PrimaryTo characterise the single and multiple dose to steady state pharmacokinetics of IV zanamivirin hospitalised neonates and infants under 6 months of age with influenza infection.SecondaryTo evaluate the safety and tolerability of IV zanamivir…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Area under the serum concentration-time curve (AUC)
Maximum serum concentration (Cmax)
Clearance (CL)
Terminal half-life (t1/2)
Secondary outcome
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
Background summary
Influenza infection continues to be an important public health priority, with
seasonal outbreaks and pandemics causing considerable global morbidity and
mortality. It is estimated that, each year around the world seasonal influenza
accounts for 3-5 million cases of severe illness and 290,000 to 650,000
respiratory deaths.
Between 3% and 11% of children aged < 2 years in developed countries acquire
influenza-associated illness every year, creating a major burden on both
primary and secondary care services.
Most of the clinical experience with IV zanamivir administration in paediatric
population comes from the paediatric cohort of the phase II study (NAI113678,
Bradley, 2017), in which 71 subjects 6 months - <18 years were included.
Paediatric and adolescent subjects (6 months - 18 years of age) received an
age-adjusted, weight-based dose intended to provide systemic exposure
comparable to 600 mg in adults. The dosage adjustments in paediatric subjects
based on age, weight and renal function resulted in areas under the curves
(AUCs) similar to adults. In the paediatric cohort, the safety profile of IV
zanamivir was consistent with that expected in children with severe influenza.
There were no new safety signals found in the paediatric population compared to
the adult population.
Clinical laboratory tests, electrocardiograms (ECGs), and vital signs data did
not reveal any pattern of adverse findings associated with IV zanamivir
treatment in paediatric/adolescent patients compared with adult patients. In
this study, children with more severe influenza at the time of enrolment, were
found to have less favourable clinical improvement. The majority of treated
children in this study experienced clinical improvement during the treatment
course. IV zanamivir treatment was associated with an antiviral effect in
paediatric population.
While participants <6 months were not eligible for enrolment in completed GSK
clinical studies of IV zanamivir, patients <6 months of age have been treated
with zanamivir aqueous solution in the compassionate use program (CUP). The CUP
was initiated in 2009 to provide zanamivir aqueous solution (IV or nebulised
administration) on a named patient basis. As of 6 May 2019, the termination
date of the CUP, >4000 requests for zanamivir aqueous solution have been
received, including 406 patients <18 years. Over
96% of patients received zanamivir intravenously. At least 20 patients in the
CUP were 0-6 months (12 born prematurely with a gestation age of 23 -35 weeks).
Study objective
Primary
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.
Secondary
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
Exploratory
To evaluate clinical outcomes following treatment with IV zanamivir
Study design
This will be an open-label, multi-centre and single arm study in neonates and
infants under 6 months of age with complicated influenza infection. Preterm
neonates and infants will be eligible for inclusion but must have reached
Post-Menstrual Age (PMA) of at least 28 weeks.
The total duration of study participation for each participant is up to 24
days, which consists of a study treatment period up to 10 days and 14 days
post-treatment follow up period.
The initial treatment duration is 5 days. However, for a given subject, the
initial 5-day treatment course may be extended for up to 5 additional days if
clinical symptoms, patient characteristics or virological tests as assessed by
the investigator warrant further treatment.
Intervention
The initial dose of IV zanamivir will be determined by PMA/corrected age and
bodyweight. The maintenance dose and interval between the initial dose and
subsequent twice-daily maintenance dose will be further determined by renal
function. Renal function will be monitored if treatment continues beyond 5 days
during the treatment period for dose adjustment if needed.
When the first dose is administered in the morning of Day1, the treatment day
for the twice daily maintenance dosing schedule will correspond to that
calendar day. However if the first dose of IV zanamivir is administered in the
afternoon or evening of Day 1, the twice daily maintenance dosing schedule will
result in one treatment day encompassing two calendar days.
Study burden and risks
The details are based on information from patients ranging from babies above 6
months of age to adult. Some effects cannot be seen in babies but need to be
mentioned to provide as complete a list as is possible.
Serious skin and allergic reactions may occur with zanamivir, but there isn*t
enough information to estimate how likely they are. The doctor will look out
for:
• very severe skin reactions such as a skin rash, which may cause blisters that
may be widespread and include skin peeling.
• severe allergic reactions, including features such as itchy rash, swelling of
the face, throat or tongue, breathing difficulty, light headedness and vomiting.
Common side effects
These may affect up to 1 in 10 people
• diarrhoea
• damage to liver cells (hepatocellular injury). This may show up in blood
tests for your baby as an increase in the level of liver enzymes (raised
aminotransferase).
• rash
Uncommon side effects
These may affect up to 1 in 100 people
• itchy, bumpy rash (hives).
Uncommon side effects that may show up in the blood tests for the baby:
• increase in the level of liver or bone enzymes (raised alkaline phosphatase).
Side effects where it is not known how likely they are to happen
• acting strangely
• seeing, hearing or feeling things which are not there
• confused thinking
• fits (seizures)
• being less alert or not responding to loud sounds or being shaken
Severe flu can cause these symptoms. It is unknown if zanamivir also causes
them. They tend to happen early in the illness and get better quickly. They
have been seen in children with flu who were taking zanamivir and in children
with flu who were not taking zanamivir.
Study procedure:
When taking a blood sample from the baby: they may feel faint, or experience
mild pain, bruising, irritation or redness at the site. In rare cases, they
may get an infection.
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Listed location countries
Age
Inclusion criteria
1. Neonates and infants who are aged less than 6 months (corrected age).
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.
3.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).
4. Body weight >=1kg
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
Current or chronic history of liver disease or known hepatic or biliary
abnormalities.
4. Participants who require concurrent therapy with another influenza antiviral
drug.
5. Participants who have participated in a study using an investigational drug
within 30 days prior to Baseline.
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.
8. Participants who are positive for SARS-CoV-2, as determined by a diagnostic
test, at screening
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-001588-63-NL |
| CCMO | NL75414.091.20 |
| Other | www.gsk-clinicalstudyegister.com; 200925 |