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
Objectives: To evaluate the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized adults with RSV infection.
Methods: This phase 2a, double-blind, multicenter study randomly assigned RSV-positive adult outpatients, within ≤5 days of symptom onset, in a 1:1:1 ratio to receive either 500 mg rilematovir, 80 mg rilematovir, or placebo once daily for 7 days. The antiviral effect was measured by RSV RNA viral load (VL) using quantitative RT-PCR and Kaplan-Meier (KM) estimates for time to undetectable VL. Clinical outcomes were assessed using KM estimates for the median time to resolution of key RSV symptoms based on patient-reported outcomes.
Results: A total of 72 RSV-positive patients were randomized; 66 had confirmed RSV infection and received either 500 mg rilematovir (n = 23), 80 mg rilematovir (n = 21), or placebo (n = 22). The differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5, and 8 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 the 500 mg rilematovir group, 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 the 80 mg rilematovir group. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90) days for 500 mg, 8.0 (6.86; 12.80) days for 80 mg, and 7.0 (6.62; 10.88) days for placebo. For patients with symptom onset ≤3 days, these times were 5.7 (2.93; 7.01), 8.1 (6.74; 12.80), and 7.9 (6.62; 11.74) days, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43) days for 500 mg rilematovir, 7.6 (5.93; 8.32) days for 80 mg rilematovir, and 9.6 (5.95; 14.00) days for placebo. For patients with symptom onset ≤3 days, these times were 8.0, 7.6, and 11.8 days, respectively.
Discussion: Early administration of rilematovir suggests potential clinical benefits in RSV-infected adults, supporting further development of RSV therapeutic options.