Baloxavir Marboxil for Flu

(Pebblestone Trial)

Recruiting at41 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Hoffmann-La Roche

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Severe influenza, Immunocompromised, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a flu medicine called baloxavir marboxil in children aged 1 to under 12 years. The medicine is given as a single dose and aims to stop the flu virus from spreading in the body, making the illness less severe and shorter. Baloxavir marboxil has been shown to reduce the duration of influenza symptoms by approximately one day.

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 Baloxavir Marboxil safe for human use?

Baloxavir Marboxil, also known as Xofluza, has been approved in the United States for treating influenza, especially in those at high risk of complications, indicating it has undergone safety evaluations for this use. ^{1 2 3 4 5}

How is the drug Baloxavir Marboxil unique for treating the flu?

Baloxavir Marboxil is unique because it is a first-in-class drug that works by inhibiting a specific protein in the flu virus, stopping it from replicating. It is taken as a single oral dose and can reduce the flu virus more quickly than some other treatments, like oseltamivir. ^{6 7 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Baloxavir Marboxil (Anti-viral)

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.

Participant Groups

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).

Baloxavir Marboxil is already approved in Japan for the following indications:

Approved in Japan as Xofluza for:

• Influenza A and B virus infections

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

Findings from Research

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis. [2020]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Influenza Therapeutics in Clinical Practice-Challenges and Recent Advances. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of baloxavir marboxil compared to laninamivir for the treatment of influenza in Japan. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of baloxavir marboxil on household transmission of influenza infection. [2022]

10. England 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. [2022]