Reparixin as add-on Therapy to Standard of Care to Limit Disease Progression in Adult Patients With COVID-19.

Sponsor

Dompé Farmaceutici S.p.A (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05254990

Collaborator

(none)

474

Enrollment

Locations

Arms

18.9

Anticipated Duration (Months)

47.4

Patients Per Site

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary objective:

To evaluate the efficacy of oral reparixin versus standard care alone in limiting disease progression in adult patients hospitalised for 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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Pneumonia Sars-CoV-2 Infection	Drug: Reparixin Other: Placebo	Phase 3

Detailed Description

Multinational, multicentre, randomised, double-blind, placebocontrolled, parallel-group, phase III trial. It will enrol 450 male and female patients >18 years, hospitalised for 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 medications, as per local standard therapy at the trial site and in line with international guidelines. Primary and secondary efficacy outcomes will be evaluated up to day 28. Additional follow-up information on the patient clinical condition and survival will be collected at day 60+/-7. An independent external data monitoring committee (DMC) will oversee the study and evaluate unblinded interim data for efficacy, futility, and safety.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

474 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

male and female patients >18 years, hospitalised for COVID-19, will be 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.male and female patients >18 years, hospitalised for COVID-19, will be 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.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Reparixin 1200 mg TID as add-on Therapy to Standard of Care to Limit Disease Progression in Hospitalised Adult Patients With COVID-19. A Multinational, Randomised, Double Blinded, Placebo-controlled, Parallel-group Phase III Trial.

Actual Study Start Date :

Apr 6, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reparixin + standard of care Reparixin 600 mg tablets, administered orally at the dose of 1200 mg TID (2 tablets TID) as add-on therapy to standard of care. Administered up to 21 days (or until IMV/ECMO, if any)	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 . Other Names: Repertaxin L-lysine salt
Placebo Comparator: Placebo + standard of care Placebo tablets. Administered orally with the same schedule as reparixin.	Other: Placebo Administered orally three times a day (TID) as add-on therapy to standard of care up to 21 days. Other Names: Matched placebo

Arm

Intervention/Treatment

Experimental: Reparixin + standard of care

Reparixin 600 mg tablets, administered orally at the dose of 1200 mg TID (2 tablets TID) as add-on therapy to standard of care. Administered up to 21 days (or until IMV/ECMO, if any)

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 .

Other Names:

Repertaxin L-lysine salt

Placebo Comparator: Placebo + standard of care

Placebo tablets. Administered orally with the same schedule as reparixin.

Other: Placebo

Administered orally three times a day (TID) as add-on therapy to standard of care up to 21 days.

Other Names:

Matched placebo

Outcome Measures

Primary Outcome Measures

Proportion of patients requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by day 28 [NIAID-OS 7]. [Day 28]
NIAID-OS = National Institute of Allergy and Infectious Disease - Ordinal Scale

Secondary Outcome Measures

Proportion of patients recovered (downward shift from screening of ≤2 points on the NIAID-OS or live discharge from hospital) [Day 28]
Proportion of patients worsening (upward shift from screening of at least >1 point of the NIAID-OS) [Day 28]
Number of ventilatory-free days (VFDs) [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 VFDs
Incidence of secondary infections [Day 28]
Microbiologically confirmed infections, other than COVID-19, that will develop to day 28 and do not appear to be incubating at the time of inclusion
All-cause mortality [Day 28]
ICU-free days [Day 28]
Days free of IMV/ECMO (number of days with NIAID-OS 1-5) [Day 28]
Hospital free days [Day 28]
Proportion of patients recovered (downward shift from screening of ≤2 points on the NIAID-OS or live discharge from hospital) [day 3, 7 ±1, 14±2, 21±2 or at hospital discharge]
Proportion of patients worsening (upward shift from screening of at least >1 point of the NIAID-OS) [day 3, 7 ±1, 14±2, 21±2 or at hospital discharge]
PO2/FiO2 [day 3, 7 ±1, 14±2, 21±2, 28±2 or at hospital discharge]
All-cause mortality [day 14 and day 60]
Time to discharge or to a NEWS of ≤ 2 (for 24 hours), whichever occurs first [Day 28]
Change in inflammatory markers (LDH, CRP, ferritin; D-dimer) and cytokines [Baseline, day 21 (or end of treatment)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Informed consent signed
Male and female ≥18 years old;
Patients hospitalized for SARS-CoV-2 infection Reverse Transcriptase-Polymerase Chain Reaction-confirmed in the previous 10 days;
Need for non-invasive supplemental oxygen (NIAID-OS 5-6);
Radiological infiltrates by chest imaging;
Peripheral Capillary Oxygen Saturation (SpO2) <94% at room air, or PaO2/FiO2 (Partial pressure of oxygen / Fraction of inspiration oxygen) <300;
At least one inflammatory marker above Upper Limit of Normal (ULN) (Lactate dehydrogenase or LDH; C-Reactive Protein or CRP; ferritin; D-dimer);
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 Investigational Medicinal Product 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.

Exclusion Criteria:

Treatment with IMV or ECMO (NIAID-OS 7);
Hepatic dysfunction: Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 5 ULN; history of chronic hepatic disease (defined with Child-Pugh score B or C);
Renal dysfunction: estimated glomerular filtration rate (Estimated Glomerular Filtration Rate, Modification of Diet in Renal Disease study equation) <50 mL/min/1.73 m2, or need for haemodialysis or hemofiltration;
PaO2/FiO2 ratio < 100 mmHg;
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:
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)
lactase deficiency, galactosemia or glucose-galactose malabsorption
gastrointestinal bleeding or perforation due to previous NSAIDs therapy or recurrent peptic ulcer/haemorrhage
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;
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	Country	Postal Code
1	Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate (CEMICEF)	Ferrara	Italy	44121
2	IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza	Milan	Italy	20089
3	IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione	Milan	Italy	20132
4	ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive	Milan	Italy	20142
5	ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive	Milan	Italy	20162
6	A.O.U. Federico II Malattie Infettive del Policlinico Federico II	Milan	Italy	80131
7	Università della Campania "Luigi Vanvitelli" Dipartimento di Malattie Infettive	Milan	Italy	80133
8	ASST-Monza Ospedale San Gerardo Malattie Infettive	Monza	Italy	20900
9	Struttura semplice di terapia demi-intensiva respiratoria S.C. di pneumologia AO IRCCS Santa Maria Nuova	Reggio Emilia	Italy	42123
10	UO Complessa di Pneumologia - Ospedale di Rovigo	Rovigo	Italy	45100