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Maribavir for Refractory or Resistant Cytomegalovirus Infections in Hematopoietic-cell or Solid-organ Transplant Recipients: A Randomized, Dose-ranging, Double-blind, Phase 2 Study.
- Source :
-
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2019 Apr 08; Vol. 68 (8), pp. 1255-1264. - Publication Year :
- 2019
-
Abstract
- Background: Cytomegalovirus (CMV) infections that are refractory or resistant (RR) to available antivirals ([val]ganciclovir, foscarnet, cidofovir) are associated with higher mortality in transplant patients. Maribavir is active against RR CMV strains.<br />Methods: Hematopoietic-cell or solid-organ transplant recipients ≥12 years old with RR CMV infections and plasma CMV deoxyribonucleic acid (DNA) ≥1000 copies/mL were randomized (1:1:1) to twice-daily dose-blinded maribavir 400, 800, or 1200 mg for up to 24 weeks. The primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment. Safety analyses included the frequency and severity of treatment-emergent adverse events (TEAEs).<br />Results: From July 2012 to December 2014, 120 patients were randomized and treated (40 per dose group): 80/120 (67%) patients achieved undetectable CMV DNA within 6 weeks of treatment (95% confidence interval, 57-75%), with rates of 70%, 63%, and 68%, respectively, for maribavir 400, 800, and 1200 mg twice daily. Recurrent on-treatment CMV infections occurred in 25 patients; 13 developed mutations conferring maribavir resistance. Maribavir was discontinued due to adverse events in 41/120 (34%) patients, and 17/41 discontinued due to CMV infections. During the study, 32 (27%) patients died, 4 due to CMV disease. Dysgeusia was the most common TEAE (78/120; 65%) and led to maribavir discontinuation in 1 patient. Absolute neutrophil counts <1000/µL were noted in 12/106 (11%) evaluable patients, with rates similar across doses.<br />Conclusions: Maribavir ≥400 mg twice daily was active against RR CMV infections in transplant recipients; no new safety signals were identified.<br />Clinical Trials Registration: NCT01611974.<br /> (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Subjects :
- Adolescent
Adult
Dose-Response Relationship, Drug
Double-Blind Method
Drug Resistance, Viral
Female
Hematopoietic Stem Cell Transplantation
Humans
Male
Transplant Recipients
Young Adult
Antiviral Agents administration & dosage
Benzimidazoles administration & dosage
Cytomegalovirus Infections drug therapy
Immunocompromised Host
Ribonucleosides administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6591
- Volume :
- 68
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Publication Type :
- Academic Journal
- Accession number :
- 30329038
- Full Text :
- https://doi.org/10.1093/cid/ciy706