Clinical trial NCT05648448: A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Influenza
Influenza, Human
Keywords: Influenza
Phase 2
Antiviral Pharmacodynamics
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2022-12-13
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Rate of viral clearance for currently available drugs and those with potential activity
timeFrame: Days 0 - 5
Secondary outcomes:
measure: Rate of viral clearance in early influenza infection
timeFrame: Days 0 - 5
measure: Rate of viral clearance for drugs shown to have considerable antiviral activity
timeFrame: Days 0 - 5
measure: Time to symptom alleviation and fever duration
timeFrame: Days 0 - 14
Other outcomes:
measure: Rates of hospitalisation for clinical trial reasons
timeFrame: Days 0 - 28
measure: Development of influenza-related complications
timeFrame: Days 0 - 28
measure: 7. Relationship between viral clearance, randomisation arm and other measures (covariates) and development of symptoms or functional issues following illness with influenza.
timeFrame: Days 0-120
Locations:
city: Minas Gerais
country: Brazil
facility: Universidade Federal de Minas Gerais
city: Vientiane
country: Lao People's Democratic Republic
facility: Laos-Oxford-Mahosot Wellcome Trust Research unit
city: Kathmandu
country: Nepal
facility: Sukraraj Tropical & Infectious Disease Hospital
city: Bangkok
country: Thailand
facility: Faculty of Tropical Medicine, Mahidol University
Study officials:
References: