Assessing Antiviral Treatments in Early Symptomatic RSV
NCT Number: NCT06488300
Acronym: ARSYNAL-FC
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Respiratory Syncytial Virus|Respiratory Syncytial Virus, Human
Interventions: DRUG: Ribavirin|DRUG: Molnupiravir|DRUG: Favipiravir
Sponsor: University of Oxford
Sex: ALL
Age: ADULT
Enrollment: 1000
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-01
Completion Date: 2027-01-01
Locations: Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand

Summary:
This trial will use a previously validated platform, to quantitatively assess antiviral effects in low-risk patients with high viral burdens and uncomplicated Respiratory Syncytial Virus (RSV), to determine in-vivo antiviral activity. In this randomised, open-label, controlled, group sequential adaptive platform trial, we will assess and compare the performance of currently licensed interventions (including repurposed drugs) with activity against RSV, and those with potential activity demonstrated in pre-clinical and early clinical studies relative to each-other, and the control (no antiviral treatment).

ARSYNAL-FC study is funded by Wellcome Trust Grant ref: 226933/Z/23/Z through the COVID-19 Therapeutics Accelerator

Primary Outcome Measures: Rate of viral clearance for interventions relative to no study drug arm (superiority comparison), 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 5 for each therapeutic arm compared with the contemporaneous no antiviral treatment control/ positive control, Days 0-5
Secondary Outcome Measures: Rate of RSV clearance in early infection, Rate of viral clearance in early RSV infection to characterise the determinants of RSV clearance in early infection e.g., contribution of baseline serology, virus type/subtype, prior vaccination, host genetics, Days 0-5|Rate of RSV clearance for drugs with evidence of antiviral activity, Rate of viral clearance to determine optimal dosing regimens for drugs with evidence of antiviral activity, Days 0-5|Assessment of time to symptom alleviation across interventions, Time to symptom resolution across interventions, Days 0-14|Assessment of fever duration across interventions, Area under the curve of recorded temperature across interventions, Days 0-14|Effects of drugs on the development of drug resistant viral mutants, To determine the effects of drugs on the development of drug resistant viral mutants between intervention and no treatment arm, measuring the number of mutations known to confer resistance in detectable virus at later time points, Days 0-14
Other Outcome Measures: Hospitalisation for clinical reasons, To characterise the relationship between viral clearance and hospitalisation for clinical reasons up to day 28, Days 0-28|Number of participants with virus-related complications, Number of participants with virus-related complications including bronchitis, sinusitis, otitis media and pneumonia requiring antibiotics, up to day 28, where the diagnosis is made and documented by the study clinician., Days 0-28