ADaptive ASsessment of TReatments for influenzA: A Phase 2 Multi-centre Adaptive Randomised Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic Influenza Infection (AD ASTRA)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 3,000
- 试验地点
- 7
- 主要终点
- Rate of viral clearance for currently available drugs and those with potential activity
研究概览
简要总结
This trial will use a previously validated platform, to quantitatively assess antiviral effects in low-risk patients with high viral burdens and uncomplicated influenza, to determine in-vivo antiviral activity. In this randomised, open-label, controlled, group sequential, adaptive, platform trial, we will compare the performance of available influenza antivirals, and those with potential activity, relative to the control (no treatment) and each other.
AD ASTRA study is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator
详细描述
Several influenza antivirals are licensed, differing in availability and routes of administration. Direct comparisons of antiviral and clinical efficacy between the multiple available antivirals are lacking. This comparative information is important for guideline development and for aiding purchasing and prioritisation decisions with several options available.
The platform trial will assess the following interventions:
- Licensed influenza antiviral interventions: oseltamivir (TAMIFLU®), peramivir (RAPIVAB®), zanamivir (RELENZA®), laninamivir (INAVIR®), baloxavir (XOFLUZA®) and favipiravir alone and in combination. The interventions will be chosen in order of priority as well as local feasibility at sites (availability of drugs, local ethics committee and regulatory approvals)
- Interventions with antiviral activity against influenza demonstrated in pre-clinical studies: molnupiravir
Randomisation to the no antiviral treatment control arm (no intervention) will be fixed at a minimum of 20% throughout the study. The randomisation ratios will be uniform for all available interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient understands the procedures and requirements and is willing and able to give informed consent for full participation in the study
- •Adults, male or female, aged 18 to 60 years at time of consent.
- •Early symptomatic Influenza (A or B); at least one reported symptom of influenza (including fever, history of fever, myalgias, headache, cough, fatigue, nasal congestion, rhinorrhoea and sore throat) within 4 days (96 hours)
- •Influenza positive by rapid antigen test OR a positive RT-PCR test for influenza viruses within the last 24hrs with a Ct value of <30
- •Able to walk unaided and unimpeded in activities of daily living (ADLs)
- •Agrees and is able to adhere to all study procedures, including availability and contact information for follow-up visits
排除标准
- •The patient may not enter the study if ANY of the following apply:
- •Taking any concomitant medications or drugs which could interact with the study medications or have antiviral activity
- •Presence of any chronic illness/condition requiring long term treatment or other significant comorbidity
- •BMI ≥35 Kg/m2
- •Clinically relevant laboratory abnormalities discovered at screening
- •Haemoglobin <10g/dL
- •Platelet count <100,000/uL
- •ALT > 2x ULN
- •Total bilirubin >1.5 x ULN
- •eGFR <70mls/min/1.73m2
- •For females: pregnancy, actively trying to become pregnant or lactation (healthy women on OCP are eligible to join)
- •Contraindication to taking, or known hypersensitivity reaction to any of the proposed therapeutics
- •Currently participating in another interventional influenza or COVID-19 therapeutic trial
- •Clinical evidence of pneumonia- e.g. shortness of breath, hypoxaemia, crepitations (imaging not required)
- •Known to be currently co-infected with SARS-CoV-2 (i.e. confirmed with positive ATK or RT-PCR)
- •Received live attenuated influenza virus vaccine within 3 weeks prior to study entry
研究组 & 干预措施
Negative control group
No treatment (except antipyretics- paracetamol)
Oseltamivir and Favipiravir [Pending addition]
干预措施: Oseltamivir and Favipiravir (Drug)
Oseltamivir and Baloxavir [Pending addition]
干预措施: Oseltamivir and Baloxavir (Drug)
Molnupiravir [Pending addition]
干预措施: Molnupiravir (Drug)
Favipiravir and Baloxavir [Pending addition]
干预措施: Favipiravir and Baloxavir (Drug)
Oseltamivir (TAMIFLU®)
干预措施: Oseltamivir (Drug)
Favipiravir
干预措施: Favipiravir (Drug)
Zanamivir (RELENZA®) [Pending addition]
干预措施: Zanamivir (Drug)
Baloxavir (XOFLUZA®)
干预措施: Baloxavir (Drug)
Peramivir (RAPIVAB®) [Pending addition]
干预措施: Peramivir (Drug)
Laninamivir (INAVIR®) [Pending addition]
干预措施: Laninamivir (Drug)
结局指标
主要结局
Rate of viral clearance for currently available drugs and those with potential activity
时间窗: Days 0 - 5
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/saliva taken daily from baseline (day 0) to day 7 for each therapeutic arm compared with the no antiviral treatment control i.e. those not receiving study drug
次要结局
- Rate of viral clearance for drugs shown to have considerable antiviral activity(Days 0 - 5)
- Rate of viral clearance in early influenza infection(Days 0 - 5)
- Time to symptom alleviation and fever duration(Days 0 - 14)