A randomised, placebo-controlled phase 3 study to evaluate the efficacy and safety of ASP0113, a DNA-based CMV vaccine, in seropositive allogeneic haematopoietic cell transplant recipients
Ljungman, Per (Karolinska Institutet (Estocolm, Suècia))
Bermúdez, Arancha (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Logan, Aaron C. (Division of Hematology and Blood and Marrow Transplantation. Department of Medicine. University of California)
Kharfan-Dabaja, Mohamed A. (Department of Blood and Marrow Transplantation. H. Lee Moffitt Cancer Center and Research Institute and University of South Florida)
Chevallier, Patrice (Service d'Hématologie Clinique. CHU de Nantes. 44093. Nantes. France and CRCINA / INSERM UMR1232 / CNRS ERL6001 IRS UN - 8)
Martino Bofarull, Rodrigo (Institut d'Investigació Biomèdica Sant Pau)
Wulf, Gerald (Department of Hematology and Medical Oncology. University Medical Center Göttingen)
Selleslag, Dominik (Department of Hematology. AZ Sint-Jan Brugge-Oostende)
Kakihana, Kazuhiko (Hematology Division. Tokyo Metropolitan Komagome Hospital)
Langston, Amelia (Winship Cancer Institute. Emory University)
Lee, Dong-Gun. (Catholic University of Korea)
Solano, Carlos (Instituto de Investigación Sanitaria INCLIVA (València, Comunitat Valenciana))
Okamoto, Shinichiro (Division of Hematology. Department of Medicine. Kelo University School of Medicine)
Smith, Larry R. (Vical)
Boeckh, Michael (Vaccine and Infectious Disease Division. Fred Hutchinson Cancer Research Center and University of Washington)
Wingard, John Reid (Division of Hematology & Oncology. Department of Medicine. University of Florida)
Cywin, Beth (Astellas Pharma Global Development)
Fredericks, Christine (Astellas Pharma Global Development)
Lademacher, Christopher (Astellas Pharma Global Development)
Wang, Xuegong (Astellas Pharma Global Development)
Young, James (Astellas Pharma Global Development)
Maertens, Johan (K.U. Leuven and Department of Hematology)

Date:	2021
Abstract:	Background: Cytomegalovirus (CMV) is a complication of allogeneic haematopoietic cell transplantation (allo-HCT). ASP0113, a DNA-based vaccine, contains two plasmids encoding human CMV glycoprotein B and phosphoprotein 65 (pp65). We assessed ASP0113 in CMV-seropositive allo-HCT recipients. Methods: In this phase 3, randomised, placebo-controlled study, CMV-seropositive allo-HCT recipients were randomly assigned (1:1) via interactive response technology to receive five injections of 1 mL of 5 mg/mL ASP0113 or placebo. The pharmacist and designated staff were unblinded. Masked syringes maintained the blind for patients and study personnel. Efficacy and safety analyses included patients who received ≥1 dose of ASP0113/placebo. The primary efficacy endpoint was the proportion of allo-HCT recipients with composite all-cause mortality and adjudicated CMV end-organ disease (EOD) by 1 year post-transplant. ClinicalTrials. gov: NCT01877655 (not recruiting). Findings: Patients were recruited between Sept 11, 2013 and Sept 21, 2016. Overall, 501 patients received ≥1 dose of ASP0113 (n = 246) or placebo (n = 255). The proportion of patients with composite all-cause mortality and adjudicated CMV EOD by 1 year post-transplant was 35. 4% (n = 87) with ASP0113 and 30•2% (n = 77) with placebo (odds ratio 1. 27; 95% confidence interval: 0. 87 to 1. 85; p = 0. 205). Incidence of injection site-related treatment-emergent adverse events (TEAEs) was higher with ASP0113 than placebo. Overall incidence and severity of other TEAEs was similar between groups. T-cell response to pp65 increased over time and was greater with placebo than ASP0113 (p = 0. 027). Interpretation: ASP0113 did not reduce overall mortality or CMV EOD by 1 year post-transplant. Safety findings were similar between groups. Funding: Astellas Pharma Global Development, Inc.
Note:	Altres ajuts: Astellas Pharma Global Development, Inc.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	EClinicalMedicine, Vol. 33 (march 2021) , p. 100787, ISSN 2589-5370

DOI: 10.1016/j.eclinm.2021.100787
PMID: 33842870

11 p, 1.2 MB

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