Health Trials

A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza

ConditionsInfluenzaInfluenza, Human
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-60
SponsorUniversity of Oxford

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Oseltamivir

    Drug

    Oral oseltamivir 75mg BD for 5/7

  • Favipiravir

    Drug

    Oral favipiravir 1800mg BD D0 and 800mg BD for a further 4/7

  • Zanamivir

    Drug

    Inhaled zanamivir 10mg BD for 5/7

  • Baloxavir

    Drug

    Oral baloxavir: * \<80kg- single dose of 40mg on D0 * ≥80kg- single dose of 80mg on D0

  • Molnupiravir

    Drug

    Oral molnupiravir 800mg BD for 5/7

  • Peramivir

    Drug

    Intravenous peramivir 600mg once only

  • Laninamivir

    Drug

    Inhaled laninamivir 40mg once only

  • Oseltamivir and Baloxavir

    Drug

    Oseltamivir 75mg BD for 5/7 and Baloxavir: * \<80kg- single dose of 40mg on D0 * ≥80kg- single dose of 80mg on D0

  • Oseltamivir and Favipiravir

    Drug

    Oseltamivir 75mg BD for 5/7 and favipiravir 1800mg BD D0 and 800mg BD for a further 4/7

  • Favipiravir and Baloxavir

    Drug

    favipiravir 1800mg BD D0 and 800mg BD for a further 4/7 Baloxavir: * \<80kg- single dose of 40mg on D0 * ≥80kg- single dose of 80mg on D0

Treatment groups

3,000 Participants
are divided into 11 treatment groups

11

Treatment groups

See each treatment group below.

Group A: Oseltamivir (TAMIFLU®)Experimental treatment 1 intervention
Group B: FavipiravirExperimental treatment 1 intervention
Group C: Zanamivir (RELENZA®) [Pending addition]Experimental treatment 1 intervention
Group D: Baloxavir (XOFLUZA®)Experimental treatment 1 intervention
Group E: Molnupiravir [Pending addition]Experimental treatment 1 intervention
Group F: Peramivir (RAPIVAB®) [Pending addition]Experimental treatment 1 intervention
Group G: Laninamivir (INAVIR®) [Pending addition]Experimental treatment 1 intervention
Group H: Oseltamivir and Baloxavir [Pending addition]Experimental treatment 1 intervention
Group I: Oseltamivir and Favipiravir [Pending addition]Experimental treatment 1 intervention
Group J: Favipiravir and Baloxavir [Pending addition]Experimental treatment 1 intervention
Group K: Negative control groupNo intervention 0 interventions

Trial outcomes

Primary outcomes

1

Rate of viral clearance for currently available drugs and those with potential activity

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

Time frame
Days 0 - 5

Secondary outcomes

1

Rate of viral clearance in early influenza infection

Rate of viral clearance in early influenza infection to characterise the determinants of viral clearance in early influenza infection e.g. contribution of baseline serology, influenza type/subtype, prior vaccination

Time frame
Days 0 - 5
2

Rate of viral clearance for drugs shown to have considerable antiviral activity

Rate of viral clearance for drugs to determine optimal dosing regimens for drugs shown to have considerable antiviral activity

Time frame
Days 0 - 5
3

Time to symptom alleviation and fever duration

Assessment of time to symptom alleviation and fever duration to compare time to symptom resolution and fever duration between interventions

Time frame
Days 0 - 14

Other outcomes

1

Rates of hospitalisation for clinical trial reasons

Rates of hospitalisation for clinical reasons up to day 28

Time frame
Days 0 - 28
2

Development of influenza-related complications

Development of influenza-related complications including bronchitis, sinusitis, otitis media and pneumonia requiring antibiotics, up to day 28

Time frame
Days 0 - 28
3

7. Relationship between viral clearance, randomisation arm and other measures (covariates) and development of symptoms or functional issues following illness with influenza.

This will be scored using the Modified Influenza Yorkshire Rehabilitation Scale (Flu-YRSm), adapted from the Modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm).

Time frame
Days 0-120

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Oxford

Lead sponsor

Source ClinicalTrials.gov
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