E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 pneumonia |
Polmonite da COVID-19 |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 pneumonia |
Polmonite da COVID-19 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10047438 |
E.1.2 | Term | Viral infectious disorders |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- Phase 2 Study Objectives: efficacy and safety of Reparixin 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 severe COVID-19 pneumonia |
- Fase 2: valutare efficacia e sicurezza di Reparixin rispetto alla terapia standard in pazienti adulti con polmonite da COVID-19. - Fase 3: valutare efficacia e sicurezza di Reparixin rispetto alla terapia standard in pazienti adulti con polmonite da COVID-19. |
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E.2.2 | Secondary objectives of the trial |
Please refer to protocol |
Fare riferimento al protocollo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Phase 2 Inclusion Criteria: 1. Age 18 to 90. 2. Confirmed COVID-19 diagnosis 3. At least one of the following: 1. Respiratory distress, RR => 30 breaths/min without oxygen; 2. 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. |
- Phase 2 Inclusion Criteria: 1. Age 18 to 90. 2. Confirmed COVID-19 diagnosis 3. At least one of the following: 1. Respiratory distress, RR => 30 breaths/min without oxygen; 2. 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. |
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E.4 | Principal 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. |
- 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Phase 2 Primary Endpoint: Composite endpoint of clinical events (the patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason) - Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events (the patient dies or requires mechanical ventilation use and/or admission to ICU) |
- Phase 2 Primary Endpoint: Composite endpoint of clinical events (the patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason) - Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events (the patient dies or requires mechanical ventilation use and/or admission to ICU) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Secondary Endpoints: o Changes in clinical severity score (as recommended by the World Health Organization –WHO– for COVID studies) o Dyspnea severity (Liker scale and VAS scale) o Changes in body temperature o Changes in hematology test values o Duration and quantity of supplemental oxygen treatment o Incidence and duration of mechanical ventilation use o Incidence of intensive care unit (ICU) admission need o Lung damage extension changes from baseline (assessed by Chest CT or Rx) o Change from baseline in lung exudation degree (assessed by Chest CT or Rx) o PaO2 o SpO2 o Partial arterioral oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio o CRP o Hs-CRP; - Exploratory Endpoints (not mandatory): o Cytokine profile o Concentration of Reparixin in serum over time o SARS-CoV-2 virologic counts; - Safety Endpoints: o Adverse events o Serious adverse events |
- Endpoint secondari: o Livello di severità clinica o Severità della dispnea (Liker scale e VAS scale) o Temperatura corporea o Parametri ematochimici o Durata e quantità di ossigenoterapia supplementare o Incidenza e durata della ventilazione meccanica o Incidenza di accesso alla terapia intensiva o Modifiche del danno polmonare (valutato radiograficamente) o Modifiche del livello di essudazione polmonare (valutata radiograficamente) o PaO2 o SpO2 o PaO2/FiO2 o CRP o Hs-CRP; - Endpoint esploratori (non obbligatori): o Profilo citochinico o Concentrazione di Reparixin nel siero a tempi diversi o Conta virale di SARS-CoV-2; Endpoint di sicurezza: o Adverse events o Serious adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Terapia standard. |
Standard of care |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |