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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 6
- 主要终点
- Clearance (CL) in plasma following administration of zanamivir
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
研究组 & 干预措施
Hospitalized neonates and infants with influenza infection
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.
干预措施: Zanamivir (Drug)
结局指标
主要结局
Clearance (CL) in plasma following administration of zanamivir
时间窗: 30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Area under the serum concentration-time curve (AUC) of zanamivir
时间窗: Up to 12 hours after end of infusion on Day 1
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Maximum observed serum concentration (Cmax) of zanamivir
时间窗: Up to 12 hours after end of infusion on Day 1
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Terminal half-life (t1/2) of zanamivir
时间窗: 30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
次要结局
- 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 emergence of resistance to zanamivir(Up to Day 24)
- Number of participants with abnormal findings in body temperature(From start of treatment (Day 1) up to Day 24)
- Viral load over time after administration of zanamivir(Day 1 up to Maximum Day 24)
- Number of participants with phenotypic resistance(Up to Day 24)
- Number of participants with abnormal findings in Oxygen Saturation(From start of treatment (Day 1) up to Day 24)
- Change From Baseline in viral load after administration of zanamivir(Baseline (Day 1) and up to maximum 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 respiration rate(From start of treatment (Day 1) up to Day 24)
- Number of participants with genotypic resistance(Up to Day 24)