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A Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of baloxavir marboxil in combination with standard-of-care neuraminidase inhibitor in hospitalized patients with severe influenza

Study to assess efficacy and safety of baloxavir marboxil in combination with standard-of-care neuraminidase inhibitor in hospitalized Patients with severe influenza

366

In the safety population, there were 239 patients in the baloxavir marboxil + SOC NAI group (hereinafter, baloxavir marboxil group) and 124 patients in the placebo + SOC NAI group (hereinafter, placebo group). The age (mean [SD]) was 58.0 (19.8) years in the baloxavir marboxil group and 61.6 (20.3) years in the placebo group. By sex, 51.05% (122/239) were males and 48.95% (117/239) were females in the baloxavir marboxil group, and 54.84% (68/124) were males (68/124) and 45.16% were females (56/124) in the placebo group.

Overall, 366 patients were randomized on a permutated block basis in a 2:1 ratio between the treatment groups with 241 patients in the baloxavir marboxil group and 125 in the placebo group.

The overall incidence of AEs was similar across the 2 treatment groups: 279 AEs in 108 (45.2%) patients in the baloxavir marboxil group compared with 180 AEs in 62 (50.0%) patients in the placebo group. A total of 11 deaths were reported, 4 (1.7%) in the baloxavir marboxil group and 7 (5.6%) in the placebo group. None of the deaths were considered by the investigator to be related to baloxavir marboxil/placebo treatment. The incidence of SAEs was comparable in the two treatment groups; 29 (12.1%) patients experienced a total of 43 SAEs in the baloxavir marboxil group and 19 (15.3%) patients experienced a total of 26 SAEs in the placebo group. The majority of SAEs resolved, and none were considered to be related to treatment in the baloxavir marboxil group. The incidence of AEs leading to withdrawal of study drug was low (1.3% in the baloxavir marboxil group and 3.2% in the placebo group).

The primary efficacy endpoint was not met, since no statistically significant difference in the TTCI was observed between the baloxavir marboxil group (97.5 hrs [95%CI: 75.9, 117.2]) and placebo group (100.2 hrs [95%CI: 75.9, 144.4]) (Wilcoxon p=0.4666).

The results of the key secondary and other secondary efficacy endpoints were consistent with those of the primary endpoint; although the results generally showed numerical improvements in favor of the baloxavir marboxil group, no differences between the two treatment groups were identified in the exploratory statistical tests (p > 0.05 for all analyses). See "adverse events". In the extensive PK population, the geometric mean plasma concentrations of baloxavir 24 hr post-dose were 43.9 and 67.1 ug/mL on Day 1 and Day 4, respectively.

The study did not meet its primary efficacy endpoint. The results of the key secondary and other secondary efficacy endpoints were consistent with those of the primary endpoint; although the results generally showed numerical improvements in favor of the baloxavir marboxil group, no differences between the two treatment groups were identified in the exploratory statistical tests. Baloxavir marboxil was well tolerated, and no new safety signals or adverse drug reactions were identified.

Yes

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Shionogi & Co., Ltd.

shionogiclintrials-admin@shionogi.co.jp

Shionogi & Co., Ltd.

+81-6-6209-7885

shionogiclintrials-admin@shionogi.co.jp

completed

Jan. 08, 2019

Interventional

Multicenter, randomized, double-blind, parallel-group

treatment purpose

3

- Patients who require hospitalization for severe influenza or acquire influenza during hospitalization, the severity of which requires an extension of hospitalization.
- The time interval between the onset of symptoms and randomization is within 96 hours.
etc.

- Known contraindication to neuraminidase inhibitors.
- Patients with known severe renal impairment or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis.
etc.

Both

Influenza A and/or B virus infection

investigational material(s)
Generic name etc : baloxavir marboxil
INN of investigational material : baloxavir marboxil
Therapeutic category code : 625 Anti-virus agents
Dosage and Administration for Investigational material : Oral

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
Time to Clinical Improvement [Time Frame: Up to Day 35]
Time to Clinical Improvement is defined as:
- Time to Hospital Discharge OR
- Time to NEWS2 (National Early Warning Score 2) of 2 or lower maintained for 24 hours

efficacy
pharmacokinetics
safety
- Response Rates of the 6-Point Ordinal Scale at Day 7 [ Time Frame: Day 7 ]
- Percentage of Patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Up to Day 35]
- Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points, etc.

Oct. 24, 2018