Assessing Antiviral Treatments in Early Symptomatic RSV

Официальное название

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)

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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
• Препарат Molnupiravir
  Oral molnupiravir 800mg BD for 5 days
• Препарат Favipiravir
  Oral favipiravir 1800mg BD on Day 0, and 800mg BD for a further 4 days

Первичные конечные точки

• Rate of viral clearance for interventions relative to no study drug arm (superiority comparison) [Срок оценки: Days 0-5]

Вторичные конечные точки (5)

• Rate of RSV clearance in early infection [Срок оценки: Days 0-5]
• Rate of RSV clearance for drugs with evidence of antiviral activity [Срок оценки: Days 0-5]
• Assessment of time to symptom alleviation across interventions [Срок оценки: Days 0-14]
• Assessment of fever duration across interventions [Срок оценки: Days 0-14]
• Effects of drugs on the development of drug resistant viral mutants [Срок оценки: Days 0-14]

Критерии участия

Критерии включения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Laos · 1 центр

• Laos-Oxford-Mahosot Hospital-Wellcome Trust Research Unit — Vientiane

Таиланд · 1 центр

• Faculty of Tropical Medicine, Mahidol University — Bangkok

Идентификаторы

NCT: NCT06488300 · VIR24001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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