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

NCT05254990 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: REP03212021-006951-32
• Study Type: interventional
• Target: 414
• Locations: 6 countries
• Sites: 70

Brief Summary

Primary objective: \- To compare the efficacy of reparixin vs. placebo in the proportion of patients dead or requiring IMV (or ECMO) by Day 28. Key secondary objectives:

• To compare the efficacy of reparixin vs placebo in all-cause mortality at day 180.
• To compare the efficacy of reparixin vs placebo in proportion of patients alive and discharged at day 28
• To compare the efficacy of reparixin vs placebo in ventilatory-free days at day 28.
• To compare the efficacy of reparixin vs placebo in proportion of patients with IMV (or ECMO) by day 28.
• To compare the efficacy of reparixin vs placebo in length of primary hospital stay. Other efficacy objectives \- To compare the efficacy of reparixin vs placebo on several disease severity/progression measures including recovery, ventilatory free days and mortality. Safety objectives: \- To evaluate safety and tolerability of oral reparixin versus placebo in the specific clinical setting.

Conditions

Infectious Pneumonia; Severe COVID-19

Keywords

COVID-19; SARS-CoV-2; Infectious pneumonia acquired in the community (CAP)

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Dead or Requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 [NIAID-OS 7].

  The primary endpoint was based on NIAID-OS ordinal scale (National Institute of Allergy and Infectious Disease) with score OS 7 which means patients "hospitalized, on invasive mechanical ventilation or ECMO". The scores on this scale of Disease severity range from OS 1 (best outcome) to OS 8 (worst outcome). NIAID-OS (National Institute of Allergy and Infectious Disease Ordinal Scale) SCORE Descriptor: * OS 1 Not hospitalized, no limitations on activities; * OS 2 Not hospitalized, limitation on activities and/or requiring home O2; * OS 3 Hospitalized, no supplemental O2 - no longer requires ongoing medical care; * OS 4 Hospitalized, no supplemental O2 - requiring ongoing medical care; * OS 5 Hospitalized, requiring supplemental O2; * OS 6 Hospitalized, on non-invasive ventilation or high-flow oxygen devices; * OS 7 Hospitalized, on invasive mechanical ventilation or ECMO; * OS 8 Death;

  Day 28

Secondary Outcomes (27)

• All-cause Mortality by Day 180

  Day 180

• Proportion of Patients Alive and Discharged From the Hospital by Day 28

  Day 28

• Ventilatory-free Days (VFD) by Day 28

  Day 28

• Proportion of Patients With IMV (or ECMO) by Day 28

  Day 28

• Length of Primary Hospital Stay (in Days)

  Day 180

Study Arms (2)

Reparixin + standard of care (SoC)

EXPERIMENTAL

Reparixin was administered orally at the dose of 1200 mg (2 x 600 mg tablets) TID (6 tablets daily) for up to 21 days. The three daily doses were administered maintaining an interval between doses of about 8 hours.

Drug: Reparixin

Placebo + standard of care (SoC)

PLACEBO COMPARATOR

Placebo tablets are identical in appearance to the active formulation. Placebo was administered with the same treatment schedule.

Other: Placebo

Interventions

Reparixin DRUG

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 was taken with a glass of water (about 250 mL) and a light meal or snack, as it was preferable that reparixin was taken with food. However, If the patient was unwilling or unable to administer oral tablets, investigator could decide a nasogastric tube as an alternative route.

Also known as: Repertaxin L-lysine salt

Reparixin + standard of care (SoC)

Placebo OTHER

Administered orally three times a day (TID) as add-on therapy to standard of care (SoC) up to 21 days. Placebo was taken with a glass of water (about 250 mL) and a light meal or snack, as it was preferable that placebo was taken with food. However, if the patient was unwilling or unable to administer oral tablets, investigator could decide a nasogastric tube as an alternative route.

Also known as: Matched placebo

Placebo + standard of care (SoC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent signed
• Male and female ≥18 years old;
• Patients hospitalized for clinically suspected CAP, defined as the occurrence of (within 48h from hospital admission):
• at least 1 of the following signs/symptoms: dyspnea, cough, purulent sputum, crackles (rales) and/or rhonchi
• body temperature \> 38°C or \<36°C (before or during admission) or leucocytosis (\> local ULN)
• new/increased pulmonary infiltrate(s) by chest imaging
• Need for non-invasive supplemental oxygen (NIAID-OS 5-6);
• SpO2 \<92% at room air, or PaO2/FiO2 (or SpO2/FiO2) \<300;
• 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:
• 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
• 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
• A male sexual partner who agrees to use a male condom with spermicide
• 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.

You may not qualify if:

• Treatment with IMV or ECMO (NIAID-OS 7);
• Hepatic dysfunction: ALT or AST \> 5 ULN; history of chronic hepatic disease (defined with Child-Pugh score B or C);
• Renal dysfunction: estimated glomerular filtration rate (eGFR, MDRD) \<50 mL/min/1.73 m2, or need for haemodialysis or hemofiltration;
• 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)
• Treatment with prohibited medication within 5 half-lives, and inability to stop during treatment period;
• Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening
• History of:
• lactase deficiency, galactosemia or glucose-galactose malabsorption
• gastrointestinal bleeding or perforation due to previous NSAIDs therapy or recurrent peptic ulcer/haemorrhage
• allergy to reparixin or any component of the IMP formulation
• Active bleeding or bleeding diathesis (excluding menses), prior intracranial haemorrhage
• Participation in other interventional clinical trials
• Clinical condition not compatible with oral administration of the study drug
• Pregnancy:
• positive or missing pregnancy test before first drug intake or day 1;

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (74)

MD Banner University Medical Center /Arizona University

Tucson, Arizona, 85719, United States

Location

UCI Health

Orange, California, 92868, United States

Location

Denver Health

Denver, Colorado, 80204, United States

Location

MedStar Health Research Institute-Hyatteville, Maryland

Washington D.C., District of Columbia, 20010, United States

Location

Research Alliance Inc.

Clearwater, Florida, 33756, United States

Location

University of Florida-Jacksonville

Jacksonville, Florida, 32209, United States

Location

Emory Johns Creek Hospital

Atlanta, Georgia, 30342, United States

Location

Augusta University Health - Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Methodist Hospital

Gary, Indiana, 46404, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

MidMichigan Medical Center - Midland

Midland, Michigan, 48670, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

University Hospital - MU Healthcare

Columbia, Missouri, 65212, United States

Location

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Research St Louis

St Louis, Missouri, 63141, United States

Location

NYU Langone Hospital-Brooklyn

Brooklyn, New York, 11220, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Duke University Hospital

Durham, North Carolina, 27708, United States

Location

Oregon Health & Science University (OHSU) - Pulmonary Clinic

Portland, Oregon, 97239, United States

Location

Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Baptist Hospitals of Southeast Texas

Beaumont, Texas, 77701, United States

Location

Texoma Medical Center

Denison, Texas, 75020, United States

Location

University of Utah Hospitals & Clinics

Salt Lake City, Utah, 84108, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22903, United States

Location

Virginia Commonwealth University Health

Richmond, Virginia, 23298, United States

Location

Hospital Interzonal General de Agudos Dr Jose Penna

Bahía Blanca, Buenos Aires, 8001, Argentina

Location

Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1181, Argentina

Location

Hospital Italiano de La Plata

La Plata, Buenos Aires, 1900, Argentina

Location

Instituto Medico Platense

La Plata, Buenos Aires, 1900, Argentina

Location

Clinica Independencia

Munro, Buenos Aires, 1605, Argentina

Location

Sanatorio Finochietto

Ciudad Autonoma de Buenos Aire, Buenos Aires F.D., 1187, Argentina

Location

Sanatorio de la Cañada

Villa María, Córdoba Province, 5900, Argentina

Location

Sanatorio Britanico S.A.

Rosario, Santa Fe Province, 2000, Argentina

Location

Clinica Adventista Belgrano

Buenos Aires, 1430, Argentina

Location

Sanatorio Agote

Buenos Aires, C1425 EOE, Argentina

Location

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, 1280, Argentina

Location

Nuevo Hospital San Roque

Córdoba, 5000, Argentina

Location

Sanatorio Privado de la Cañada - Cordoba

Córdoba, 5000, Argentina

Location

Sanatorio Privado Duarte Quiroz De Clinica Colombo SA

Córdoba, 5000, Argentina

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Mater Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Kepler Universitatsklinikum Med Campus III

Linz, 4020, Austria

Location

KH der Barmherzigen Brüder Linz

Linz, 4020, Austria

Location

Medizinische Universitaet Wien, Medizinische Klinik I, Abteilung für Infektionskrankheiten und Tropenmedizin

Vienna, 1090, Austria

Location

Klinik Favoriten (Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital mit Gottfried von Preyer'schem Kinderspital)

Vienna, 1100, Austria

Location

Helios Hamper-Klinikum Dachau

Dachau, Bavaria, 85221, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 01307, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Südniedersachsen, 37075, Germany

Location

ASST - Ospedale Papa Giovanni XXIII - UOC Pneumologia

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Universitaria di Bologna - Ospedale Sant'Orsola

Bologna, 40138, Italy

Location

Campus Universitario "Salvatore Venuta", Complesso Clinico, Padiglione B, 8° livello, Pneumologia

Catanzaro, 88100, Italy

Location

University Of Genoa - Ospedale Policlinico IRCCS San Martino di Genova

Genova, 16132, Italy

Location

IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza

Milan, 20089, Italy

Location

IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione

Milan, 20132, Italy

Location

ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive

Milan, 20142, Italy

Location

Università degli Studi di Milano-Ospedale "L.Sacco" Polo Universitario - ASST Fatebenefratelli Sacco

Milan, 20157, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive

Milan, 20162, Italy

Location

ASST-Monza Ospedale San Gerardo Malattie Infettive

Monza, 20900, Italy

Location

Clinica Pneumologica "L. Vanvitelli" - Osp Monaldi

Naples, 80131, Italy

Location

AOUP "P.Giaccone" - UOC Pneumologia

Palermo, 90127, Italy

Location

Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia, Dipartimento di Scienze Mediche e Malattie Infettive

Pavia, 27100, Italy

Location

Struttura semplice di terapia demi-intensiva respiratoria S.C. di pneumologia AO IRCCS Santa Maria Nuova

Reggio Emilia, 42123, Italy

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Dicle University, Medical Faculty

Diyarbakır, 21280, Turkey (Türkiye)

Location

Gaziantep Universitesi Sahinbey Arastirma Ve Uygulama Hastanesi

Gaziantep, 27310, Turkey (Türkiye)

Location

Acibadem Atakent Hospital

Istanbul, 34303, Turkey (Türkiye)

Location

Dokuz Eylul University Faculty of Medicine

Izmir, 35340, Turkey (Türkiye)

Location

Kayseri State Hospital

Kayseri, 38039, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

Inonu Uni.Med.Faculty

Malatya, 44100, Turkey (Türkiye)

Location

Related Publications (1)

• Truwit JD, Fleming K, Nanchal RS. Empowering Respiratory Therapists to Restrict Nebulized 3% Saline and N-Acetylcysteine During Mechanical Ventilation. Respir Care. 2025 Aug;70(8):937-945. doi: 10.1089/respcare.12586. Epub 2025 Feb 24.

  PMID: 40028879 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

reparixin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

An interim analysis conducted on the first 250 participants who had reached day 28 or died or experienced IMV or ECMO by day 28 indicated that the primary efficacy endpoint met the pre-specified criteria for futility. Based on the recommendation of the DMC, Dompé decided to terminate the study early for futility. The decision was not related to any safety concerns.

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé Farmaceutici S.p.A.

clinicaltrials@dompe.com

+39 02 583831

Study Officials

• Giovanni Landoni, MD

  IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The appearance, including packaging and labelling, of the investigational product tablets (reparixin and placebo) were identical in appearance such that the actual treatment could not be identified. The investigational product identity remained unknown to participants, site staff, CRO and Dompé personnel until after the study was completed and the database was unblinded (5 February 2025).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: male and female patients \>18 years, hospitalised for COVID-19, were 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.

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: February 24, 2022
• Study Start: April 27, 2022
• Primary Completion: July 29, 2024
• Study Completion: September 27, 2024
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-02

Locations

AR (14); US (28); AU (3); DE (3); IT (14); TU (8)