive and free of invasive ventilation. In case of multiple periods of IMV during the first 28 days, the total duration of ventilation considered all periods of ventilation during the index admission. Patients who will die within 28 days or will be still on invasive ventilation after 28 days will score zero VFDs18	Day 28
Secondary	Occurrence of IMV (or ECMO) by day 28		Day 28
Secondary	Length of primary hospital stay		Throughout the trial
Secondary	Clinical failure by day 3 and day 7	Clinical failure will be defined as the occurrence of IMV/ECMO or vasopressor, or death	day 3 and day 7
Secondary	28-day ICU-free days		Day 28
Secondary	Days free of IMV/ECMO (number of days with NIAID-OS 1-6) at day 28		Day 28
Secondary	Duration of antibiotic therapy (days) at day 28		Day 28
Secondary	Hospital free days		Day 28
Secondary	Proportion of patients recovered	downward shift from screening of =2 points on the NIAID-OS or live discharge from hospital)	days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary	Proportion of patients worsening	upward shift from screening of at least >1 point of the NIAID-OS)	days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary	PO2/FiO2		days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary	All-cause mortality		Days 28 and 90
Secondary	Hospital re-admission by day 90 and 180		Days 90 and 180
Secondary	Time to discharge or to a NEWS of = 2 (for 24 hours), whichever occurs first		Day 28
Secondary	Change in inflammatory markers (LDH, CRP, ferritin; D-dimer, PCT) and cytokines		Days 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge]
Secondary	Change in quality of life using EuroQol-5-dimensions-5 levels (EQ-5D-5L) questionnaire	The EQ-5D-5L asks patients to indicate whether they have no, slight, moderate, severe, extreme problems on each of five dimensions of health: mobility; self-care; usual activities; pain/discomfort; anxiety/depression.	90±7 and 180±14 days
Secondary	Duration of IMV and/or ECMO at 90 and 180 days		Days 90 and 180
Secondary	ICU admission at 90 and 180 days		Days 90 and 180
Secondary	ICU length of stay at 90 and 180 days		Days 90 and 180
Secondary	Hospital length of stay at 90 and 180 days		Days 90 and 180
Secondary	Occurrence of infections at 90 and 180 days		Days 90 and 180