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A7715 - Safety and Efficacy of Oral RV521 in a Human Respiratory Syncytial Virus (RSV) Phase 2a Challenge Study
Author Block: J. DeVincenzo1, D. Tait2, O. Oluwayi3, J. Mori3, E. Thomas2, N. Mathews2, R. Harland2, S. Cockerill2, K. Powell2, E. Littler2; 1Department of Pediatrics, University of Tennessee, Memphis, TN, United States, 2ReViral Ltd, Stevenage, United Kingdom, 3hVivo, London, United Kingdom.
RATIONALE: RSV is a major cause of lower respiratory tract infections manifesting as bronchiolitis or pneumonia in infants, children, and elderly and immunocompromised adults. No effective antiviral treatment currently exists. RV521 is an oral small molecule RSV fusion inhibitor in development for the treatment of RSV infection in infants and adults. METHODS: In a randomized, double-blind, phase 2a clinical trial in healthy adult volunteers inoculated with the RSV-A isolate Memphis-37, participants received RV521 or placebo (2:1), twice daily for 5 days, either 12 hours after confirmation of active RSV infection or on the fifth day after inoculation if RSV was not detected. Viral load, disease severity, pharmacokinetics and safety were measured throughout the 12-day study quarantine period. The primary efficacy end point was the area under the curve (AUC) of RSV viral load determined by RT-qPCR from nasal wash samples collected immediately prior to administration of the first dose of RV521 and twice-daily through the 12th day following inoculation in subjects with confirmed RSV infection. Secondary efficacy end points included viral load as determined by quantitative culture, symptom scores, and weight of nasal mucus produced. RESULTS: A total of 66 participants were inoculated with RSV and randomised to receive RV521 (at doses of 200mg or 350mg orally twice daily, with no loading dose) or placebo (2:1). 53 participants (80%) were confirmed to be infected with RSV by RT-qPCR. The AUCs for RT-qPCR viral load were significantly lower for 350mg RV521 (n=16) and 200mg RV521 (n=18) compared to placebo (n=19) with reductions in group mean Log10 RT-qPCR viral AUCs of 63% and 55% respectively. The AUC for viral load by quantitative culture, AUC of total symptom score, and the total mucus weight produced were also significantly reduced in participants receiving RV521 compared with the placebo group. Safety analysis demonstrated no changes in laboratory determined safety parameters, and a balanced adverse event profile between and within both dose groups and placebo. No treatment related serious adverse events occurred. CONCLUSIONS: Therapeutic administration of RV521, an oral RSV fusion inhibitor, safely and effectively reduces viral load and disease severity in a phase 2a challenge model and should be further evaluated in RSV-infected adults and children.