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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
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; 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

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, 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.
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

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

Recruiting Locations

MedStar Health Research Institute-Hyatteville, Maryland
Washington, District of Columbia 20010
Contact:
Glenn Wortmann, MD

More Details

Status
Recruiting
Sponsor
Dompé Farmaceutici S.p.A

Study Contact

Sophie Toya, MD
+1 219 427 2474
sophie.toya@dompe.com

Detailed 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.

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.