InfluenzaPhase 2AD ASTRANCT05648448
A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza
A Phase 2 study testing Oseltamivir, Favipiravir and Zanamivir in people with Influenza and Influenza, Human, run by University of Oxford at 4 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Influenza, Influenza, Human
- What is being tested?
- Oseltamivir, Favipiravir and Zanamivir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,000 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 22 Feb 2023to 1 Jan 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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 locations and contacts
4 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 4 countries
Brazil1 site, 1 recruiting
- Recruiting
Universidade Federal de Minas Gerais
Minas Gerais
Mauro Martins Teixeira, mmtex.ufmg@gmail.com
Laos1 site, 1 recruiting
- Recruiting
Laos-Oxford-Mahosot Wellcome Trust Research unit
Vientiane
Elizabeth Ashley, Professor, liz@tropmedres.ac
Nepal1 site, 1 recruiting
- Recruiting
Sukraraj Tropical & Infectious Disease Hospital
Kathmandu
Abhilasha Karkey, Dr, akarkey@oucru.org
Thailand1 site, 1 recruiting
- Recruiting
Faculty of Tropical Medicine, Mahidol University
Bangkok, 10400
Weerapong Phumratanaprapin, MD, weerapong.phu@mahidol.ac.th
About this study
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)
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
Read the 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.
- Conditions
- Influenza, Influenza, Human
- Being tested
- Oseltamivir, Favipiravir, Zanamivir, Baloxavir, Molnupiravir
- Keywords
- Influenza, Phase 2, Antiviral Pharmacodynamics
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OseltamivirDrug
Oral oseltamivir 75mg BD for 5/7
FavipiravirDrug
Oral favipiravir 1800mg BD D0 and 800mg BD for a further 4/7
ZanamivirDrug
Inhaled zanamivir 10mg BD for 5/7
BaloxavirDrug
Oral baloxavir:
- <80kg- single dose of 40mg on D0
- ≥80kg- single dose of 80mg on D0
MolnupiravirDrug
Oral molnupiravir 800mg BD for 5/7
PeramivirDrug
Intravenous peramivir 600mg once only
LaninamivirDrug
Inhaled laninamivir 40mg once only
Oseltamivir and BaloxavirDrug
Oseltamivir 75mg BD for 5/7 and
Baloxavir:
- <80kg- single dose of 40mg on D0
- ≥80kg- single dose of 80mg on D0
Oseltamivir and FavipiravirDrug
Oseltamivir 75mg BD for 5/7 and
favipiravir 1800mg BD D0 and 800mg BD for a further 4/7
Favipiravir and BaloxavirDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Oseltamivir (TAMIFLU®) | Experimental | Not described Receives: Drug: Oseltamivir |
| Favipiravir | Experimental | Not described Receives: Drug: Favipiravir |
| Zanamivir (RELENZA®) [Pending addition] | Experimental | Not described Receives: Drug: Zanamivir |
| Baloxavir (XOFLUZA®) | Experimental | Not described Receives: Drug: Baloxavir |
| Molnupiravir [Pending addition] | Experimental | Not described Receives: Drug: Molnupiravir |
| Peramivir (RAPIVAB®) [Pending addition] | Experimental | Not described Receives: Drug: Peramivir |
| Laninamivir (INAVIR®) [Pending addition] | Experimental | Not described Receives: Drug: Laninamivir |
| Oseltamivir and Baloxavir [Pending addition] | Experimental | Not described Receives: Drug: Oseltamivir and Baloxavir |
| Oseltamivir and Favipiravir [Pending addition] | Experimental | Not described Receives: Drug: Oseltamivir and Favipiravir |
| Favipiravir and Baloxavir [Pending addition] | Experimental | Not described Receives: Drug: Favipiravir and Baloxavir |
| Negative control group | No intervention | No treatment (except antipyretics- paracetamol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Days 0 - 5
Secondary outcomes (3)
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
Measured: Days 0 - 5
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
Measured: Days 0 - 5
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
Measured: Days 0 - 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2022
- Study start22 Feb 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05648448
- Sponsor's protocol ID
- VIR22003
- Acronym
- AD ASTRA
- Status last verified
- Feb 2026
- First submitted
- 5 Dec 2022
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: With patient's consent, clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future. https://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies). The data generated in this study belongs to the study group as a whole. The final database will be shared amongst the site PI and key members of the research team. The database may be shared with researchers not directly involved in this study after the main paper has been published and in accordance with MORU guidelines on data sharing.
Publications
Jittamala P, Schilling WHK, Leopold SJ, Watson JA, Kotchum K, Wongnak P, Seers T, Asawasriworanan T, Singh S, Beer E, Ngernseng T, Suwannasin K, Madmanee W, Phommasone K, Shrestha S, de Aguiar RS, Batty EM, Teixeira MM, Karkey A, Ashley EA, Intalapaporn P, Luvira V, Phumratanaprapin W, Chotivanich K, Imwong M, White NJ; AD ASTRA Collaborative Group. Baloxavir marboxil, favipiravir, or oseltamivir in patients with non-severe symptomatic seasonal influenza (AD ASTRA): a phase 2, open-label, adaptive, randomised controlled trial. Lancet Infect Dis. 2026 Jul 28:S1473-3099(26)00255-0. doi: 10.1016/S1473-3099(26)00255-0. Online ahead of print.
PubMed 42520824