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Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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); 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; 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
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.
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
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).

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Reparixin + standard of care (SoC) 		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
    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.
    Other names:
    • Repertaxin L-lysine salt
Placebo Comparator
Placebo + standard of care (SoC) 		Placebo tablets are identical in appearance to the active formulation. Placebo was administered with the same treatment schedule.
  • Other: Placebo
    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.
    Other names:
    • Matched placebo

Recruiting Locations

More Details

NCT ID
NCT05254990
Status
Terminated
Sponsor
Dompé Farmaceutici S.p.A

Detailed Description

Multinational, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III trial. This study was conducted at 101 sites across 7 countries (Argentina, Australia, Austria, Germany, Italy, Turkey, and the United States [US]) that enrolled 414 male and female patients > 18 years of age, hospitalized for CAP (including COVID-19). Please note that of these 101 sites, only 74 had enrolled patients and, hence, have been reported on CT.gov. The maximum study duration for a participant was 180 days, which included screening (day -1 or 1), treatment (up to day 21), and follow-up period (up to day 180). Of the 414 patients enrolled, 409 (98.8%) were randomized 1:1 to receive investigational products (oral reparixin [N = 205] or matched placebo [N = 204], three times a day (TID), for up to 21 days. Randomization was stratified according to disease severity and site. Actually, 394 participants (96.3%)(oral reparixin [N = 201] or matched placebo [N = 193]) received at least 1 dose of the investigational product and hence were included in the FAS population. All the patients received the Standard of Care (SoC) 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. Of the randomized population (N = 409), 186 participants (45.5%) completed the study; 223 (54.5%) discontinued the study prematurely. The primary outcome was evaluated at day 28, while the secondary outcomes were scheduled to be evaluated from day 3 to day 180. An independent external data monitoring committee (DMC) oversaw the study and evaluated unblinded interim data for efficacy, futility, and safety. The interim efficacy analysis met the pre-specified criteria for futility and the DMC recommended early termination of the study. Based on the recommendation of the DMC, Dompé decided to terminate the study earlier than planned. The decision was not related to any safety concerns. Due to the early study termination and not reaching the planned enrollment target, the outcome measure analyses were conducted for descriptive purposes only.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.