Clinical trial NCT06488300: Assessing Antiviral Treatments in Early Symptomatic RSV
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Respiratory Syncytial Virus
Respiratory Syncytial Virus, Human
Keywords: Respiratory Syncytial Virus
Phase 2
Antiviral Pharmacodynamics
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2024-07-05
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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

Detailed description: There are no proven effective drug treatments for RSV. While vaccines are becoming available, and monoclonal antibodies exist for prevention in infants, antiviral treatments are still urgently needed.

The study is a randomised, open label, controlled, adaptive platform trial that will be conducted in low-risk adult patients (18 - \<65 years old) with early symptomatic RSV, recruited from outpatient acute respiratory infection clinics (ARIs), other approved facilities, or by patient self-referral to the study site. The primary pharmacodynamic measure in this study is the rate of viral clearance following treatment. Individual patient's involvement for this study is 28 days.

This platform will compare antivirals with potential RSV antiviral activity, against a negative control (no treatment). Currently, interventions included in the platform are;

* Interventions licensed for paediatric RSV infections: ribavirin.
* Interventions with antiviral activity against RSV demonstrated in in-vitro studies: molnupiravir and favipiravir

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.

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 \<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

Primary outcomes:
measure: Rate of viral clearance for interventions relative to no study drug arm (superiority comparison)
timeFrame: Days 0-5
Secondary outcomes:
measure: Rate of RSV clearance in early infection
timeFrame: Days 0-5
measure: Rate of RSV clearance for drugs with evidence of antiviral activity
timeFrame: Days 0-5
measure: Assessment of time to symptom alleviation across interventions
timeFrame: Days 0-14
measure: Assessment of fever duration across interventions
timeFrame: Days 0-14
measure: Effects of drugs on the development of drug resistant viral mutants
timeFrame: Days 0-14
Other outcomes:
measure: Hospitalisation for clinical reasons
timeFrame: Days 0-28
measure: Number of participants with virus-related complications
timeFrame: Days 0-28
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Tropical Medicine, Mahidol University
Study officials:
References: