CAPSTONE-1

A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza (CAPSTONE 1) https://clinicaltrials.gov/ct2/show/NCT02954354

Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379:913-923 https://www.nejm.org/doi/full/10.1056/NEJMoa1716197

Clinical Question

For the treatment of influenza in adults and adolescents, is baloxavir superior to placebo and non-inferior to oseltamivir?

Bottom Line

Baloxavir is superior to placebo in reduction of both viral load and symptoms of influenza. Baloxavir provides influenza symptom resolution that is comparable to oseltamivir.

Major Points

CAPSTONE-1 compared baloxavir to both placebo and oseltamivir in patients 12-64 years of age with influenza-like illness in the United States and Japan from November 2016 to March 2017. Time to symptom alleviation was 26.5 hours shorter with baloxavir versus placebo overall, however symptom alleviation seemed to occur much earlier in adolescents (ages 12-19). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir.

Results from the phase 3 CAPSTONE-1 trial (along with another phase 2 trial used for dose ranging) were used in the NDA submitted to the FDA. Baloxavir marboxil was granted priority review by the FDA in order take action on the application within an expedited time frame, due to the small number of therapeutic options for treatment of influenza. On October 24th, 2018, FDA approved baloxavir marboxil under the trade name Xofluza™ for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours.

Design

• Multicenter, double-blind, placebo and oseltamivir controlled, randomized trial
• N=1,064
  • Baloxavir Group: 456
  • Placebo Group: 231
  • Oseltamivir Group: 377
• Setting: Outpatient treatment in the United States and Japan
• Enrollment: November 2016 to March 2017
• Analysis: Intention-to-treat

Population

Inclusion Criteria

• Age 12-64 years

Exclusion Criteria

• Disease requiring hospitalization
• Influenza diagnosis not confirmed

Baseline Characteristics

• Median age
  • Baloxavir Group: 32
  • Placebo Group: 33
  • Oseltamivir Group: 35
• Male sex (%)
  • Baloxavir Group: 50.9
  • Placebo Group: 51.9
  • Oseltamivir Group: 57.8

Interventions

• Enrolled patients were randomized to baloxavir, placebo, or oseltamivir treatment groups
• Patients aged 12 to 19 years were randomly assigned, in a 2:1 ratio, to receive either baloxavir or placebo on day 1 only.
• Patients aged 20 to 64 years were randomly assigned, in a 2:2:1 ratio, to receive a single oral weight based dose of baloxavir, oseltamivir at a dose of 75 mg twice daily for 5 days, or matching placebos. Patients in all three groups received a 5-day regimen (baloxavir and a placebo, oseltamivir and a placebo, or placebos only).
• For all patients, the first dose of the trial regimen was administered under observation.

Outcomes

Comparisons are baloxavir vs. placebo

Primary Outcomes

Median time to alleviation of influenza symptoms

53.7 hours in the baloxavir group vs. 80.2 hours in the placebo group, P<0.001