Study Summary
This trial will study whether a combination of two drugs is more effective than one drug at treating influenza in stem cell transplant patients.
Eligible Conditions
- Influenza
Treatment Effectiveness
Effectiveness Progress
Study Objectives
7 Primary · 12 Secondary · Reporting Duration: Baseline; Day 4; Day 7; Day 10
Baseline to Day 30
Therapeutic procedure
Percentage of patients with treatment-emergent variants of neuraminidase and polymerase by direct next-generation sequencing
Time to improvement of individual influenza symptoms as assessed by patient-reported outcome measures on a single scale
Time to viral clearance, as assessed by difference in Percentage of Participants Positive by RT-PCR at each time-point (in each treatment group)
Time to viral clearance, as assessed by difference in Percentage of Participants Positive by influenza plaque assay at each time-point (in each treatment group)
Time to viral clearance, as assessed by difference in Percentage of Participants Positive by quantitative real time polymerase chain reaction
Time to viral clearance, as assessed by time to sustained Cessation of Viral detection by RT-PCR up to day 30 defined as the time between the start of treatment and when virus titer will be below the detection limit on all subsequent sampling time points
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).
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.
Change of influenza viral RNA loads from baseline at the end of treatment as measured by quantitative real time polymerase chain reaction.
Orthomyxoviridae
Change of influenza viral load from baseline at the end of treatment as assessed by the change of the amount of influenza virus at day 10 measured by quantitative real time polymerase chain reaction (qRT-PCR, nucleic acid)
Day 10
Change of influenza viral RNA load from baseline at day 4 and day 7 and 10 in each treatment arm
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
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)
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
Day 15
Percentage of participants with adverse events (AEs)
Day 30
Percentage of patients who experience each influenza-related complications: hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically-confirmed pneumonia as an adverse event after the initiation of study treatment
Time to return to preinfluenza health status
Trial Safety
Safety Progress
This is further along than 68% of similar trials
Trial Design
2 Treatment Groups
Active and standard of care
1 of 2
Placebo and standard of care
1 of 2
Active Control
Non-Treatment Group
30 Total Participants · 2 Treatment Groups
Primary Treatment: Active and standard of care · Has Placebo Group · Phase 2 & 3
Active and standard of careActiveComparator Group · 2 Interventions: Oseltamivir, Baloxavir Marboxil · Intervention Types: Drug, Drug
Placebo and standard of carePlaceboComparator Group · 2 Interventions: Oseltamivir, Placebo · Intervention Types: Drug, Drug
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: baseline; day 4; day 7; day 10
Who is running the clinical trial?
Weill Medical College of Cornell UniversityLead Sponsor
986 Previous Clinical Trials
1,338,542 Total Patients Enrolled
Genentech, Inc.Industry Sponsor
1,497 Previous Clinical Trials
564,586 Total Patients Enrolled
Mirella Salvatore, MDPrincipal InvestigatorWeill Medical College of Cornell University
Eligibility Criteria
Age 18+ · All Participants · 8 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:You are able to comply with the study protocol.
You have received allogeneic bone marrow transplant.
References
- Lee, Nelson, and Michael G Ison. 2012. “Diagnosis, Management and Outcomes of Adults Hospitalized with Influenza”. Antiviral Therapy. SAGE Publications. doi:10.3851/imp2059.
- Muthuri, Stella G, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Tarig S A Al Khuwaitir, Adbullah Al Mamun, Ashish P Anovadiya, et al.. 2014. “Effectiveness of Neuraminidase Inhibitors in Reducing Mortality in Patients Admitted to Hospital with Influenza A H1n1pdm09 Virus Infection: A Meta-analysis of Individual Participant Data”. The Lancet Respiratory Medicine. Elsevier BV. doi:10.1016/s2213-2600(14)70041-4.
- Fukao, Keita, Yoshinori Ando, Takeshi Noshi, Mitsutaka Kitano, Takahiro Noda, Makoto Kawai, Ryu Yoshida, Akihiko Sato, Takao Shishido, and Akira Naito. 2019. “Baloxavir Marboxil, a Novel Cap-dependent Endonuclease Inhibitor Potently Suppresses Influenza Virus Replication and Represents Therapeutic Effects in Both Immunocompetent and Immunocompromised Mouse Models”. Edited by Stefan Pöhlmann. Plos One. Public Library of Science (PLoS). doi:10.1371/journal.pone.0217307.
- De Vlaminck, Iwijn, Hannah A. Valantine, Thomas M. Snyder, Calvin Strehl, Garrett Cohen, Helen Luikart, Norma F. Neff, et al.. 2014. “Circulating Cell-free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection”. Science Translational Medicine. American Association for the Advancement of Science (AAAS). doi:10.1126/scitranslmed.3007803.
- Hayden, Frederick G., Norio Sugaya, Nobuo Hirotsu, Nelson Lee, Menno D. de Jong, Aeron C. Hurt, Tadashi Ishida, et al.. 2018. “Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1716197.
- Salvatore, Mirella, Jennifer M. Laplante, Rosemary Soave, Nina Orfali, Markus Plate, Koen Besien, and Kirsten St. George. 2020. “Baloxavir for the Treatment of Influenza in Allogeneic Hematopoietic Stem Cell Transplant Recipients Previously Treated with Oseltamivir”. Transplant Infectious Disease. Wiley. doi:10.1111/tid.13336.
- Taniguchi, Keiichi, Yoshinori Ando, Haruaki Nobori, Shinsuke Toba, Takeshi Noshi, Masanori Kobayashi, Makoto Kawai, et al.. 2019. “Inhibition of Avian-origin Influenza A(H7N9) Virus by the Novel Cap-dependent Endonuclease Inhibitor Baloxavir Marboxil”. Scientific Reports. Springer Science and Business Media LLC. doi:10.1038/s41598-019-39683-4.
- de Jong, M. D., M. G. Ison, A. S. Monto, H. Metev, C. Clark, B. O'Neil, J. Elder, A. McCullough, P. Collis, and W. P. Sheridan. 2014. “Evaluation of Intravenous Peramivir for Treatment of Influenza in Hospitalized Patients”. Clinical Infectious Diseases. Oxford University Press (OUP). doi:10.1093/cid/ciu632.
- Paules, Catharine, and Kanta Subbarao. 2017. “Influenza”. The Lancet. Elsevier BV. doi:10.1016/s0140-6736(17)30129-0.
- Fukao, Keita, Takeshi Noshi, Atsuko Yamamoto, Mitsutaka Kitano, Yoshinori Ando, Takahiro Noda, Kaoru Baba, et al.. 2018. “Combination Treatment with the Cap-dependent Endonuclease Inhibitor Baloxavir Marboxil and a Neuraminidase Inhibitor in a Mouse Model of Influenza A Virus Infection”. Journal of Antimicrobial Chemotherapy. Oxford University Press (OUP). doi:10.1093/jac/dky462.
- Marty, Francisco M, Joan Vidal-Puigserver, Carol Clark, Sandeep K Gupta, Esperanza Merino, Denis Garot, Marianne J Chapman, et al.. 2017. “Intravenous Zanamivir or Oral Oseltamivir for Hospitalised Patients with Influenza: An International, Randomised, Double-blind, Double-dummy, Phase 3 Trial”. The Lancet Respiratory Medicine. Elsevier BV. doi:10.1016/s2213-2600(16)30435-0.
- Rothberg, Michael B., and Sarah D. Haessler. 2010. “Complications of Seasonal and Pandemic Influenza”. Critical Care Medicine. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/ccm.0b013e3181c92eeb.
- De Vlaminck, Iwijn, Lance Martin, Michael Kertesz, Kapil Patel, Mark Kowarsky, Calvin Strehl, Garrett Cohen, et al.. 2015. “Noninvasive Monitoring of Infection and Rejection After Lung Transplantation”. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.1517494112.
- Harper, Scott A., John S. Bradley, Janet A. Englund, Thomas M. File, Stefan Gravenstein, Frederick G. Hayden, Allison J. McGeer, et al.. 2009. “Seasonal Influenza in Adults and Children—diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management: Clinical Practice Guidelines of the Infectious Diseases Society of America”. Clinical Infectious Diseases. Oxford University Press (OUP). doi:10.1086/598513.
- Lee, Nelson, Paul K. S. Chan, David S. C. Hui, Timothy H. Rainer, Eric Wong, Kin‐Wing Choi, Grace C. Y. Lui, et al.. 2009. “Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza”. The Journal of Infectious Diseases. Oxford University Press (OUP). doi:10.1086/600383.
- Burnham, Philip, Kiran Khush, and Iwijn De Vlaminck. 2017. “Myriad Applications of Circulating Cell-free DNA in Precision Organ Transplant Monitoring”. Annals of the American Thoracic Society. American Thoracic Society. doi:10.1513/annalsats.201608-634mg.
- “Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza”. 2011. “Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza”. Annals of Emergency Medicine. Elsevier BV. doi:10.1016/j.annemergmed.2011.07.007.
- Hu, Yunwen, Shuihua Lu, Zhigang Song, Wei Wang, Pei Hao, Jianhua Li, Xiaonan Zhang, et al.. 2013. “Association Between Adverse Clinical Outcome in Human Disease Caused by Novel Influenza A H7N9 Virus and Sustained Viral Shedding and Emergence of Antiviral Resistance”. The Lancet. Elsevier BV. doi:10.1016/s0140-6736(13)61125-3.
- Lee N, Ison MG. Diagnosis, management and outcomes of adults hospitalized with influenza. Antivir Ther. 2012;17(1 Pt B):143-57. doi: 10.3851/IMP2059. Epub 2012 Feb 3.
- Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza. Crit Care Med. 2010 Apr;38(4 Suppl):e91-7. doi: 10.1097/CCM.0b013e3181c92eeb.
- Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, Anovadiya AP, Azziz-Baumgartner E, Baez C, Bassetti M, Beovic B, Bertisch B, Bonmarin I, Booy R, Borja-Aburto VH, Burgmann H, Cao B, Carratala J, Denholm JT, Dominguez SR, Duarte PA, Dubnov-Raz G, Echavarria M, Fanella S, Gao Z, Gerardin P, Giannella M, Gubbels S, Herberg J, Iglesias AL, Hoger PH, Hu X, Islam QT, Jimenez MF, Kandeel A, Keijzers G, Khalili H, Knight M, Kudo K, Kusznierz G, Kuzman I, Kwan AM, Amine IL, Langenegger E, Lankarani KB, Leo YS, Linko R, Liu P, Madanat F, Mayo-Montero E, McGeer A, Memish Z, Metan G, Mickiene A, Mikic D, Mohn KG, Moradi A, Nymadawa P, Oliva ME, Ozkan M, Parekh D, Paul M, Polack FP, Rath BA, Rodriguez AH, Sarrouf EB, Seale AC, Sertogullarindan B, Siqueira MM, Skret-Magierlo J, Stephan F, Talarek E, Tang JW, To KK, Torres A, Torun SH, Tran D, Uyeki TM, Van Zwol A, Vaudry W, Vidmar T, Yokota RT, Zarogoulidis P; PRIDE Consortium Investigators, Nguyen-Van-Tam JS. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014 May;2(5):395-404. doi: 10.1016/S2213-2600(14)70041-4. Epub 2014 Mar 19.
- Paules C, Subbarao K. Influenza. Lancet. 2017 Aug 12;390(10095):697-708. doi: 10.1016/S0140-6736(17)30129-0. Epub 2017 Mar 13.
- 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.
- Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, Anovadiya AP, Azziz-Baumgartner E, Baez C, Bassetti M, Beovic B, Bertisch B, Bonmarin I, Booy R, Borja-Aburto VH, Burgmann H, Cao B, Carratala J, Denholm JT, Dominguez SR, Duarte PA, Dubnov-Raz G, Echavarria M, Fanella S, Gao Z, Gerardin P, Giannella M, Gubbels S, Herberg J, Iglesias AL, Hoger PH, Hu X, Islam QT, Jimenez MF, Kandeel A, Keijzers G, Khalili H, Knight M, Kudo K, Kusznierz G, Kuzman I, Kwan AM, Amine IL, Langenegger E, Lankarani KB, Leo YS, Linko R, Liu P, Madanat F, Mayo-Montero E, McGeer A, Memish Z, Metan G, Mickiene A, Mikic D, Mohn KG, Moradi A, Nymadawa P, Oliva ME, Ozkan M, Parekh D, Paul M, Polack FP, Rath BA, Rodriguez AH, Sarrouf EB, Seale AC, Sertogullarindan B, Siqueira MM, Skret-Magierlo J, Stephan F, Talarek E, Tang JW, To KK, Torres A, Torun SH, Tran D, Uyeki TM, Van Zwol A, Vaudry W, Vidmar T, Yokota RT, Zarogoulidis P; PRIDE Consortium Investigators; Nguyen-Van-Tam JS. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014 May;2(5):395-404. doi: 10.1016/S2213-2600(14)70041-4. Epub 2014 Mar 19.
- 2022. "Baloxavir in Combination With Oseltamivir in Allogenic Bone Marrow Transplant Recipients With Influenza". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT05170009.
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