Evaluation of Pharmacokinetics, Safety, and Tolerability of Intravenous Zanamivir in Neonates and Infants Under 6 Months with Complicated Influenza

Trial ID: 2024-510663-34-00
Protocol: 200925
Sponsor: Glaxosmithkline Research & Development Limited

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Diseases & Conditions

Influenza

Objectives

The primary objective of this study is to characterize the **pharmacokinetics** of single and multiple doses of intravenous zanamivir in hospitalized neonates and infants under 6 months of age with confirmed complicated **influenza** infection. This is clinically relevant as understanding the pharmacokinetics in this vulnerable population can inform dosing regimens, ensuring both efficacy and safety of the treatment. The study aims to provide critical data on how the drug is absorbed, distributed, metabolized, and excreted in this specific age group, which is essential for optimizing therapeutic outcomes and minimizing potential adverse effects.

Participants

The clinical trial involves a total of **5 participants** who are hospitalised neonates and infants under 6 months of age diagnosed with **influenza**. The study population includes both male and female subjects, with a body weight of at least 1 kg. Participants were selected based on their confirmed influenza infection through a positive rapid molecular diagnostic test or a local quantitative RT-PCR test, with the potential for clinical improvement. The trial includes preterm neonates and infants, provided they have reached a post-menstrual age of at least 28 weeks. The legally acceptable representatives of the minors provided written informed consent for participation. The trial population is considered vulnerable due to the young age and health status of the participants. No specific lifestyle considerations such as diet or physical activity are mentioned for this study.

Plans and Procedures

The clinical trial is designed as an open-label, single-arm study to evaluate the pharmacokinetics, safety, and tolerability of **zanamivir** administered intravenously in neonates and infants under 6 months of age with confirmed complicated **influenza** infection. The trial aims to characterize the pharmacokinetics of single and multiple doses of zanamivir in this population. The study is expected to run from January 16, 2023, to December 9, 2026, with a maximum treatment period of 10 days for each participant. The trial will not be randomized or blinded, as it involves a single treatment arm.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and confirmed influenza infection. The inclusion criteria specify that participants must be neonates or infants under 6 months of age, with a body weight of at least 1 kg, and have a confirmed influenza infection through a positive rapid molecular diagnostic test or quantitative RT-PCR. The legally acceptable representative of the minors must provide written informed consent. Follow-up visits will be conducted to monitor the pharmacokinetics and safety of the treatment, with primary endpoints including the area under the serum concentration-time curve (AUC), maximum serum concentration (Cmax), clearance (CL), and terminal half-life (t1/2). The end-of-study visit will conclude the participant's involvement, assessing the overall safety and tolerability of the treatment.

Participant involvement is expected to last up to 10 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include adverse reactions to the treatment or withdrawal of consent by the legally acceptable representative. The study is categorized as a Phase IV trial, focusing on the post-marketing evaluation of zanamivir's use in a pediatric population. The trial is not considered low intervention, given the nature of the study population and the investigational use of the drug. The study will adhere to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

Treatment

The clinical trial involves the administration of **Dectova**, a 10 mg/mL **solution for infusion** containing the active substance **zanamivir**. This investigational medicinal product is provided in a pharmaceutical form suitable for **intravenous use**. The dosing regimen for this study specifies a maximum daily dose of 24 mg/kg, with a total maximum dose of 240 mg/kg over the course of the treatment. The treatment period is limited to a maximum of 10 days. The solution is administered to neonates and infants under 6 months of age who are hospitalized with confirmed complicated influenza infection. The study aims to evaluate the pharmacokinetics, safety, and tolerability of both single and multiple doses of intravenous zanamivir in this patient population.

In this open-label, single-arm study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the investigational product, Dectova. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The study is designed to explore clinical outcomes associated with the treatment, providing valuable data on the efficacy and safety of zanamivir in the specified patient group.

Efficacy

Efficacy in this clinical trial will be assessed through the evaluation of pharmacokinetic parameters of intravenous **zanamivir** in neonates and infants under 6 months of age with confirmed complicated influenza infection. The primary endpoints for efficacy assessment include the area under the serum concentration-time curve (AUC), maximum serum concentration (Cmax), clearance (CL), and terminal half-life (t1/2). These parameters will be measured to characterize the pharmacokinetics of single and multiple doses of the investigational product.

The collection and analysis of these pharmacokinetic parameters will be conducted using validated laboratory tests. The study is designed as an open-label, single-arm trial, allowing for the exploration of clinical outcomes alongside safety and tolerability assessments. The trial is set to run until December 2026, with recruitment having commenced in January 2023. The maximum treatment period for participants is 10 days, during which the pharmacokinetic data will be collected and analyzed to determine the efficacy of the treatment regimen.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age. 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.
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.
Weight. Body weight ≥1kg.
Sex. Male or female.
Informed Consent 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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Exclusion Criteria

Participants who are known or suspected to be hypersensitive to any component of the study medication.
Participants who, in the judgment of the investigator, are unlikely to complete the course of treatment due to their current disease process.
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.
Participants who require concurrent therapy with another anti influenza drug.
Participants who have participated in a study using an investigational drug within 30 days prior to Baseline.
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.
Patients undergoing treatment by Extracorporeal membrane oxygenation (ECMO) or hemofiltration.
Participants who are positive for SARS-CoV-2, as determined by a diagnostic test, at screening.