Treatment of baloxavir marboxil in immunocompromised patients with influenza infection

Lead Investigator: Bin Cao, China-Japan Friendship Hospital
Title of Proposal Research: Treatment of baloxavir marboxil in immunocompromised patients with influenza infection
Vivli Data Request: 8896
Funding Source: None
Potential Conflicts of Interest: In the transmission study initiated by Roche as the China leading PI. However, the request for the analysis of the current data is based solely on clinical needs and has no interest in Roche.
To mitigate any conflicts of interest, I will declare them in any subsequent publication and ensure that all data and results are accurate and unbiased. I will also disclose any financial or personal relationships that may have influenced my research and take steps to minimize any potential bias. Additionally, I will work closely with my team to ensure that all research is conducted with the highest ethical standards and that any potential conflicts of interest are addressed appropriately.

Summary of the Proposed Research:

Influenza virus infection is one of the most common infectious diseases around the world, with about 3-5 million people suffer from severe influenza and about 290000-650000 death each year. Immunocompromised patients and patients with structural lung disease with influenza infections suffered from even worse clinical prognosis compared with immunocompetent popuation, with one study showing that 73% hospitalization in intensive care unit and 7% mortality among immunosuppressed patients treated with antiviral drugs. Therefore, new antivirals are urgently needed to improve outcomes for these patients.

There is limited data about neuraminidase inhibitors (NAIs) vs Baloxavir or NAIs+Baloxavir vs NAIs in immunocompromised patients with influenza infections. NAIs such as Oseltamivir are first-line treatment options for influenza, these drugs work by blocking the release of the newly created viruses from cells. Baloxavir is a novel antiviral drug used to treat influenza, which can stop the virus from replicating in cells. Clinical trials have shown that Baloxavir is effective in shortening the duration of influenza symptoms compared with NAIS in patients with influenza virus infection. However, most studies of baloxavir have focused on immunocompetent influenza patients, further studies are needed to confirm the efficacy and safety of baloxavir in immunocompromised hosts.

CAPSTONE-2 and FLAGSTONE were all randomized controlled trails of baloxavir, both studies had large sample size, and the research data were reliable. The CAPSTONE-2 study found that single-dose baloxavir has similar efficacy to oseltamivir for ameliorating influenza symptoms in high-risk outpatients, while FLAGSTONE study proved that the addition of baloxavir to standard-of-care NAI did not result in superior clinical outcomes compared with NAI alone in severely ill hospitalised patients with influenza. Both of the requested studies included some immunocompromised patients and patients with structural lung diseases, but no subgroup analysis was performed. In our proposed research, we would conduct secondary analyses based on data from these two randomized controlled trials, targeting immunosuppressed patients and patients with structural lung disease with influenza infections to evaluate the efficacy of barloxavir compared with oseltamivir and NAIs+Baloxavir vs NAIs.

The primary endpoint of the secondary analysis of FLAGSTONE study would be time to clinical improvement, other endpoints such as time to clinical response, clinical response rate, ICU admission rate, clinical failure rate, would also be assessed. The main outcome of the secondary analysis of CAPSTONE-2 study would be time to improvement of influenza symptoms, other outcomes such as time to alleviation of symptoms; number of influenza associated complications, number of antibiotic prescriptions, time to cessation of viral shedding, would be assessed, too.

Requested Studies:

A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Patients With Influenza at High Risk of Influenza Complications
Data Contributor: Roche
Study ID: NCT02949011
Sponsor ID: 1602T0832

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 Participants With Severe Influenza
Data Contributor: Roche
Study ID: NCT03684044
Sponsor ID: CP40617