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

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 herlegal/authorized representative

• Age greater than or equal to 18 years at the time of signing the Informed ConsentForm/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 apolymerase chain reaction (PCR)-based diagnostic assay.

• Presence of (a) fever (≥38.0 °C per tympanic or rectal thermometer; ≥ 37.5 °C peraxillary, oral or forehead/temporal thermometer) or (b) any influenza symptoms (cough, sore throat, nasal congestion, headache, feverishness or chills, muscle orjoint pain, fatigue).

• The time interval between the diagnosis of influenza and the pre-dose examinationsis 48 hours or less.

• For women of childbearing potential: Agreement to remain abstinent (refrain fromheterosexual 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 studytreatment. Hormonal contraceptive methods must be supplemented by a barrier method.A woman is considered to be of childbearing potential if she is postmenarcheal, hasnot reached a postmenopausal state greater than or equal to 12 continuous months ofamenorrhea with no identified cause other than menopause), and has not undergonesurgical sterilization (removal of ovaries and/or uterus). Examples of contraceptivemethods with a failure rate of < 1% per year include bilateral tubal ligation, malesterilization, hormonal contraceptives that inhibit ovulation, hormone-releasingintrauterine devices, and copper intrauterine devices. The reliability of sexualabstinence should be evaluated in relation to the duration of the clinical trial andthe preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are notacceptable methods of contraception.

Exclusion Criteria:

• Patients who have received more than 48 hours of antiviral treatment for the currentinfluenza 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 hoursprior to or during screening (according to local laboratory reference ranges: ALT orAST level > 5 times the upper limit of normal (ULN) OR ALT or AST > 3 times the ULNand total bilirubin level > 2 times the ULN

• Pregnant or breastfeeding, or positive pregnancy test in a predose examination, orintending to become pregnant during the study or within 28 days after the last doseof study treatment

• Exposure to an investigational drug within 5 half-lives or 30 days (whichever islonger) of randomization

• Any serious medical condition or abnormality in clinical laboratory tests that, inthe investigator's judgment, precludes the patient's safe participation in andcompletion 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