E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 characterise the single and multiple dose to steady state pharmacokinetics of IV zanamivir in hospitalised neonates and infants under 6 months of age with influenza infection |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of IV zanamivir in hospitalised neonates and infants under 6 months of age with influenza infection
-To investigate clinical virology before, during and after the treatment of IV zanamivir
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Neonates and infants who are aged less than 6 months (corrected age) at the time of the informed consent signed by legally acceptable representative (LAR) of minors. Preterm neonates and infants will be eligible for inclusion but must have reached Post-Menstrual Age (PMA) of at least 28 weeks
2.Participants who are hospitalised with influenza infection, confirmed by a positive rapid molecular diagnostic test for influenza, or a local quantitative RT-PCR test and who must have a potential for improvement Subjects with negative rapid molecular test result suspected of having influenza can be enrolled following confirmatory testing by quantitative RT-PCR.
3.Body weight ≥ 1kg
4.Male or female.
5.Legally acceptable representative (LAR) of minors are willing and able to give written informed consent to participate in the study (or included as permitted by local regulatory authorities, IECs or local laws).
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E.4 | Principal exclusion criteria |
1.Participants who are known or suspected to be hypersensitive to any component of the study medication.
2.Participants with a disease process which is likely to be irreversible.
3.Liver function:
-Subjects who meet the following criteria at Baseline:
ALT ≥3xULN with Bilirubin ≥2xULN or Isolated bilirubin ≥ 2xULN and >50% direct bilirubin or ALT ≥5xULN
Inclusion of subjects with liver function tests that fall outside these criteria must be discussed and agreed with the medical monitor.
-Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of benign conditions such as Gilbert's syndrome). Inclusion of subjects with neonatal hyperbilirubinaemia may be considered if appropriately managed according to local guidelines and must be discussed with the medical monitor.
4.Participants who require concurrent therapy with another influenza antiviral drug. Antiviral treatment including oseltamivir are prohibited to be co-administered with IV zanamivir. (Section 6.4 in the protocol).
5.Prior/Concurrent Clinical Study Experience
Participants who have participated in a study using an investigational drug within 30 days prior to Baseline.
Other Exclusions
6.Child in care (CiC), as defined below:
-A child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.
-The definition of a CiC can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a CiC does not include a child who is adopted or has an appointed legal guardian.
7.Patients undergoing treatment by Extracorporeal membrane oxygenation (ECMO) or hemofiltration.
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E.5 End points |
E.5.1 | Primary end point(s) |
-Area under the serum concentration-time curve (AUC)
-Maximum serum concentration (Cmax)
-Clearance (CL)
-Terminal half-life (t1/2) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Four samples to be taken on Day 1: 25-30 min, 1-2 hours, 4-6 hours and 11-12 hours following start of the first dose and an additional pre-dose (trough) sample taken on Day 3 or Day 4 or Day 5. |
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E.5.2 | Secondary end point(s) |
-Adverse events
-Vital signs including heart rate, oxygen saturation, respiration rate and temperature
-Quantitative viral load over time and change from baseline
-Viral susceptibility to zanamivir at baseline, and if virus can be cultured, at subsequent timepoints during the study
-Nucleotide sequence analysis to determine emergence of resistance to zanamivir
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/a: As AEs occur
1/b: Daily
2/a, 2/b, 2/c: Baseline to 14 day post treatment, up to 24 days.
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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 | No |
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) | No |
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 | 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 | 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 | 9 |
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 | No |
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 | 3 |
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 | 3 |
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 |