RECRUITINGPhase 2INTERVENTIONAL

Assessing Antiviral Treatments in Early Symptomatic RSV

Assessment of Respiratory SYNcytial Virus antivirALs: A Phase 2 Multi-centre Adaptive Randomised Platform Trial For the Assessment of Antiviral Pharmacodynamics in aCute Symptomatic RSV Infection (ARSYNAL-FC)

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 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

Who May Be Eligible (Plain English)

Who May Qualify: - Patient understands the procedures and requirements and is willing and able to give willing to sign a consent form for full participation in the study - Adults, male or female, aged ≥18 to \<65 years at time of consent - Early symptomatic RSV; at least one reported symptom of RSV (including fever, history of fever, myalgias, headache, cough, fatigue, nasal congestion, rhinorrhoea and sore throat) within 4 days (96 hours) - RSV positive by rapid antigen test OR a positive RT-PCR test for RSV 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 Should NOT Join This Trial: 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 (\<12g/dL for all arms if Ribavirin is in the randomisation) - 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 lactating (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 RSV, 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 influenza or SARS-CoV-2 (i.e. confirmed with positive ATK or RT-PCR) - Received any RSV vaccine within the last year Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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 \<65 years at time of consent * Early symptomatic RSV; at least one reported symptom of RSV (including fever, history of fever, myalgias, headache, cough, fatigue, nasal congestion, rhinorrhoea and sore throat) within 4 days (96 hours) * RSV positive by rapid antigen test OR a positive RT-PCR test for RSV 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 * Haemoglobin \<10g/dL (\<12g/dL for all arms if Ribavirin is in the randomisation) * 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 lactating (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 RSV, 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 influenza or SARS-CoV-2 (i.e. confirmed with positive ATK or RT-PCR) * Received any RSV vaccine within the last year

Treatments Being Tested

DRUG

Ribavirin

Oral ribavirin 400 to 1000mg three times a day for 5 days. Each tablet contains 200mg, The total daily dosage in adults is weight dependent as outlined below; * 40-59.9kg = 1200mg/day * 60-79.9kg = 1800mg/day * 80-99.9kg = 2400mg/day * ≥100kg = 3000mg/day

DRUG

Molnupiravir

Oral molnupiravir 800mg BD for 5 days

DRUG

Favipiravir

Oral favipiravir 1800mg BD on Day 0, and 800mg BD for a further 4 days

Locations (2)

Laos-Oxford-Mahosot Hospital-Wellcome Trust Research Unit

Vientiane, Laos

Faculty of Tropical Medicine, Mahidol University

Bangkok, Thailand