E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) |
Infezione da coronavirus 2019 (COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
Coronavirus disease 2019 (COVID-19) |
Infezione da coronavirus 2019 (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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
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 |
• To evaluate the safety and tolerability of remdesivir (RDV ) in participants with laboratory-confirmed COVID-19 aged 0 days to < 18 years. • To evaluate the pharmacokinetics (PK) of RDV in participants with laboratory-confirmed COVID-19 aged 0 days to < 18 years. |
• Valutare la sicurezza e la tollerabilità di remdesivir (RDV) in partecipanti affetti da COVID-19 confermata in laboratorio di età compresa tra 0 giorni e < 18 anni. • Valutare la farmacocinetica (PK) di RDV in partecipanti affetti da COVID-19 confermata in laboratorio di età compresa tra 0 giorni e < 18 anni. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of RDV in participants with laboratory-confirmed COVID-19 aged 0 days to < 18 years. • To determine the antiviral activity of RDV in participants with laboratoryconfirmed COVID-19 aged 0 days to < 18 years. • Change from baseline in oxygenation use. • Change from baseline in the use of mechanical ventilation or extra corporeal membrane oxygenation (ECMO). • To evaluate clinical improvement using the PEWS scale in participants with laboratory-confirmed COVID-19 aged 0 days to < 18 years. • Determine sulfobutylether ß-cyclodextrin sodium (SBECD) exposures (where possible). • To provide data on use of medications other than RDV for treatment of COVID-19. |
• Valutare l’efficacia di RDV in partecipanti affetti da COVID-19 confermata in laboratorio di età compresa tra 0 giorni e < 18 anni • Determinare l'attività antivirale di RDV in partecipanti affetti da COVID-19 confermata in laboratorio di età compresa tra 0 giorni e < 18 anni • Variazioni rispetto al basale nell’uso dell’ossigenazione • Variazioni rispetto al basale nell’utilizzo della ventilazione meccanica o dell’ossigenazione extracorporea a membrana (ECMO) • Valutare il miglioramento clinico utilizzando la scala del punteggio di allarme precoce pediatrico (PEWS) in partecipanti affetti da COVID-19 confermata in laboratorio di età compresa tra 0 giorni e < 18 anni • Determinare le esposizioni alla solfobutiletere-beta-ciclodestrina sodica (SBECD) (ove possibile) • Fornire dati sull’utilizzo di farmaci diversi da RDV per il trattamento di COVID-19 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Willing and able to provide assent or a parent or legal guardian willing and able to provide written informed consent (participants < 18 years of age, where locally and nationally approved) prior to performing study procedures. 2) Aged < 18 years of age who meet one of the following weight criteria (where permitted according to local law and approved nationally and by relevant institutional review board [IRB] or independent ethics committee [IEC]). a) Cohort 1: = 12 years to < 18 years of age and weight at screening = 40 kg b) Cohorts 2-4: = 28 days to < 18 years of age and weight at screening =3 kg and < 40 kg c) Cohort 5: = 14 days to <28 days of age, gestational age > 37 weeks and weight at screening = 2.5 kg d) Cohort 6: 0 days to < 14 days of age, gestational age > 37 weeks and birth weight of = 2.5 kg e) Cohort 7: 0 days to < 56 days of age, gestational age = 37 weeks and birth weight of = 1.5 kg 3) SARS-CoV-2 infection confirmed by PCR 4) Hospitalized and requiring medical care for COVID-19 |
1) Soggetti disposti e in grado di fornire l’assenso o un genitore o tutore legale disposto e in grado di fornire il consenso informato scritto prima di eseguire le procedure dello studio. 2) Età < 18 anni, che soddisfano uno dei seguenti criteri di peso. a) Coorte 1: da = 12 anni a < 18 anni di età e peso allo screening = 40 kg b) Coorti 2-4: da = 28 giorni a < 18 anni di età e peso allo screening da = 3 kg a < 40 kg c) Coorte 5: da = 14 giorni a < 28 giorni di età, età gestazionale > 37 settimane e peso allo screening = 2,5 kg d) Coorte 6: da 0 giorni a < 14 giorni di età, età gestazionale > 37 settimane e peso alla nascita = 2,5 kg e) Coorte 7: da 0 giorni a < 56 giorni di età, età gestazionale = 37 settimane e peso alla nascita = 1,5 kg 3) Infezione da SARS-CoV-2 confermata da PCR 4) Ricoverati in ospedale e che richiedono cure mediche per COVID-19 |
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E.4 | Principal exclusion criteria |
1) Concurrent treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 < 24 hours prior to study drug dosing 2) ALT or AST > 5 X ULN 3) eGFR < 30 mL/min using Schwartz formula for participants = 1 year of age 4)Creatinine above thresholds as described in (see table in Page 27) Protocol for < 1 year of age 5) If < 28 days of age, any major congenital renal anomaly 6) If < 24 hours of age, Apgar score < 5 at 10 minutes 7) Known hypersensitivity to the study drug, the metabolites, or formulation excipient |
1) Trattamento concomitante con altri agenti con effettiva o possibile attività antivirale diretta contro SARS-CoV-2 < 24 ore prima della dose del farmaco sperimentale 2) ALT o AST > 5 x il limite superiore della norma (ULN) 3) Velocità di filtrazione glomerulare stimata (eGFR) < 30 ml/min utilizzando la formula di Schwartz per i partecipanti = 1 anno di età 4) Creatinina superiore alle soglie della tabella riportata di seguito per < 1 anno di età 5) Se < 28 giorni di età, qualsiasi anomalia renale congenita maggiore 6) Se < 24 ore di età, indice di Apgar < 5 a 10 minuti 7) Ipersensibilità nota verso il farmaco sperimentale, i metaboliti o l’eccipiente della formulazione |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The proportion of participants with treatment-emergent adverse events (TEAEs). • The proportion of participants with treatment-emergent graded laboratory abnormalities. • PK assessed by plasma concentrations of RDV and metabolites. |
• Incidenza degli eventi avversi (EA) emergenti dal trattamento • Incidenza emergente dal trattamento dei valori clinici anomali di laboratorio • PK valutata mediante concentrazioni plasmatiche di RDV e metaboliti |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Summary of descriptive statistics for each endpoint |
Riassunto delle statistiche descrittive di ciascun endpoint |
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E.5.2 | Secondary end point(s) |
• Oxygen usage and ventilation modality and settings • Clinical improvement based on scoring using the 7-point Ordinal Scale • Time (days) to discharge from hospital • Days to the first confirmed negative PCR result, where confirmed is defined as 2 consecutive negative PCR results • Change from baseline in SARS-CoV-2 viral load up to Day 10 or up to the first confirmed negative PCR result (whichever comes first) • Bilirubin concentrations in < 14-day-old participants • Clinical improvement based on scoring using the PEWS Improvement Scale Plasma concentrations of SBECD (where possible) • The proportion of participants with concomitant use of medications other than RDV for treatment of COVID-19 |
• Necessità di ossigeno e ventilazione meccanica • Punteggio clinico su Scala ordinale a 7 punti • Tempo (giorni) alla dimissione dall’ospedale • Giorni al primo risultato negativo alla PCR confermato, dove per “confermato” si intendono 2 risultati negativi alla PCR consecutivi • Variazione rispetto al basale nel carico virale di SARS-CoV-2 fino al Giorno 10 o fino al primo risultato negativo alla PCR confermato (a seconda di quale evento si verifichi prima) • Concentrazioni di bilirubina nei partecipanti < 14 giorni • Miglioramento clinico basato sul punteggio della Scala di miglioramento PEWS • Proporzione di partecipanti con uso concomitante di farmaci diversi da RDV per il trattamento di COVID-19 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Summary of descriptive statistics for each endpoint |
Riassunto delle statistiche descrittive di ciascun endpoint |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Italy |
Spain |
United Kingdom |
United States |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |