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

Primary Purpose

Influenza, Influenza, Human

Status
Recruiting
Phase
Phase 2
Locations
Thailand
Study Type
Interventional
Intervention
Drug: Oseltamivir
Drug: Favipiravir
Drug: Zanamivir
Drug: Baloxavir
Drug: Molnupiravir
Drug: Peramivir
Drug: Laninamivir
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza focused on measuring Influenza, Phase 2, Antiviral Pharmacodynamics

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept 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 50 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 Haemaglobin <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

Sites / Locations

  • Faculty of Tropical Medicine, Mahidol UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

No Intervention

Arm Label

Oseltamivir (TAMIFLU®)

Favipiravir

Zanamivir (RELENZA®)

Baloxavir (XOFLUZA®)

Molnupiravir

Peramivir (RAPIVAB®)

Laninamivir (INAVIR®)

Negative control group

Arm Description

No treatment (except antipyretics- paracetamol)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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 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

Full Information

First Posted
December 5, 2022
Last Updated
May 9, 2023
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT05648448
Brief Title
A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza
Acronym
AD ASTRA
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 22, 2023 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Influenza, Human
Keywords
Influenza, Phase 2, Antiviral Pharmacodynamics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oseltamivir (TAMIFLU®)
Arm Type
Experimental
Arm Title
Favipiravir
Arm Type
Experimental
Arm Title
Zanamivir (RELENZA®)
Arm Type
Experimental
Arm Title
Baloxavir (XOFLUZA®)
Arm Type
Experimental
Arm Title
Molnupiravir
Arm Type
Experimental
Arm Title
Peramivir (RAPIVAB®)
Arm Type
Experimental
Arm Title
Laninamivir (INAVIR®)
Arm Type
Experimental
Arm Title
Negative control group
Arm Type
No Intervention
Arm Description
No treatment (except antipyretics- paracetamol)
Intervention Type
Drug
Intervention Name(s)
Drug: Oseltamivir
Intervention Description
Oral oseltamivir 75mg BD for 5/7
Intervention Type
Drug
Intervention Name(s)
Drug: Favipiravir
Intervention Description
Oral favipiravir 1800mg BD D0 and 800mg BD for a further 4/7
Intervention Type
Drug
Intervention Name(s)
Drug: Zanamivir
Intervention Description
Inhaled zanamivir 10mg BD for 5/7
Intervention Type
Drug
Intervention Name(s)
Drug: Baloxavir
Intervention Description
Oral baloxavir: <80kg- single dose of 40mg on D0 ≥80kg- single dose of 80mg on D0
Intervention Type
Drug
Intervention Name(s)
Drug: Molnupiravir
Intervention Description
Oral molnupiravir 800mg BD for 5/7
Intervention Type
Drug
Intervention Name(s)
Drug: Peramivir
Intervention Description
Intravenous peramivir 600mg once only
Intervention Type
Drug
Intervention Name(s)
Drug: Laninamivir
Intervention Description
Inhaled laninamivir 40mg once only
Primary Outcome Measure Information:
Title
Rate of viral clearance for currently available drugs and those with potential activity
Description
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 - 7
Secondary Outcome Measure Information:
Title
Rate of viral clearance in early influenza infection
Description
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 - 7
Title
Rate of viral clearance for drugs shown to have considerable antiviral activity
Description
Rate of viral clearance for drugs to determine optimal dosing regimens for drugs shown to have considerable antiviral activity
Time Frame
Days 0 - 7
Title
Time to symptom alleviation and fever duration
Description
Assessment of time to symptom alleviation and fever duration to compare time to symptom resolution and fever duration between interventions
Time Frame
Days 0 - 7
Other Pre-specified Outcome Measures:
Title
Rates of hospitalisation for clinical trial reasons
Description
Rates of hospitalisation for clinical reasons up to day 28
Time Frame
Days 0 - 28
Title
Development of influenza-related complications
Description
Development of influenza-related complications including bronchitis, sinusitis, otitis media and pneumonia requiring antibiotics, up to day 28
Time Frame
Days 0 - 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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 50 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 Haemaglobin <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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William Schilling, MD
Phone
+662 203 6333
Email
william@tropmedres.ac
First Name & Middle Initial & Last Name or Official Title & Degree
Nicholas J White, Prof
Phone
+662 203 6333
Email
nickw@tropmedres.ac
Facility Information:
Facility Name
Faculty of Tropical Medicine, Mahidol University
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weerapong Phumratanaprapin, MD
Email
weerapong.phu@mahidol.ac.th

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
Refer to MORU data sharing policy with other researchers to use in the future. https://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies).
IPD Sharing URL
http://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies

Learn more about this trial

A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza

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