A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza (AD ASTRA)

University of Oxford

Status and phase: Enrolling; Phase 2

Conditions: Influenza, Human; Influenza

Treatments: Drug: Oseltamivir and Favipiravir; Drug: Favipiravir and Baloxavir; Drug: Zanamivir; Drug: Oseltamivir and Baloxavir; Drug: Baloxavir; Drug: Favipiravir; Drug: Peramivir; Drug: Laninamivir; Drug: Oseltamivir; Drug: Molnupiravir

Study type: Interventional

Funder types: Other

Identifiers

NCT05648448

VIR22003

Details and patient eligibility

About

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

Full 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.

Enrollment: 3,000 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,000 participants in 11 patient groups

Oseltamivir (TAMIFLU®)

Experimental group

Treatment:

Drug: Oseltamivir

Favipiravir

Experimental group

Treatment:

Drug: Favipiravir

Zanamivir (RELENZA®) [Pending addition]

Experimental group

Treatment:

Drug: Zanamivir

Baloxavir (XOFLUZA®)

Experimental group

Treatment:

Drug: Baloxavir

Molnupiravir [Pending addition]

Experimental group

Treatment:

Drug: Molnupiravir

Peramivir (RAPIVAB®) [Pending addition]

Experimental group

Treatment:

Drug: Peramivir

Laninamivir (INAVIR®) [Pending addition]

Experimental group

Treatment:

Drug: Laninamivir

Oseltamivir and Baloxavir [Pending addition]

Experimental group

Treatment:

Drug: Oseltamivir and Baloxavir

Oseltamivir and Favipiravir [Pending addition]

Experimental group

Treatment:

Drug: Oseltamivir and Favipiravir

Favipiravir and Baloxavir [Pending addition]

Experimental group

Treatment:

Drug: Favipiravir and Baloxavir

Negative control group

No Intervention group

Description:

No treatment (except antipyretics- paracetamol)