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

Per Ljungman (1, 2) , Arancha Bermudez (3) , Aaron C Logan (4) , Mohamed A Kharfan-Dabaja (5) , Patrice Chevallier (6) , Rodrigo Martino (7) , Gerald Wulf (8) , Dominik Selleslag (9) , Kazuhiko Kakihana (10) , Amelia Langston (11) , Dong-Gun Lee (12) , Carlos Solano (13) , Shinichiro Okamoto (14) , Larry R Smith (15) , Michael Boeckh (16, 17) , John R Wingard (18) , Beth Cywin (19) , Christine Fredericks (19) , Christopher Lademacher (19) , Xuegong Wang (19) , James Young (19) , Johan Maertens (20)

1 Karolinska University Hospital [Stockholm]
2 Karolinska Institutet [Stockholm]
3 Hospital Universitario Marqués de Valdecilla [Santander]
4 UC San Francisco - University of California [San Francisco]
5 USF - University of South Florida [Tampa]
6 CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications
7 Hospital de la Santa Creu i Sant Pau
8 UMG - University Medical Center Göttingen
9 AZ Sint-Jan
10 TMU - Tokyo Metropolitan University [Tokyo]
11 Emory University [Atlanta, GA]
12 Catholic University of Korea
13 UV - Universitat de València
14 Keio University School of Medicine [Tokyo, Japan]
15 Vical Inc. [San Diego, CA, USA]
16 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
17 University of Washington [Seattle]
18 UF - University of Florida [Gainesville]
19 Astellas Pharma Global Development, Inc. [Northbrook, IL, USA]
20 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven

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.

Domaines: Cancer

Per Ljungman, Arancha Bermudez, Aaron C Logan, Mohamed A Kharfan-Dabaja, Patrice Chevallier, et al.. 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. EClinicalMedicine, 2021, 33, pp.100787. ⟨10.1016/j.eclinm.2021.100787⟩. ⟨inserm-03532634⟩