E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
Coronavirus disease 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
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows: 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 laboratory-confirmed 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 β-cyclodextrin sodium (SBECD) exposures (where possible) To provide data on use of medications other than RDV for treatment of 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 f) Cohort 8: < 12 years of age and weight at screening ≥ 40 kg 3) SARS-CoV-2 infection confirmed by PCR 4) Hospitalized and requiring medical care for 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 9) On renal replacement therapies (iHD, PD and CRRT)
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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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Summary of descriptive statistics for each 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Summary of descriptive statistics for each 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 | No |
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 | No |
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 | 16 |
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 | No |
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 |