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Randomized Controlled Trial
. 2021 Apr 30;10(4):477-484.
doi: 10.1093/jpids/piaa145.

Baloxavir Treatment in Adolescents With Acute Influenza: Subgroup Analysis From the CAPSTONE-1 Trial

Simon Portsmouth  1 , Frederick G Hayden  2 , Keiko Kawaguchi  3 , Toru Ishibashi  3 , Masahiro Kinoshita  3 , Takao Shishido  4 , Kenji Tsuchiya  3 , Takeki Uehara  3
Affiliations
Randomized Controlled Trial

Baloxavir Treatment in Adolescents With Acute Influenza: Subgroup Analysis From the CAPSTONE-1 Trial

Simon Portsmouth et al. J Pediatric Infect Dis Soc. .

Abstract

Background: Baloxavir marboxil has demonstrated safety and efficacy in treating adult and adolescent outpatients with acute influenza (CAPSTONE-1 trial). Here, we report a subgroup analysis of outcomes in adolescents from the trial.

Methods: CAPSTONE-1 was a randomized, double-blind, placebo-controlled study. Eligible adolescent outpatients (aged 12-17 years of age) were randomized in a ratio of 2:1 to a single dose of baloxavir 40/80 mg if less than/greater than or equal to 80 kg or placebo. The main outcomes were the time to alleviation of symptoms (TTAS), duration of infectious virus detection, and incidence of adverse events (AEs).

Results: Among 117 adolescent patients, 90 (77%) comprised the intent-to-treat infected population (63 baloxavir and 27 placebo; 88.9% A(H3N2)). The median TTAS was 38.6 hours shorter (95% confidence interval: -2.6, 68.4) in the baloxavir group compared with placebo (median TTAS, 54.1 hours vs 92.7 hours, P = .0055). The median time to sustained cessation of infectious virus detection was 72.0 hours for baloxavir compared with 120.0 hours for placebo recipients (P < .0001). Treatment-emergent PA/I38X-substituted viruses were detected in 5 of the 51 (9.8%) baloxavir recipients. In the safety population (76 baloxavir and 41 placebo), AEs were less common in baloxavir than placebo recipients (17.1% vs 34.1%; P = .0421). In the baloxavir group, no AEs except for diarrhea were reported in 2 or more patients.

Conclusions: Baloxavir demonstrated clinical and virologic efficacy in the otherwise healthy adolescents with acute influenza compared with placebo. There were no safety concerns identified. These results were similar to the adult population in CAPSTONE-1 and support baloxavir as a treatment option in adolescents.

Keywords: adolescent; baloxavir; cap-dependent endonuclease; influenza.

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Figures

Figure 1.
Figure 1.
Patient disposition. When dual enrollment is occurred, the patient was counted only once. Abbreviation: ITTI, intent-to-treat infected.
Figure 2.
Figure 2.
Time to alleviation of symptoms (TTAS) (A) and time to resolution of fever (B) in the adolescent subpopulation of ITTI population. TTAS was defined as the time between the initiation of the study treatment and the time when the patient’s self-assessed 7 influenza-related symptoms become absent or mild for at least 21.5 hours. Time to resolution of fever was defined as the time between the initiation of the study treatment and the time when the patient’s self-measured axillary temperature becomes less than 37°C for at least 12 hours. Abbreviation: ITTI, intent-to-treat infected.
Figure 3.
Figure 3.
Observed infectious virus titer (A) and observed infectious viral RNA titers (B) (mean ± SD) in the adolescent subpopulation of ITTI population. Patients with positive for influenza virus titer at baseline were included in this analysis. Abbreviations: ITTI, intent-to-treat infected; TCID50, 50% tissue culture infectious dose; SD, standard deviation.
Figure 4.
Figure 4.
Comparison of pharmacokinetic parameters in adolescents (12-17) and adults (18-64) patients in CAPSTONE-1 study.
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