RecruitingPhase 2NCT05648448

A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza

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)


Sponsor

University of Oxford

Enrollment

3,000 participants

Start Date

Feb 22, 2023

Study Type

INTERVENTIONAL

Conditions

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


Eligibility

Min Age: 18 YearsMax Age: 60 Years

Inclusion Criteria6

  • 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 Criteria16

  • 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

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Interventions

DRUGOseltamivir

Oral oseltamivir 75mg BD for 5/7

DRUGFavipiravir

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

DRUGZanamivir

Inhaled zanamivir 10mg BD for 5/7

DRUGBaloxavir

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

DRUGMolnupiravir

Oral molnupiravir 800mg BD for 5/7

DRUGPeramivir

Intravenous peramivir 600mg once only

DRUGLaninamivir

Inhaled laninamivir 40mg once only

DRUGOseltamivir and Baloxavir

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

DRUGOseltamivir and Favipiravir

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

DRUGFavipiravir and Baloxavir

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


Locations(4)

Universidade Federal de Minas Gerais

Minas Gerais, Brazil

Laos-Oxford-Mahosot Wellcome Trust Research unit

Vientiane, Laos

Sukraraj Tropical & Infectious Disease Hospital

Kathmandu, Nepal

Faculty of Tropical Medicine, Mahidol University

Bangkok, Thailand

View Full Details on ClinicalTrials.gov

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NCT05648448


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