Clinical trial NCT04494412: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Influenza, Human
Arthralgia
Keywords: Human influenza
Zanamivir
Pediatric
Hospitalized neonates and infants
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-07-31
Enrollment: 12
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, multi-center and single arm study
Primary purpose: TREATMENT

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.


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:

    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 (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

Primary outcomes:
measure: Area under the serum concentration-time curve (AUC) of zanamivir
timeFrame: Up to 12 hours after end of infusion on Day 1
measure: Maximum observed serum concentration (Cmax) of zanamivir
timeFrame: Up to 12 hours after end of infusion on Day 1
measure: Clearance (CL) in plasma following administration of zanamivir
timeFrame: 30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
measure: Terminal half-life (t1/2) of zanamivir
timeFrame: 30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Secondary outcomes:
measure: Number of participants with adverse event(s) (AE) and serious adverse event(s) (SAE)
timeFrame: From start of treatment (Day 1) up to Day 24
measure: Number of participants with abnormal findings in heart rate
timeFrame: From start of treatment (Day 1) up to Day 24
measure: Number of participants with abnormal findings in Oxygen Saturation
timeFrame: From start of treatment (Day 1) up to Day 24
measure: Number of participants with abnormal findings in respiration rate
timeFrame: From start of treatment (Day 1) up to Day 24
measure: Number of participants with abnormal findings in body temperature
timeFrame: From start of treatment (Day 1) up to Day 24
measure: Viral load over time after administration of zanamivir
timeFrame: Day 1 up to Maximum Day 24
measure: Change From Baseline in viral load after administration of zanamivir
timeFrame: Baseline (Day 1) and up to maximum Day 24
measure: Number of participants with phenotypic resistance
timeFrame: Up to Day 24
measure: Number of participants with genotypic resistance
timeFrame: Up to Day 24
measure: Number of participants with emergence of resistance to zanamivir
timeFrame: Up to Day 24
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Messina
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: