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
(2023) In Clinical Microbiology and Infection 29(10). p.1320-1327- Abstract
Objectives: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. Methods: 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. Results: RSV-positive patients (n = 72) were randomly... (More)
Objectives: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. Methods: 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. Results: 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. Discussion: Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. Trial registration: This study is registered with clinicaltrials.gov (NCT03379675).
(Less)
- author
- author collaboration
- organization
- publishing date
- 2023-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adults, Non-hospitalized, Respiratory syncytial virus, RSV, Viral load, Virus
- in
- Clinical Microbiology and Infection
- volume
- 29
- issue
- 10
- pages
- 8 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:37422079
- scopus:85167426359
- ISSN
- 1198-743X
- DOI
- 10.1016/j.cmi.2023.07.004
- language
- English
- LU publication?
- yes
- id
- aac71717-7b4c-456f-b864-c134cba2f06f
- date added to LUP
- 2023-11-16 15:21:04
- date last changed
- 2024-04-28 06:54:01
@article{aac71717-7b4c-456f-b864-c134cba2f06f,
abstract = {{<p>Objectives: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. Methods: 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. Results: 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) log<sub>10</sub> 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) log<sub>10</sub> 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. Discussion: Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. Trial registration: This study is registered with clinicaltrials.gov (NCT03379675).</p>}},
author = {{Nilsson, Anna C. and Pullman, John and Napora, Piotr and Luz, Kleber and Gupta, Anil and Draghi, Jorge and Guzman Romero, Ana Karla and Aggarwal, Naresh and Petrova, Galina and Ianus, Juliana and Vijgen, Leen and Scott, Jane and Sinha, Rekha and Rusch, Sarah and Huntjens, Dymphy and Bertzos, Kristi and Stevens, Marita}},
issn = {{1198-743X}},
keywords = {{Adults; Non-hospitalized; Respiratory syncytial virus; RSV; Viral load; Virus}},
language = {{eng}},
number = {{10}},
pages = {{1320--1327}},
publisher = {{Wiley-Blackwell}},
series = {{Clinical Microbiology and Infection}},
title = {{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}},
url = {{http://dx.doi.org/10.1016/j.cmi.2023.07.004}},
doi = {{10.1016/j.cmi.2023.07.004}},
volume = {{29}},
year = {{2023}},
}