A pilot phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalized adults with respiratory syncytial virus infection

• Published in: Clinical microbiology and infection Vol. 29; no. 10; pp. 1320 - 1327
• Main Authors: Nilsson, Anna C., Pullman, John, Napora, Piotr, Luz, Kleber, Gupta, Anil, Draghi, Jorge, Guzman Romero, Ana Karla, Aggarwal, Naresh, Petrova, Galina, Ianus, Juliana, Vijgen, Leen, Scott, Jane, Sinha, Rekha, Rusch, Sarah, Huntjens, Dymphy, Bertzos, Kristi, Stevens, Marita
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2023
• Subjects: Adults; Clinical Medicine; Infectious Medicine; Infektionsmedicin; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Non-hospitalized; Respiratory syncytial virus; RSV; Viral load; Virus; Virus; Adults; Respiratory syncytial virus; RSV; Viral load; Non-hospitalized
• ISSN: 1198-743X; 1469-0691
• DOI: 10.1016/j.cmi.2023.07.004

To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes. RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (−0.837; 1.011), −0.10 (−2.171; 1.963), and −1.03 (−4.746; 2.682) log10 copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log10 copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively. Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. This study is registered with clinicaltrials.gov (NCT03379675).