Baloxavir Marboxil for Flu

(Pebblestone Trial)

Recruiting at 45 trial locations

Overseen By Reference Study ID Number: CV44536 https://forpatients.roche.com/

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Severe influenza, Immunocompromised, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 1 day

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a flu treatment called baloxavir marboxil in children under 12 with the flu. The first part examines how the flu virus changes in these children after treatment. The second part assesses how often these children spread the flu to family members. A suitable candidate for the trial is a child with flu symptoms confirmed by a test within the last 48 hours and no recent history of COVID-19. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking flu treatment for children.

Will I have to stop taking my current medications?

The trial requires that you have not taken certain flu medications like baloxavir marboxil, oseltamivir, or others within 30 days before joining. If you're on these, you might need to stop them before participating.

Is there any evidence suggesting that baloxavir marboxil is likely to be safe for children under 12 years with influenza?

Previous studies have shown that baloxavir marboxil is safe for treating the flu. Common side effects include vomiting and diarrhea, with about 5% of participants experiencing these. Vomiting was more frequent, affecting around 18% of those who took the medication. Although these side effects can be uncomfortable, they are usually manageable and not severe.

Limited safety information exists for children aged 5 to under 12 years who are at high risk of flu complications. However, baloxavir marboxil is approved for treating the flu in other age groups, suggesting it is generally well-tolerated.

Overall, while some side effects may occur, research indicates that baloxavir marboxil is a relatively safe option for flu treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for flu?

Baloxavir Marboxil is unique because it targets the flu virus in a novel way. Unlike traditional antiviral treatments like oseltamivir, which inhibit the virus from spreading, baloxavir marboxil works by blocking the cap-dependent endonuclease enzyme. This stops the virus from replicating its genetic material. Researchers are excited because this mechanism can potentially lead to faster symptom relief and a single-dose regimen, making it more convenient and possibly more effective in reducing virus transmission.

What evidence suggests that baloxavir marboxil is effective for treating influenza in children?

Research has shown that baloxavir marboxil, which participants in this trial will receive, effectively treats the flu. In previous studies, a single dose of baloxavir helped people recover 42% faster than those who took a placebo, a pill with no medicine. It eases symptoms and reduces the chance of spreading the flu to others. Studies found that people treated with baloxavir were less likely to pass the flu to those around them. This makes baloxavir a promising choice for both treating the flu and preventing its spread. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This study is for children aged 1 to under 12 with confirmed influenza, who've shown symptoms within the last 48 hours and tested negative for COVID-19. They shouldn't have taken certain antiviral drugs recently or be severely immunocompromised. Girls who have started their periods are excluded.

Inclusion Criteria

You need to have a negative test for the coronavirus within 48 hours before the study screening.

I have symptoms like the flu and tested positive for it within the last day.

The time interval between the onset of influenza symptoms and the pre-dose examinations at screening is 48 hours or less

Exclusion Criteria

Treatment with an investigational therapy within 30 days or 5 half-lives, whichever is longer, prior to screening.

Known hypersensitivity to baloxavir marboxil or the drug product excipients.

I am hospitalized due to a severe flu infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of baloxavir marboxil on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Up to Day 29

What Are the Treatments Tested in This Trial?

Interventions

• Baloxavir Marboxil

Trial Overview

The trial tests how well Baloxavir Marboxil works before and after a single dose in treating young patients with the flu. It aims to monitor changes in susceptibility to this medication post-treatment.

How Is the Trial Designed?

Group I: Baloxavir Marboxil Experimental Treatment 1 Intervention

Participants will receive a single oral dose of baloxavir marboxil on Day 1 (based on body weight and age). HHCs related to IPs will be enrolled but will not receive treatment.

Baloxavir Marboxil is already approved in United States, Japan, European Union for the following indications:

Approved in United States as Xofluza for:

• Acute uncomplicated influenza within 2 days of illness onset in people aged ≥5 years who are otherwise healthy, or in people aged ≥12 years who are at high risk of developing influenza-related complications

Approved in Japan as Xofluza for:

• Influenza A and B virus infections

Approved in European Union as Xofluza for:

• Treatment of uncomplicated influenza in adults and adolescents aged 12 years and older weighing at least 40 kg

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Baloxavir marboxil is a cost-effective antiviral treatment for influenza in otherwise healthy adults in Japan, showing a small gain in quality-adjusted life-years (QALYs) compared to laninamivir, with an incremental cost per QALY gained of ¥2,231,260, which is below the willingness-to-pay threshold of ¥5,000,000/QALY.

The study indicates that the additional costs of baloxavir are offset by avoided drug-related adverse events (DRAEs), and the probability of baloxavir being cost-effective is estimated at 64%, suggesting it may be a favorable option for influenza treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of baloxavir marboxil compared to laninamivir for the treatment of influenza in Japan. Skrzeczek, A., Ikeoka, H., Hirotsu, N., et al.[2021]

Baloxavir marboxil is an effective single-dose oral treatment for acute uncomplicated influenza in patients aged 12 and older, showing similar efficacy to oseltamivir and faster reduction of viral load.

It works by inhibiting the influenza virus's polymerase acidic protein, and while it is well tolerated, monitoring for resistant virus strains is important due to emerging variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza. Shirley, M.[2021]

In a study of 169 patients with influenza type A, the secondary attack rate of influenza among household members was 9.0% for those treated with baloxavir compared to 13.5% for those treated with oseltamivir, indicating that baloxavir is effective in reducing transmission.

The results suggest that baloxavir is a viable alternative to oseltamivir for treating influenza, as both medications showed comparable effectiveness in preventing household transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of baloxavir marboxil on household transmission of influenza infection. Umemura, T., Mutoh, Y., Kawamura, T., et al.[2022]

In a study involving 115,238 children aged 7-15 years, baloxavir marboxil did not lead to increased medical resource use compared to neuraminidase inhibitors (NAIs) within 9 days of treatment, indicating its safety in terms of healthcare-seeking behavior.

However, baloxavir was associated with higher medical resource use compared to oseltamivir, suggesting that while it is effective, it may lead to more follow-up care than this specific NAI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of baloxavir marboxil prescription with subsequent medical resource utilization among school-aged children with influenza. Takeuchi, M., Kawakami, K.[2021]

In a study of 4,490 children with influenza B treated in Japan, baloxavir marboxil was prescribed to 29.4% of patients, while neuraminidase inhibitors (NAIs) were used for 70.6%.

Baloxavir did not show a reduction in healthcare resource utilization compared to NAIs, indicating that it may not provide additional benefits in managing influenza B within 9 days of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Baloxavir Marboxil Prescription for Children with Influenza B Infections and Short-Term Healthcare Consumption in Japan During the 2018-2019 Influenza Season. Shinno, K., Takeuchi, M., Kawakami, K.[2022]

Lumacaftor-ivacaftor therapy has been shown to improve pulmonary function and reduce exacerbations in cystic fibrosis patients with the Phe-508del mutation, but it may also lead to side effects such as transaminitis and non-congenital cataracts.

The therapy can cause dyspnea in some patients, particularly at the start of treatment, and it has significant drug interaction risks due to lumacaftor's strong induction of CYP3A, which can affect the efficacy of other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis. Talamo Guevara, M., McColley, SA.[2018]

In a study of 12 patients with severe cystic fibrosis (ppFEV1 <40), the combination therapy of lumacaftor/ivacaftor (LUM/IVA) led to a significant decline in lung function (median relative change of -19% at 2 hours), although most patients recovered by 1 month.

A high percentage (83.3%) of patients experienced non-severe respiratory-related adverse events within 24 hours of starting LUM/IVA, indicating that close monitoring for adverse effects is necessary in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease. Popowicz, N., Wood, J., Tai, A., et al.[2018]

In a study of 845 cystic fibrosis patients treated with lumacaftor-ivacaftor, those who continued the treatment experienced significant improvements in lung function (ppFEV1 increased by +3.67%) and nutritional status (body mass index increased by +0.73 kg/m2).

However, 18.2% of patients discontinued treatment, primarily due to respiratory and nonrespiratory adverse events, with discontinuation linked to older age and poorer lung function, indicating that while the drug is effective for many, it may pose risks for certain individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis. Burgel, PR., Munck, A., Durieu, I., et al.[2020]

Lumacaftor and the metabolite ivacaftor-M6 significantly induce the activity of the enzyme CYP3A4, which could lead to reduced concentrations of ivacaftor in the body, potentially limiting its effectiveness.

While ivacaftor itself also induces CYP3A4, its other major metabolite (M1) and the new CFTR modulator tezacaftor do not show this effect, suggesting a complex interaction that may impact treatment outcomes for cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytochrome P450 3A4 Induction: Lumacaftor versus Ivacaftor Potentially Resulting in Significantly Reduced Plasma Concentration of Ivacaftor. Schneider, EK.[2020]

Baloxavir marboxil is a newly approved antiviral for treating influenza in high-risk patients, highlighting the progress in developing effective treatments for influenza-related complications.

Despite the approval of new antivirals, there is still a lack of licensed treatments specifically for severe or hospitalized influenza, indicating ongoing challenges in addressing this public health issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza Therapeutics in Clinical Practice-Challenges and Recent Advances. Beigel, JH., Hayden, FG.[2023]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40267424/

Efficacy of Baloxavir Treatment in Preventing Transmission ...

Treatment with a single oral dose of baloxavir led to a lower incidence of transmission of influenza virus to close contacts than placebo.

2.

roche.com

roche.com/media/releases/med-cor-2025-04-25

New England Journal of Medicine publishes phase III data ...

The trial met its primary endpoint, showing a single, oral dose of Xofluza taken by people infected with influenza reduced the odds of untreated ...

3.

nejm.org

nejm.org/doi/abs/10.1056/NEJMoa2413156

Efficacy of Baloxavir Treatment in Preventing Transmission ...

Treatment with a single oral dose of baloxavir led to a lower incidence of transmission of influenza virus to close contacts than placebo.

4.

xofluza-hcp.com

xofluza-hcp.com/efficacy/otherwise-healthy.html

XOFLUZA® (baloxavir marboxil) Otherwise Healthy Patients

42% (1.6 days) faster relief from flu symptoms (in patients aged 12 to 17 years) with single-dose XOFLUZA compared with placebo.1. For subjects aged 12 to 17 ...

5.

gene.com

gene.com/media/press-releases/15037/2024-09-18/positive-phase-iii-results-show-xofluza-

Genentech: Press Releases | Wednesday, Sep 18, 2024

Data from the CENTERSTONE study shows single-dose Xofluza reduces transmission of influenza from an infected person to household members.

6.

xofluza-hcp.com

xofluza-hcp.com/safety.html

Safety profile for flu treatment and post-exposure prophylaxis

There are limited safety data in patients 5 to <12 years at high risk of developing influenza complications.

7.

xofluza.com

xofluza.com/safety.html

Things you need to know about XOFLUZA safety

XOFLUZA does not prevent bacterial infections that may happen with the flu. It is not known if XOFLUZA is safe and effective for the treatment and prevention ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12107739/

Safety evaluation of baloxavir marboxil

As a novel anti-influenza agent, baloxavir marboxil lacks real-world safety data in large populations. Therefore, this study aimed to ...

9.

ema.europa.eu

ema.europa.eu/en/documents/product-information/xofluza-epar-product-information_en.pdf

Xofluza, INN-baloxavir marboxil - EMA

The predominant influenza virus strain in this study was the A/H3 subtype. The primary objective was to compare the safety of a single dose of baloxavir.

10.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/210854s023,214410s008lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION These ...

The most frequently reported AEs (≥ 5%) in all subjects in the XOFLUZA treatment arm were vomiting (5%) and diarrhea (5%). Vomiting was reported in 18% of ...