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.

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 (

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 .

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

Dr Ljungman reports grants, personal fees and non-financial support from 10.13039/501100004948Astellas personal fees from Vical, during the conduct of the study; personal fees from AiCuris, grants from Merck, grants from Shire, outside the submitted work. Dr Bermudez reports other from Astellas, during the conduct of the study. Dr Logan reports other from Astellas, during the conduct of the study; other from Novartis, outside the submitted work. Dr Kharfan-Dabaja reports other from Seattle Genetics, other from Alexion Pharmaceuticals, other from Incyte, personal fees from Daiichi Sankyo, personal fees from Pharmacyclics, outside the submitted work. Dr Chevallier has nothing to disclose. Dr Martino reports other from Astellas, during the conduct of the study. Dr Wulf reports personal fees from Astellas, during the conduct of the study. Dr Selleslag reports personal fees from Astellas Pharma Global Development, Inc., personal fees from GlaxoSmithKline, personal fees from MSD, personal fees from Pfizer, during the conduct of the study. Dr Kakihana reports personal fees from Chugai Pharmaceutical Co. Ltd, personal fees from Kyowa Hakko Kirin, personal fees from Bristol-Myers Squibb, personal fees from Takeda Pharmaceutical Co., personal fees from Dainippon Sumitomo Pharma, outside the submitted work. Dr Langston has nothing to disclose. Dr Lee reports grants from Astellas, during the conduct of the study; grants from GSK, personal fees from MSD, personal fees from Pfizer, personal fees from Gilead, personal fees from SL Vaxigen, outside the submitted work. Dr Solano reports grants from Astellas Pharma Global Development, Inc., during the conduct of the study; personal fees from Gilead, personal fees from Mitsubishi Tanabe Pharma, outside the submitted work. Dr Okamoto reports grants, personal fees and other from Astellas Pharma, during the conduct of the study. Dr Smith reports personal fees from Astellas Pharma, during the conduct of the study. Dr Boeckh reports grants from Astellas Pharma Global Development Inc, during the conduct of the study; grants and personal fees from Gilead, grants and personal fees from Merck, grants and personal fees from Takeda, grants and personal fees from Vir Bio, personal fees from Allovir, personal fees from GlaxoSmithKline, personal fees from Moderna, personal fees from Oxford Immunotec, personal fees from Evrys Bio, personal fees from Helocyte, grants from Lophius Biosciences, outside the submitted work. Dr Wingard reports personal fees from Astellas Pharma Global Development, Inc., during the conduct of the study; personal fees from Allovir, personal fees from Ansun, personal fees from Celgene, personal fees from Cidara, personal fees from Merck, personal fees from Pluristem, personal fees from Shire, outside the submitted work. Dr Cywin reports personal fees from Astellas, during the conduct of the study, and is an employee of Astellas. Dr Fredericks reports personal fees from Astellas, during the conduct of the study; personal fees from Astellas, outside the submitted work; and is an employee of Astellas. Dr Lademacher reports personal fees from Astellas, during the conduct of the study, and is an employee of Astellas. Dr Wang reports other from Astellas, during the conduct of the study; other from Astellas Pharma global Development, outside the submitted work; and employment by Astellas. Dr Young reports personal fees from Astellas, during the conduct of the study, and is an employee of Astellas. Dr Maertens reports personal fees and non-financial support from 10.13039/501100004948Astellas, grants, personal fees and non-financial support from 10.13039/100004334Merck, personal fees and non-financial support from 10.13039/100004319Pfizer, personal fees and non-financial support from Basilea, personal fees and non-financial support from F2G, personal fees and non-financial support from 10.13039/100010643Cidara, grants, personal fees and non-financial support from 10.13039/100005564Gilead, outside the submitted work.