Abstract
BackgroundCytomegalovirus (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.MethodsIn 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).FindingsPatients 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).InterpretationASP0113 did not reduce overall mortality or CMV EOD by 1 year post-transplant. Safety findings were similar between groups.FundingAstellas Pharma Global Development, Inc .
Highlights
Immunocompromised patients, including patients undergoing allogeneic haematopoietic cell transplantation, are vulnerable to cytomegalovirus (CMV) infection or reactivation [1]
Letermovir seemed to be associated with decreased all-cause mortality at week 24; late CMV reactivation occurred after discontinuation of letermovir, indicating a need for novel strategies to stimulate anti-CMV immunity. [6]
This study demonstrated a significantly decreased duration of viraemia (p = 0.048) and reduced number of days of ganciclovir treatment (p = 0.0287) in CMV-seronegative recipients [10]
Summary
Immunocompromised patients, including patients undergoing allogeneic haematopoietic cell transplantation (alloHCT), are vulnerable to cytomegalovirus (CMV) infection or reactivation [1]. Treatment with ganciclovir or valganciclovir is associated with myelosuppression, as well as bacterial and fungal infections [3À5] In view of these toxicities, the riskÀbenefit of administering potentially toxic agents as a prophylactic or pre-emptive treatment to patients who may be at low risk of developing. In a phase 3, doubleblind, placebo-controlled study, letermovir significantly reduced the number of patients with clinically significant CMV infection by week 24 post-transplant (p
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