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

NCT05170009 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-12023076
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza

Keywords

Influenza; Bone marrow transplant; Flu; Baloxavir Marboxil; Xofluza; Oseltamivir

Outcome Measures

Primary Outcomes (3)

• Change of Influenza Viral RNA Loads From Baseline at the End of Treatment as Measured by Quantitative Real Time Polymerase Chain Reaction.

  Influenza viral RNA loads will be measured by quantitative real time polymerase chain reaction.

  Baseline; Day 10

• Between-treatment-arm Difference in the Change of Influenza Viral RNA Loads From Baseline at the End of Treatment as Measured by Quantitative Real Time Polymerase Chain Reaction.

  Influenza viral load will be measured by the quantitative real time polymerase chain reaction.

  Baseline; Day 10

• Between-treatment-arm Difference in the Change of Influenza Viral RNA Loads From Baseline at the End of Treatment as Measured by Influenza Plaque Assay (Replicating Virus).

  Influenza viral load will be measured by the influenza plaque assay.

  Baseline; Day 10

Secondary Outcomes (11)

• Change of Influenza Viral RNA Load From Baseline at Day 4 and Day 7 and 10 in Each Treatment Arm

  Baseline; Day 4; Day 7; Day 10

• Difference in Change of Influenza Viral Loads From Baseline at Day 4, 7 and 10 Between the Two Treatment Arms as Measured by Quantitative Real Time Polymerase Chain Reaction

  Baseline; Day 4; Day 7; Day 10

• Change of Influenza Viral Loads From Baseline at Day 4, 7 and 10 as Measured by Influenza Plaque Assay (Replicating Virus) in Each Treatment Arm

  Baseline; Day 4; Day 7; Day 10

• Difference in Change of Influenza Viral Loads From Baseline at Day 4, 7 and 10 Between the Two Treatment Arms as Measured by Influenza Plaque Assay (Replicating Virus)

  Baseline; Day 4; Day 7; Day 10

• Time to Improvement of Individual Influenza Symptoms as Assessed by Patient-reported Outcome Measures on a Single Scale

  Baseline to Day 30

Study Arms (2)

Active and standard of care

ACTIVE COMPARATOR

Active Baloxavir Marboxil and standard of care Oseltamivir

Drug: Baloxavir Marboxil; Drug: Oseltamivir

Placebo and standard of care

PLACEBO COMPARATOR

Placebo-matched Baloxavir Marboxil and standard of care Oseltamivir

Drug: Placebo; Drug: Oseltamivir

Interventions

Baloxavir Marboxil 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.

Also known as: Xofluza

Active and standard of care

Placebo DRUG

Placebo at baseline, day 4, and day 7.

Placebo and standard of care

Oseltamivir DRUG

Oseltamivir 75 mg twice daily for 10 days.

Also known as: Tamiflu

Active and standard of care; Placebo and standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Publications (18)

• Burnham P, Khush K, De Vlaminck I. Myriad Applications of Circulating Cell-Free DNA in Precision Organ Transplant Monitoring. Ann Am Thorac Soc. 2017 Sep;14(Supplement_3):S237-S241. doi: 10.1513/AnnalsATS.201608-634MG.

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• De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.

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• Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM; Centers for Disease Control and Prevention (CDC). Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 21;60(1):1-24.

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• Fukao K, Ando Y, Noshi T, Kitano M, Noda T, Kawai M, Yoshida R, Sato A, Shishido T, Naito A. Baloxavir marboxil, a novel cap-dependent endonuclease inhibitor potently suppresses influenza virus replication and represents therapeutic effects in both immunocompetent and immunocompromised mouse models. PLoS One. 2019 May 20;14(5):e0217307. doi: 10.1371/journal.pone.0217307. eCollection 2019.

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• Fukao K, Noshi T, Yamamoto A, Kitano M, Ando Y, Noda T, Baba K, Matsumoto K, Higuchi N, Ikeda M, Shishido T, Naito A. Combination treatment with the cap-dependent endonuclease inhibitor baloxavir marboxil and a neuraminidase inhibitor in a mouse model of influenza A virus infection. J Antimicrob Chemother. 2019 Mar 1;74(3):654-662. doi: 10.1093/jac/dky462.

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Related Links

• Influenza Antiviral Medications: Summary for Clinicians

MeSH Terms

Conditions

Influenza, Human

Interventions

baloxavir; Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

Due to change in patterns of respiratory viruses, and low or no flu circulating, we were unable to enroll the target number of participants. The only participants enrolled were the 2 in the placebo arm, 1 of whom withdrew early on. No comparison is possible with only 1 placebo participant.

Results Point of Contact

• Title: Dr. Mirella Salvatore
• Organization: Weill Cornell Medicine

mis2053@med.cornell.edu

(646) 318-8506

Study Officials

• Mirella Salvatore, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: December 27, 2021
• Study Start: April 22, 2022
• Primary Completion: January 17, 2024
• Study Completion: February 7, 2024
• Last Updated: February 26, 2025
• Results First Posted: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)