An Intravenous (IV) Zanamivir Pharmacokinetics (PK) Study in Hospitalized Neonates and Infants With Influenza Infection

NCT04494412 | Recruiting Phase 2 DMC

• 1 other identifier: 200925
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 9

Brief Summary

Influenza infection is an important public health priority, with seasonal outbreaks and pandemics causing considerable global morbidity and mortality. The PK, pharmacodynamics (PD), safety and efficacy of IV zanamivir have been evaluated in adults, adolescents and infants more than or equal to (\>=) 6 months of age with hospitalized influenza in the IV zanamivir global development program. However, antiviral treatment of neonates and infants under 6 months of age hospitalized with influenza infection remains a medical unmet need. Given the immaturity of the immune system at this age, there are no licensed influenza vaccines for children aged less than six months old. As a requirement of the Pediatric Investigation Plan European Union (EU), GlaxoSmithKline (GSK) will be conducting this open-label, multi-center, single arm, post-marketing authorization study to evaluate the PK and collect safety and tolerability information of IV zanamivir in hospitalized neonates and infants under 6 months of age with confirmed complicated influenza infection. The total duration of study participation for each participant will be up to 24 days with a study treatment period up to 10 days and 14 days of post-treatment follow up. However, for a given participant, the initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms, participant characteristics or virological tests as assessed by the investigator warrant further treatment. DECTOVA is a trademark of GlaxoSmithKline group of companies.

Conditions

Influenza, Human; Arthralgia

Keywords

Human influenza; Zanamivir; Pediatric; Hospitalized neonates and infants

Outcome Measures

Primary Outcomes (4)

• Area under the serum concentration-time curve (AUC) of zanamivir

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.

  Up to 12 hours after end of infusion on Day 1

• Maximum observed serum concentration (Cmax) of zanamivir

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.

  Up to 12 hours after end of infusion on Day 1

• Clearance (CL) in plasma following administration of zanamivir

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.

  30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5

• Terminal half-life (t1/2) of zanamivir

  Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.

  30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5

Secondary Outcomes (10)

• Number of participants with adverse event(s) (AE) and serious adverse event(s) (SAE)

  From start of treatment (Day 1) up to Day 24

• Number of participants with abnormal findings in heart rate

  From start of treatment (Day 1) up to Day 24

• Number of participants with abnormal findings in Oxygen Saturation

  From start of treatment (Day 1) up to Day 24

• Number of participants with abnormal findings in respiration rate

  From start of treatment (Day 1) up to Day 24

• Number of participants with abnormal findings in body temperature

  From start of treatment (Day 1) up to Day 24

Study Arms (1)

Hospitalized neonates and infants with influenza infection

EXPERIMENTAL

Preterm neonates and infants who have reached Post-Menstrual Age (PMA) of at least 28 weeks and have a confirmed complicated influenza infection will be included. Participants will receive daily IV infusion of zanamivir for up to 5 days. This initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms, participant characteristics or virological tests warrant further treatment. The initial dose of IV zanamivir will be determined by PMA/corrected age and body weight. The maintenance dose and interval between the initial dose and subsequent twice-daily maintenance dose will be further determined by Principal Investigator based on renal function.

Drug: Zanamivir

Interventions

Zanamivir DRUG

Zanamivir solution for infusion will be available as a 10 milligrams per milliliters (mg/mL) vial. DECTOVA is approved for age groups 6 months and above.

Also known as: DECTOVA

Hospitalized neonates and infants with influenza infection

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants who are hospitalized with influenza infection, confirmed by a positive rapid molecular diagnostic test for influenza, or a local quantitative Reverse transcriptase-polymerase chain reaction (RT-PCR) test and who must have a potential for improvement Participants with negative rapid molecular test result suspected of having influenza can be enrolled following confirmatory testing by quantitative RT-PCR.
• Participants with a high risk of altered oral drug absorption, represented by multi-organ dysfunction (dysfunction of at least 2 organs, as defined by the treating physician). (applicable only for Netherlands)
• Body weight \>=1 kilograms (kg).
• No gender restriction.
• 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, Independent Ethics Committees \[IECs\] or local laws).

You may not qualify if:

• Participants who are known or suspected to be hypersensitive to any component of the study medication.
• Participants with a disease process which is likely to be irreversible.
• Liver function:
• Participants who meet the following criteria at Baseline:
• Alanine transaminase (ALT) \>=3 times upper limit of normal (ULN) with bilirubin \>=2 times ULN
• or isolated bilirubin \>=2 times ULN and \>50 percent (%) direct bilirubin
• 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, organization, 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.
• Participants undergoing treatment by Extracorporeal membrane oxygenation (ECMO) or hemofiltration.
• Participants who are positive for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) as determined by a diagnostic test, at screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Florence, 50139, Italy

RECRUITING

GSK Investigational Site

Messina, Italy

RECRUITING

GSK Investigational Site

Milan, 20122, Italy

RECRUITING

GSK Investigational Site

Roma, 00165, Italy

RECRUITING

GSK Investigational Site

Bydgoszcz, 85-168, Poland

COMPLETED

GSK Investigational Site

Barcelona, 08950, Spain

RECRUITING

GSK Investigational Site

Madrid, 28046, Spain

RECRUITING

GSK Investigational Site

London, SW17 0QT, United Kingdom

RECRUITING

GSK Investigational Site

London, W2 1NY, United Kingdom

RECRUITING

MeSH Terms

Conditions

Influenza, Human; Arthralgia

Interventions

Zanamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Joint Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Sialic Acids; Neuraminic Acids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Sugars; Carbohydrates

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, multi-center and single arm study

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 31, 2020
• Study Start: November 21, 2022
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

ES (2); IT (4); GB (2); PL (1)