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

Primary Purpose

Influenza, Human, Arthralgia

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Zanamivir
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza, Human focused on measuring Human influenza, Zanamivir, Pediatric, Hospitalized neonates and infants

Eligibility Criteria

undefined - 6 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 PMA of at least 28 weeks.
  • 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.
  • 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).

Exclusion criteria:

  • 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:

      1. Alanine transaminase (ALT) >=3 times upper limit of normal (ULN) with bilirubin >=2 times ULN
      2. or isolated bilirubin >=2 times ULN and >50 percent (%) direct bilirubin
      3. or ALT >=5 times ULN Inclusion of participants 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 participants with neonatal hyperbilirubinemia 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 influenza antiviral drug. Antiviral treatment including oseltamivir are prohibited to be co-administered with IV zanamivir.
  • 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.

Sites / Locations

  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hospitalized neonates and infants with influenza infection

Arm Description

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.

Outcomes

Primary Outcome Measures

Area under the serum concentration-time curve (AUC) of zanamivir
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Maximum observed serum concentration (Cmax) of zanamivir
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Clearance (CL) in plasma following administration of zanamivir
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Terminal half-life (t1/2) of zanamivir
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.

Secondary Outcome Measures

Number of participants with adverse event(s) (AE) and serious adverse event(s) (SAE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.
Number of participants with abnormal findings in heart rate
Number of participants with abnormal findings for heart rate will be assessed.
Number of participants with abnormal findings in Oxygen Saturation
Number of participants with abnormal findings for Oxygen Saturation will be assessed.
Number of participants with abnormal findings in respiration rate
Number of participants with abnormal findings for respiration rate will be assessed.
Number of participants with abnormal findings in body temperature
Number of participants with abnormal findings for body temperature will be assessed.
Viral load over time after administration of zanamivir
Nasopharyngeal swab samples will be collected for assessing quantitative viral load.
Change From Baseline in viral load after administration of zanamivir
Nasopharyngeal swab samples will be collected for assessing quantitative viral load.
Number of participants with phenotypic resistance
Nasopharyngeal swab samples will be collected for assessing phenotypic resistance.
Number of participants with genotypic resistance
Nasopharyngeal swab samples will be collected for assessing genotypic resistance.
Number of participants with emergence of resistance to zanamivir
Nucleotide sequence analysis will be carried out to determine emergence of resistance to zanamivir.

Full Information

First Posted
July 15, 2020
Last Updated
February 16, 2023
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT04494412
Brief Title
An Intravenous (IV) Zanamivir Pharmacokinetics (PK) Study in Hospitalized Neonates and Infants With Influenza Infection
Official Title
An Open Label, Single Arm Study to Evaluate Single and Multiple Dose Pharmacokinetics, Safety and Tolerability, and to Explore Clinical Outcomes of Treatment With Intravenous (IV) Zanamivir in Neonates and Infants Under 6 Months of Age With Confirmed Complicated Influenza Infection
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 21, 2022 (Actual)
Primary Completion Date
December 11, 2023 (Anticipated)
Study Completion Date
December 11, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Human, Arthralgia
Keywords
Human influenza, Zanamivir, Pediatric, Hospitalized neonates and infants

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label, multi-center and single arm study
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hospitalized neonates and infants with influenza infection
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Zanamivir
Other Intervention Name(s)
DECTOVA
Intervention Description
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.
Primary Outcome Measure Information:
Title
Area under the serum concentration-time curve (AUC) of zanamivir
Description
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Time Frame
Up to 12 hours after end of infusion on Day 1
Title
Maximum observed serum concentration (Cmax) of zanamivir
Description
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Time Frame
Up to 12 hours after end of infusion on Day 1
Title
Clearance (CL) in plasma following administration of zanamivir
Description
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Time Frame
30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Title
Terminal half-life (t1/2) of zanamivir
Description
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Time Frame
30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Secondary Outcome Measure Information:
Title
Number of participants with adverse event(s) (AE) and serious adverse event(s) (SAE)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.
Time Frame
From start of treatment (Day 1) up to Day 24
Title
Number of participants with abnormal findings in heart rate
Description
Number of participants with abnormal findings for heart rate will be assessed.
Time Frame
From start of treatment (Day 1) up to Day 24
Title
Number of participants with abnormal findings in Oxygen Saturation
Description
Number of participants with abnormal findings for Oxygen Saturation will be assessed.
Time Frame
From start of treatment (Day 1) up to Day 24
Title
Number of participants with abnormal findings in respiration rate
Description
Number of participants with abnormal findings for respiration rate will be assessed.
Time Frame
From start of treatment (Day 1) up to Day 24
Title
Number of participants with abnormal findings in body temperature
Description
Number of participants with abnormal findings for body temperature will be assessed.
Time Frame
From start of treatment (Day 1) up to Day 24
Title
Viral load over time after administration of zanamivir
Description
Nasopharyngeal swab samples will be collected for assessing quantitative viral load.
Time Frame
Day 1 up to Maximum Day 24
Title
Change From Baseline in viral load after administration of zanamivir
Description
Nasopharyngeal swab samples will be collected for assessing quantitative viral load.
Time Frame
Baseline (Day 1) and up to maximum Day 24
Title
Number of participants with phenotypic resistance
Description
Nasopharyngeal swab samples will be collected for assessing phenotypic resistance.
Time Frame
Up to Day 24
Title
Number of participants with genotypic resistance
Description
Nasopharyngeal swab samples will be collected for assessing genotypic resistance.
Time Frame
Up to Day 24
Title
Number of participants with emergence of resistance to zanamivir
Description
Nucleotide sequence analysis will be carried out to determine emergence of resistance to zanamivir.
Time Frame
Up to Day 24

10. Eligibility

Sex
All
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 PMA of at least 28 weeks. 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). Exclusion criteria: 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 or ALT >=5 times ULN Inclusion of participants 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 participants with neonatal hyperbilirubinemia may be considered if appropriately managed according to local guidelines and must be discussed with the medical monitor (Not-applicable for Great Britain). 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Saskia de N Wildt
Facility Name
GSK Investigational Site
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Piotr Korbal
Facility Name
GSK Investigational Site
City
Esplugues De Llobregat. Barcelona
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Mónica Balaguer Gargallo
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Cristina Calvo Rey
Facility Name
GSK Investigational Site
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Clare Webster
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Soumendu Manna

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Learn more about this trial

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

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