Baloxavir + Oseltamivir for Flu

(COMBO 1 Trial)

Recruiting at 2 trial locations

Overseen By Daniel Freilich, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Bassett Healthcare

Must be taking: Oseltamivir

Must not be taking: Baloxavir

Disqualifiers: ESRD, Severe hepatic insufficiency, others

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

Compensation: Varies

Number of Visits: 1

Duration: 5 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled Phase 2-like, investigator-directed trial of hospitalized patients with laboratory confirmed influenza. Eligible and consented patients will be randomly assigned, in a 1:1 ratio, to one of two groups: Group 1, the combination treatment group (oseltamivir and baloxavir); Group 2, the standard treatment group (oseltamivir and placebo).

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used other influenza medications in the week before joining the trial, except for the initial oseltamivir dose given during this hospitalization.

Is the combination of Baloxavir and Oseltamivir safe for humans?

Baloxavir and Oseltamivir are generally well-tolerated in humans, with studies showing that Baloxavir has a comparable safety profile to other flu treatments like Oseltamivir. Baloxavir has been shown to be safe in both adults and children, with fewer drug-related side effects compared to Oseltamivir. ^{1 2 3 4 5}

How is the drug combination of Baloxavir and Oseltamivir for flu different from other treatments?

The combination of Baloxavir and Oseltamivir is unique because Baloxavir works by blocking a specific protein needed for the flu virus to multiply, while Oseltamivir prevents the virus from spreading to other cells. This dual approach may offer a more comprehensive treatment, especially for severe flu cases, compared to using either drug alone. ^{3 4 5 6 7}

What data supports the effectiveness of the drug Baloxavir for treating the flu?

Baloxavir has been approved in Japan for treating influenza A and B, as it effectively stops the flu virus from multiplying by blocking a key step in its replication process. ^{8 9 10 11 12}

Who Is on the Research Team?

daniel freilich, MD

Principal Investigator

Bassett Medical Center

Are You a Good Fit for This Trial?

Adults over 18, weighing more than 40 kg, hospitalized with confirmed flu who haven't taken other flu meds in the past week can join. They must be able to follow up for 30 days and take a test dose of oseltamivir within an hour. Pregnant women or those not using reliable contraception are excluded.

Inclusion Criteria

I weigh more than 40 kg.

I am starting or have just started Oseltamivir as prescribed.

I can start the study drug within 8 hours of being admitted for flu treatment.

Exclusion Criteria

I have severe liver problems.

I cannot take pills by mouth due to nausea or risk of inhaling them.

I have chosen not to take oseltamivir as my initial treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive oseltamivir and either baloxavir or placebo for 5 days

5 days

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Visits on days 1, 2, 3, 4, 7, and 30

What Are the Treatments Tested in This Trial?

Interventions

• Baloxavir
• Oseltamivir

Trial Overview The COMBO Trial compares two treatments for hospitalized flu patients: one group receives both oseltamivir and baloxavir, while the other gets oseltamivir with a placebo. Patients are randomly assigned to either group in equal numbers.

How Is the Trial Designed?

Group I: baloxavir Experimental Treatment 1 Intervention

Baloxavir: 40 mg po once for wt \< 80 kg OR 80 mg po once for wt \>/= 80 kg

Group II: placebo Placebo Group 1 Intervention

placebo po once

Baloxavir is already approved in United States, Japan 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
• Post-exposure prophylaxis of influenza in persons aged ≥5 years within 48 hours of contact with an individual with influenza

Approved in Japan as Xofluza for:

• Treatment of influenza virus infection

Who Is Running the Clinical Trial?

Bassett Healthcare

Lead Sponsor

Trials

23

Recruited

1,400+

Viroclinics Biosciences B.V.

Industry Sponsor

Trials

2

Recruited

290+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Viroclinics Biosciences B.V.

Collaborator

Trials

2

Recruited

290+

Published Research Related to This Trial

In a study of 136 virologically suppressed Asian participants living with HIV, switching to the regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) resulted in 100% virological suppression at week 48, with no treatment-emergent drug resistance observed.

The safety profile of B/F/TAF was comparable to that of participants who continued their baseline regimens, with no serious adverse events reported and a significant reduction in tubular proteinuria for those switching from tenofovir disoproxil fumarate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials. Avihingsanon, A., Chetchotisakd, P., Kiertiburanakul, S., et al.[2023]

In a phase 2 study involving initial antiretroviral therapy, both bictegravir and dolutegravir combined with emtricitabine and tenofovir alafenamide demonstrated excellent efficacy over 60 weeks.

After switching to a single-tablet regimen of bictegravir, all participants maintained viral suppression for 12 weeks in the open-label phase, indicating the treatment's safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. Sax, PE., DeJesus, E., Crofoot, G., et al.[2019]

In a 48-week study involving 86 older adults with HIV, switching to the medication bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) resulted in a high rate of virologic suppression, with 90.7% of participants maintaining HIV-1 RNA levels below 50 copies/ml.

The treatment was well tolerated, with no serious adverse events related to the drug and a high adherence rate of 98.6%, indicating that B/F/TAF is a safe and effective option for older adults living with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial. Maggiolo, F., Rizzardini, G., Molina, JM., et al.[2021]

Baloxavir marboxil (Xofluza™) is an oral medication that effectively inhibits the influenza virus by blocking the initiation of mRNA synthesis, which is crucial for the virus's replication.

The drug received its first global approval in Japan in February 2018 for treating influenza A or B infections, and further Phase III trials are ongoing in the USA, EU, and other regions to support its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baloxavir: First Global Approval. Heo, YA.[2020]

In a 96-week study involving 86 older adults (≥65 years) living with HIV, switching to the treatment B/F/TAF maintained high rates of viral suppression, with 94.2% of participants remaining virologically suppressed at week 72 and 74.4% at week 96.

The treatment was found to be safe, with no serious drug-related adverse events and stable CD4 counts, indicating that B/F/TAF is a viable long-term option for older adults with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age. Maggiolo, F., Rizzardini, G., Molina, JM., et al.[2023]

In a study of 45 pediatric patients under 12 years old, baloxavir marboxil at a higher dose of 2 mg/kg was found to be well tolerated, with a safety profile similar to the lower dose of 1 mg/kg, despite 53.3% experiencing mild adverse events like nasopharyngitis and diarrhea.

The treatment effectively reduced influenza symptoms, with a median time to illness alleviation of 37.8 hours and fever resolution in 22.0 hours, indicating that the higher dose does not compromise efficacy compared to the standard dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children Sonoyama, T., Sakaguchi, H., Koshimichi, H., et al.[2021]

Baloxavir marboxil significantly reduced the time to alleviate influenza symptoms and the time to cessation of viral shedding compared to zanamivir and oseltamivir, indicating its superior efficacy in treating influenza.

In terms of safety, baloxavir showed a lower incidence of drug-related adverse events compared to oseltamivir and laninamivir, suggesting it is a safer option among antiviral treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A network meta-analysis of the efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors for the treatment of influenza in otherwise healthy patients. Taieb, V., Ikeoka, H., Ma, FF., et al.[2020]

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]

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 246 patients with influenza A, baloxavir marboxil was found to significantly reduce the duration of fever compared to oseltamivir, indicating its efficacy as an antiviral treatment (P < 0.001).

Both baloxavir and oseltamivir showed similar overall effectiveness in managing symptoms and health-related quality of life, suggesting that baloxavir is a viable alternative to oseltamivir for treating influenza A in Chinese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China. Liao, G., Xia, M., Jiang, Y., et al.[2023]

Baloxavir marboxil, a prodrug that inhibits viral replication, shows no clinically significant drug-drug interaction when administered with oseltamivir, suggesting they can be safely combined for treating severe influenza.

In a study involving 18 healthy adults, both drugs maintained their effectiveness without altering each other's plasma concentrations, and any reported side effects were mild and unrelated to the medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Drug-Drug Interaction Potential between Baloxavir Marboxil and Oseltamivir in Healthy Subjects. Kawaguchi, N., Koshimichi, H., Ishibashi, T., et al.[2021]

Baloxavir marboxil is a single-dose antiviral medication that works by inhibiting cap-dependent endonuclease, which is crucial for viral transcription, making it a convenient option for treating influenza in outpatients.

Its safety profile is similar to that of oseltamivir, but there is a risk of developing resistance, which is an important consideration for its use in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza. Abraham, GM., Morton, JB., Saravolatz, LD.[2021]

Citations

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

Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. [2019]

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

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial. [2021]

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

Baloxavir: First Global Approval. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age. [2023]

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

Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children [2021]

7. England pubmed.ncbi.nlm.nih.gov

A network meta-analysis of the efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors for the treatment of influenza in otherwise healthy patients. [2020]

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

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

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China. [2023]

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

Evaluation of Drug-Drug Interaction Potential between Baloxavir Marboxil and Oseltamivir in Healthy Subjects. [2021]

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

Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza. [2021]