Baloxavir + Oseltamivir for Severe Flu
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Influenza antivirals, Herbal therapies
Disqualifiers: Mechanical ventilation, Age under 12, Pregnancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This phase II trial studies the effect of baloxavir in combination with oseltamivir in treating severe influenza infection in patients who have previously received a hematopoietic (blood) stem cell transplant or have a hematological malignancy. Baloxavir is an antiviral drug that inhibits the growth of influenza virus, reduces viral load and prevents further influenza infection. Osetamivir is an antiviral drug that blocks enzymes on the surfaces of influenza viruses, interfering with cell release of complete viral particles. Giving baloxavir in combination with oseltamivir may shorten or decrease the intensity of influenza infection compared to oseltamivir alone.
Will I have to stop taking my current medications?
You may need to stop taking certain medications. The trial does not allow the use of other influenza antiviral drugs besides oseltamivir and baloxavir, and herbal therapies are also prohibited.
Is the combination of Baloxavir and Oseltamivir safe for humans?
Oseltamivir (Tamiflu) has been used safely in over 11,000 people, including children and the elderly, with the main side effect being mild stomach upset, which can be reduced by taking it with food. No major safety concerns have been found that would limit its use for treating and preventing the flu.12345
How is the drug combination of Baloxavir and Oseltamivir unique for treating severe flu?
The combination of Baloxavir and Oseltamivir is unique because it uses two different mechanisms to fight the flu virus: Baloxavir blocks the virus from multiplying by inhibiting a key enzyme, while Oseltamivir prevents the virus from spreading by stopping it from leaving infected cells. This dual approach may enhance the treatment's effectiveness, especially in severe cases.678910
Eligibility Criteria
This trial is for adults with severe flu who've had a blood stem cell transplant or have blood cancer. They must show signs of lower respiratory tract infection (LRTI) or be at high risk due to weakened immunity. Participants need confirmed influenza and can't be on certain antiviral drugs, unable to take oral meds, pregnant, under 12 years old, unable to consent, or require mechanical breathing support.Inclusion Criteria
I have a lung infection confirmed by imaging, bronchoscopy, or biopsy.
I have a severe lung infection or a serious upper respiratory infection.
I have a high-risk upper respiratory infection without lung involvement, with a weak immune system or very low white blood cell counts.
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Exclusion Criteria
Patient requires mechanical ventilation at time of enrollment
I am able to give my consent for treatment.
I am not taking certain flu drugs or herbal treatments.
See 3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive oseltamivir orally twice daily for up to 10 days and baloxavir marboxil every 72 hours for a total of 3 doses
10 days
Daily visits for medication administration
Follow-up
Participants are monitored for changes in influenza viral loads and other health outcomes
30 days
Follow-up visits on days 0, 1, 3, 7, 14, and 30
Treatment Details
Interventions
- Baloxavir Marboxil (Antiviral)
- Oseltamivir (Antiviral)
Trial OverviewThe study tests if combining two antiviral drugs—Baloxavir and Oseltamivir—is more effective in treating severe flu in immunocompromised patients than using Oseltamivir alone. Baloxavir reduces viral growth while Oseltamivir blocks virus spread from infected cells.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (oseltamivir, baloxavir marboxil)Experimental Treatment2 Interventions
Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
Group II: Arm II (oseltamivir)Active Control1 Intervention
Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Safety and pharmacology of oseltamivir in clinical use. [2020]Oseltamivir is a novel agent approved for the treatment and prevention of influenza infection and illnesses in adults and children. Assessment of data from the clinical trial programme, a US health insurance database study and postmarketing surveillance allowed a comprehensive review of the safety of oseltamivir in clinical use in subjects >1 year of age. Oseltamivir has been studied over the course of a 5-year development programme in >11000 subjects from North America, Europe and the Southern Hemisphere, including otherwise healthy adults, approximately 500 elderly/high-risk subjects, and children (>1000) aged 1-12 years. Safety evaluations included treatment-emergent adverse events, hospitalisations and deaths, as well as haematological and biochemical laboratory safety tests. The data reveals that oseltamivir has simple, uncomplicated pharmacology and lacks potential for drug-drug interactions. Electrocardiogram parameters, including corrected QT interval, were unaffected by oseltamivir even at high doses. Postmarketing studies confirmed that transient gastrointestinal disturbance is the major adverse effect of oseltamivir and that this can be reduced by taking oseltamivir after a light snack. On treatment serious adverse events were reported in 1.3% of oseltamivir 75mg twice daily, 0.7% of oseltamivir 150 mg twice daily and 1.2% of placebo recipients, respectively, in the clinical trial programme. Postmarketing, it is estimated that, to date, over 4 million oseltamivir prescriptions have been dispensed worldwide. Approximately 2300 spontaneous reports were received by the manufacturer over the three winter seasons of use. As these events are reported infrequently and from an unknown number of users, it is not possible to definitively assess causality or frequency of reported events. Most reports were of gastrointestinal and skin reactions. However, a clear association between the skin reactions and oseltamivir has not been established. A large study of insurance records, which permitted the assessment of the relative risk of medical events treated in the month following prescription of oseltamivir in general use, showed no evidence of increased risk of cardiac, neuropsychiatric or respiratory events for those receiving oseltamivir compared with those who did not. To conclude, no important safety concerns have evolved which might limit the suitability of oseltamivir for the treatment and prevention of influenza in all patient populations.
Transplacental transfer of oseltamivir and its metabolite using the human perfused placental cotyledon model. [2022]Given the lack of data regarding the use of oseltamivir (Tamiflu) during pregnancy, we aimed to evaluate the placental transfer of oseltamivir phosphate and its active metabolite oseltamivir carboxylate, using the perfused placental cotyledon model.
A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population. [2022]To evaluate the efficacy and safety of oseltamivir treatment in a population at high risk for influenza.
Stability of oseltamivir in various extemporaneous liquid preparations. [2013]The purpose of this study was to determine the stability of oseltamivir, the active ingredient in Tamiflu, in contemporaneously compounded suspensions for a period of not less than 90 days. The suspension vehicles provided for the study were chosen because of ease of preparation, commercial availability, and palatability. Stability of the active ingredient was demonstrated for suspensions prepared in PCCA-Plus, PCCA Acacia, and 1% methylcellulose and was independent of storage temperature (tested temperatures were 2 deg C to 8 deg C and 25 deg C). A control sample of the commercial liquid form of Tamiflu was prepared, stored and analyzed along with the samples prepared from the contents of capsules. There was no difference in the apparent stability of the two forms of the drug preparation.
Oseltamivir carboxylate, the active metabolite of oseltamivir phosphate (Tamiflu), detected in sewage discharge and river water in Japan. [2021]Oseltamivir phosphate (OP; Tamiflu) is a prodrug of the anti-influenza neuraminidase inhibitor oseltamivir carboxylate (OC) and has been developed for the treatment and prevention of both A and B strains of influenza. The recent increase in OP resistance in influenza A virus (H1N1; commonly called "swine flu") has raised questions about the widespread use of Tamiflu in seasonal epidemics and the potential ecotoxicologic risk associated with its use in the event of a pandemic.
Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. [2021]ADVANCE compared the efficacy and safety of two antiretroviral first-line combinations (dolutegravir combined with emtricitabine and either tenofovir disoproxil fumarate or tenofovir alafenamide), with a third regimen (efavirenz combined with emtricitabine and tenofovir disoproxil fumarate) previously recommended by WHO. Here, we report the 96-week data for the study.
Pharmacokinetics and safety of coadministered oseltamivir and rimantadine in healthy volunteers: an open-label, multiple-dose, randomized, crossover study. [2013]Preclinical data suggest increased antiviral activity and less viral resistance when neuraminidase inhibitors and adamantanes are used in combination to harness the complementary effects of their different mechanisms of action. Healthy volunteers were randomized to 5-day oral treatment with oseltamivir 75 mg or rimantadine 100 mg twice daily as monotherapy or to combination treatment. Each participant received all 3 regimens in 1 of 6 treatment sequences, with a minimum of 7 days' washout between periods. Final follow-up was 10 to 14 days after the final dose. Drug exposure, elimination, safety, and tolerability were assessed. There were no clinically relevant differences in 12-hour areas under the concentration-time curves of drug in plasma or peak plasma drug concentrations with combination versus monotherapy. Elimination half-life was unaffected by coadministration. There were no safety/tolerability concerns. One case of vomiting and 1 of paresthesia were considered remotely related to combination treatment, and 1 episode of toothache and 1 of acne were considered unrelated. There were no serious adverse events and no deaths. Combination therapy with oseltamivir and rimantadine at recommended dosages in adults had no discernible effect on the pharmacokinetics of either drug and raised no tolerability issues.
Rates and predictors of switching to tenofovir alafenamide-containing ART in a nationwide cohort. [2022]Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function.
Baloxavir: First Global Approval. [2020]Baloxavir marboxil (Xofluza™; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections. Phase III development is underway in the USA, EU and other countries for this indication. This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.
Combination of baloxavir and oseltamivir for treatment of severe influenza infection in hematopoietic cell transplant recipients: a novel treatment strategy for a high-risk population. [2022]Baloxavir, a cap-dependent endonuclease inhibitor, was recently approved for treatment of severe influenza infections. Combining baloxavir with oseltamivir has been proposed to increase the response rate. We report 2 hematopoietic cell transplant recipients with severe influenza infections who were treated with this combination and discuss possible reasons for their different responses.