Baloxavir in Combination With Oseltamivir in Allogenic Bone Marrow Transplant Recipients With Influenza

NCT ID: NCT05170009

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-22
• Study Completion Date: 2024-02-07

Brief Summary

This is a randomized, double-blind, placebo-controlled pilot study of the efficacy and safety of baloxavir in combination with oseltamivir (standard of care) for the treatment of influenza in allogeneic stem cell transplant patients. Although there are no data about this treatment option currently available, the investigator hypothesizes that combination therapy may be more effective in clearing influenza virus infection and decreasing the rate of emergence of resistant influenza in immunocompromised human hosts.

Detailed Description

This is a randomized double-blind placebo-controlled pilot study of the efficacy and safety of baloxavir in combination with oseltamivir (standard of care) for the treatment of influenza in allogeneic stem cell transplant patients. 30 SCT recipients will take part in the study. Participants with be randomly assigned (1:1) to either baloxavir + oseltamivir or baloxavir-matched placebo +oseltamivir. Before randomization, patients will be stratified by hospitalization status and influenza type A (yes/no).

Patients in the baloxavir combination arm will receive weight-adjusted baloxavir (40 mg for patients weighing <80 kg and 80 mg for those weighing ≥80 kg) at baseline and at day 4 and day 7. They will also receive oseltamivir 75 mg twice daily for 10 days. Patients in the baloxavir-matched placebo + oseltamivir arm will receive baloxavir-matched placebo at baseline and at day 3 and day 7and oseltamivir 75 mg twice daily for 10 days.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active and standard of care

Active Baloxavir Marboxil and standard of care Oseltamivir

Group Type: ACTIVE_COMPARATOR

Baloxavir Marboxil

Intervention Type: DRUG

Weight-adjusted Baloxavir Marboxil (40 mg for patients weighing \<80 kg and 80 mg for those weighing ≥80 kg) at baseline, day 4, and day 7.

Oseltamivir

Intervention Type: DRUG

Oseltamivir 75 mg twice daily for 10 days.

Placebo and standard of care

Placebo-matched Baloxavir Marboxil and standard of care Oseltamivir

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo at baseline, day 4, and day 7.

Oseltamivir

Intervention Type: DRUG

Oseltamivir 75 mg twice daily for 10 days.

Interventions

Baloxavir Marboxil

Weight-adjusted Baloxavir Marboxil (40 mg for patients weighing \<80 kg and 80 mg for those weighing ≥80 kg) at baseline, day 4, and day 7.

Intervention Type: DRUG

Placebo

Placebo at baseline, day 4, and day 7.

Intervention Type: DRUG

Oseltamivir

Oseltamivir 75 mg twice daily for 10 days.

Intervention Type: DRUG

Other Intervention Names

Xofluza; Tamiflu

Eligibility Criteria

Inclusion Criteria

• Adult patients: Signed informed consent by any patient capable of giving consent, or, where the patient is not capable of giving consent, by his or her legal/authorized representative
• Age greater than or equal to 18 years at the time of signing the Informed Consent Form/Assent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Have received allogeneic bone marrow transplant
• Tested positive for influenza infection after the onset of symptoms using a polymerase chain reaction (PCR)-based diagnostic assay.
• Presence of (a) fever (≥38.0 °C per tympanic or rectal thermometer; ≥ 37.5 °C per axillary, oral or forehead/temporal thermometer) or (b) any influenza symptoms (cough, sore throat, nasal congestion, headache, feverishness or chills, muscle or joint pain, fatigue).
• The time interval between the diagnosis of influenza and the pre-dose examinations is 48 hours or less.
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse):
• Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 28 days after the last dose of study treatment. Hormonal contraceptive methods must be supplemented by a barrier method. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state greater than or equal to 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria

• Patients who have received more than 48 hours of antiviral treatment for the current influenza infection prior to screening
• Patients who have received Baloxavir for the current influenza infection
• Known contraindication to neuraminidase inhibitors
• Patients weighing < 40 kg
• Patients unable to swallow tablets
• Patients with known severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis
• Patients with any of the following laboratory abnormalities detected within 24 hours prior to or during screening (according to local laboratory reference ranges: ALT or AST level > 5 times the upper limit of normal (ULN) OR ALT or AST > 3 times the ULN and total bilirubin level > 2 times the ULN
• Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or intending to become pregnant during the study or within 28 days after the last dose of study treatment
• Exposure to an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Known hypersensitivity to baloxavir marboxil or the drug product excipients
• Known COVID-19 coinfection
• Unwilling to undergo nasopharyngeal (NP) swabs as per study schedule

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mirella Salvatore, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine

New York, New York, United States

Countries

United States

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.cdc.gov/flu/hcp/antivirals/summary-clinicians.html?CDC_AAref_Val=https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm

Influenza Antiviral Medications: Summary for Clinicians

Other Identifiers

20-12023076

Identifier Type: -

Identifier Source: org_study_id