Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial : A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America..
BACKGROUND: Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir.
METHODS: In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up. The primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). The key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8 through week 16. Treatment-emergent adverse events (TEAEs) were assessed.
RESULTS: Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of noninferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference: -7.7%; 95% confidence interval [CI]: -14.98, -.36; lower limit of 95% CI of treatment difference exceeded -7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference: 4.4%; 95% CI: -3.91, 12.76). With maribavir (vs valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%).
CONCLUSIONS: Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia. Clinical Trials Registration. NCT02927067 [AURORA].
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 78(2024), 3 vom: 20. März, Seite 562-572 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Papanicolaou, Genovefa A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 02.04.2024 published: Print ClinicalTrials.gov: NCT02927067 Citation Status MEDLINE |
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| doi: |
10.1093/cid/ciad709 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Papanicolaou, Genovefa A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial |b A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir |
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| 500 | |a Date Completed 22.03.2024 | ||
| 500 | |a Date Revised 02.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02927067 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. | ||
| 520 | |a BACKGROUND: Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir | ||
| 520 | |a METHODS: In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up. The primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). The key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8 through week 16. Treatment-emergent adverse events (TEAEs) were assessed | ||
| 520 | |a RESULTS: Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of noninferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference: -7.7%; 95% confidence interval [CI]: -14.98, -.36; lower limit of 95% CI of treatment difference exceeded -7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference: 4.4%; 95% CI: -3.91, 12.76). With maribavir (vs valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%) | ||
| 520 | |a CONCLUSIONS: Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia. Clinical Trials Registration. NCT02927067 [AURORA] | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cytomegalovirus | |
| 650 | 4 | |a hematopoietic cell transplant | |
| 650 | 4 | |a maribavir | |
| 650 | 4 | |a valganciclovir | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Dichlororibofuranosylbenzimidazole |2 NLM | |
| 650 | 7 | |a 53-85-0 |2 NLM | |
| 650 | 7 | |a maribavir |2 NLM | |
| 650 | 7 | |a PTB4X93HE1 |2 NLM | |
| 650 | 7 | |a Valganciclovir |2 NLM | |
| 650 | 7 | |a GCU97FKN3R |2 NLM | |
| 700 | 1 | |a Avery, Robin K |e verfasserin |4 aut | |
| 700 | 1 | |a Cordonnier, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Duarte, Rafael F |e verfasserin |4 aut | |
| 700 | 1 | |a Haider, Shariq |e verfasserin |4 aut | |
| 700 | 1 | |a Maertens, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Peggs, Karl S |e verfasserin |4 aut | |
| 700 | 1 | |a Solano, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Jo-Anne H |e verfasserin |4 aut | |
| 700 | 1 | |a Fournier, Martha |e verfasserin |4 aut | |
| 700 | 1 | |a Murray, Rose Ann |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Winston, Drew J |e verfasserin |4 aut | |
| 700 | 0 | |a AURORA Trial Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Singhal, Deepak |e investigator |4 oth | |
| 700 | 1 | |a Sasadeusz, Joe |e investigator |4 oth | |
| 700 | 1 | |a Maertans, Johan |e investigator |4 oth | |
| 700 | 1 | |a Georgala, Aspasia |e investigator |4 oth | |
| 700 | 1 | |a Selleslag, Dominik |e investigator |4 oth | |
| 700 | 1 | |a Verlinden, Anke |e investigator |4 oth | |
| 700 | 1 | |a Kerre, Tessa |e investigator |4 oth | |
| 700 | 1 | |a De Becker, Ann |e investigator |4 oth | |
| 700 | 1 | |a Haider, Shariq |e investigator |4 oth | |
| 700 | 1 | |a Wright, Alissa |e investigator |4 oth | |
| 700 | 1 | |a Wu, Depei |e investigator |4 oth | |
| 700 | 1 | |a Vrhovac, Radovan |e investigator |4 oth | |
| 700 | 1 | |a Cordonnier, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Berceanu, Ana |e investigator |4 oth | |
| 700 | 1 | |a Francois, Sylvie |e investigator |4 oth | |
| 700 | 1 | |a Michonneau, David |e investigator |4 oth | |
| 700 | 1 | |a Huynh, Anne |e investigator |4 oth | |
| 700 | 1 | |a Bethge, Wolfgang |e investigator |4 oth | |
| 700 | 1 | |a Kaufmann, Martin |e investigator |4 oth | |
| 700 | 1 | |a Stelljes, Matthias |e investigator |4 oth | |
| 700 | 1 | |a Franke, Georg-Nikolaus |e investigator |4 oth | |
| 700 | 1 | |a Schmitt, Timo |e investigator |4 oth | |
| 700 | 1 | |a Müller, Lutz |e investigator |4 oth | |
| 700 | 1 | |a Ahlgrimm, Manfred |e investigator |4 oth | |
| 700 | 1 | |a Niederland, Judith |e investigator |4 oth | |
| 700 | 1 | |a Tsirigotis, Panagiotis |e investigator |4 oth | |
| 700 | 1 | |a Ram, Ron |e investigator |4 oth | |
| 700 | 1 | |a Shemtov, Noga |e investigator |4 oth | |
| 700 | 1 | |a Rosenvald-Zuckerman, Tsila |e investigator |4 oth | |
| 700 | 1 | |a Cutini, Ilaria |e investigator |4 oth | |
| 700 | 1 | |a Busca, Alessandro |e investigator |4 oth | |
| 700 | 1 | |a Onida, Francesco |e investigator |4 oth | |
| 700 | 1 | |a Tecchio, Cristina |e investigator |4 oth | |
| 700 | 1 | |a Browett, Peter |e investigator |4 oth | |
| 700 | 1 | |a Do, Young Rok |e investigator |4 oth | |
| 700 | 1 | |a Kim, Sung Hyun |e investigator |4 oth | |
| 700 | 1 | |a Ho, Aloysius |e investigator |4 oth | |
| 700 | 1 | |a Koh, Liang Piu |e investigator |4 oth | |
| 700 | 1 | |a Lopez, Maria Lourdes Vazquez |e investigator |4 oth | |
| 700 | 1 | |a Jimenez, Javier Lopez |e investigator |4 oth | |
| 700 | 1 | |a Coll, Christelle Ferra |e investigator |4 oth | |
| 700 | 1 | |a De la Camara, Rafael |e investigator |4 oth | |
| 700 | 1 | |a Solano, Carlos |e investigator |4 oth | |
| 700 | 1 | |a Mussetti, Alberto |e investigator |4 oth | |
| 700 | 1 | |a Llamas, Juan Carlos Vallejo |e investigator |4 oth | |
| 700 | 1 | |a Suñol, Pere Barba |e investigator |4 oth | |
| 700 | 1 | |a Chacón, Manuel Jurado |e investigator |4 oth | |
| 700 | 1 | |a Duarte, Rafael F |e investigator |4 oth | |
| 700 | 1 | |a Rodríguez, María Aranzazu Bermúdez |e investigator |4 oth | |
| 700 | 1 | |a Mueller, Nicolas |e investigator |4 oth | |
| 700 | 1 | |a Ozdogu, Hakan |e investigator |4 oth | |
| 700 | 1 | |a Gurman, Gunhan |e investigator |4 oth | |
| 700 | 1 | |a Bloor, Adrian |e investigator |4 oth | |
| 700 | 1 | |a Kishore, Bhuvan |e investigator |4 oth | |
| 700 | 1 | |a Peggs, Kari S |e investigator |4 oth | |
| 700 | 1 | |a Milojkovic, Dragana |e investigator |4 oth | |
| 700 | 1 | |a Orchard, Kim |e investigator |4 oth | |
| 700 | 1 | |a Toth, Arpad Gabor |e investigator |4 oth | |
| 700 | 1 | |a Koh, Mickey |e investigator |4 oth | |
| 700 | 1 | |a Avery, Robin K |e investigator |4 oth | |
| 700 | 1 | |a Pisano, Jennifer |e investigator |4 oth | |
| 700 | 1 | |a Alangaden, George |e investigator |4 oth | |
| 700 | 1 | |a Winston, Drew J |e investigator |4 oth | |
| 700 | 1 | |a Papanicolau, Genovefa |e investigator |4 oth | |
| 700 | 1 | |a Gewurz, Benjamin |e investigator |4 oth | |
| 700 | 1 | |a Marty, Francisco M |e investigator |4 oth | |
| 700 | 1 | |a Young, Jo-Anne H |e investigator |4 oth | |
| 700 | 1 | |a Hagen, Patrick |e investigator |4 oth | |
| 700 | 1 | |a Reshef, Ran |e investigator |4 oth | |
| 700 | 1 | |a Abedin, Sameem |e investigator |4 oth | |
| 700 | 1 | |a Shaughnessy, Paul |e investigator |4 oth | |
| 700 | 1 | |a Gibson, Laura |e investigator |4 oth | |
| 700 | 1 | |a Shore, Joan Tsiporah |e investigator |4 oth | |
| 700 | 1 | |a Bachier, Carlos R |e investigator |4 oth | |
| 700 | 1 | |a Yared, Jean |e investigator |4 oth | |
| 700 | 1 | |a Malinis, Maricar |e investigator |4 oth | |
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