Reparixin in COVID-19 Pneumonia - Efficacy and Safety
Reparixin in COVID-19 Pneumonia - Efficacy and Safety
-  Phase 2 Study Objectives: efficacy and safety of of Reparixin treatment as compared to
 the control arm in adult patients with severe COVID-19 pneumonia

 -  Phase 3 Study Objectives: efficacy and safety of Reparixin treatment as compared to the
 control arm in adult patients with moderate or severe COVID-19 pneumonia
This clinical trial is an adaptive phase 2/3, randomized, controlled multicenter study on the
 efficacy and safety of Reparixin in the treatment of hospitalized patients with COVID-19
 pneumonia. 48 patients are planned to be enrolled in Phase 2 and an estimated total of 111
 patients are planned to be enrolled up to the end of Phase 3, with a randomization 2:1
 Reparixin vs Control (Standard of care).

 In the phase 2 segment of this study, patients are randomized 2:1 to Reparixin oral tablets
 1200 mg (Group 1, active treatment) or standard of care (Group 2, control arm). In case of
 worsening (e.g. need of ICU and/or mechanical ventilation) after the first 24hrs, patients
 are offered a rescue medication with no restriction from the sponsor and fully based on their
 physicians' judgement.

 In the phase 3 segment of this study, it is planned that patients are randomized 2:1 to
 Reparixin or standard of care. The Phase 3 design will be reassessed and decided based on the
 results of the Phase 2.
Inclusion Criteria:

 -  Phase 2 Inclusion Criteria:

 1. Age 18 to 90.

 2. Confirmed COVID-19 diagnosis

 3. At least one of the following: # Respiratory distress, RR ≥ 30 breaths/min
 without oxygen; # Partial arterial oxygen pressure (PaO2) / Fraction of
 inspiration O2 (FiO2) >100 <300mmHg

 (1mmHg = 0.133kPa). 4. Chest imaging confirms lung involvement and inflammation. 5.
 Inflammatory status as documented by at least one of the following: Lactate
 dehydrogenase (LDH) > normal range, C-reactive protein (CRP) ≥ 100mg/L or IL-6 ≥
 40pg/mL, serum ferritin ≥ 900ng/mL, XDP >20mcg/mL.

 -  Phase 3 Inclusion Criteria: Same as above; other criteria TBD based on Phase 2
 outcomes.

 Exclusion Criteria:

 • Phase 2/3 Exclusion Criteria:

 1. Cannot obtain informed consent.

 2. Severe hepatic dysfunction (Child Pugh score ≥ C, or AST> 5 times the upper limit);
 Severe renal dysfunction (estimated glomerular filtration rate ≤ 30mL / min / 1.73 m2)
 or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.

 3. Patients with hypersensitivity to ibuprofen or to more than one non steroidal
 anti-inflammatory drug or to more than one medication belonging to the class of
 sulfonamides (e.g. sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or
 celecoxib; hypersensitivity to sulphanilamide antibiotics alone, e.g.
 sulfamethoxazole, does not qualify for exclusion)

 4. Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous
 system bleeding, and nosebleeds within 1 month before enrollment.

 5. Pregnant and lactating women and those planning to get pregnant.

 6. Participated in other interventional clinical trials with investigational medicinal
 products, not considered suitable for this study by the researchers.

 7. At the time of enrollment, patients not in a clinical condition compatible with the
 oral administration of the study drug.