Safety of ASP0113, a cytomegalovirus DNA vaccine, in recipients undergoing allogeneic hematopoietic cell transplantation: an open-label phase 2 trial

Abstract

Cytomegalovirus (CMV) infection/reactivation is a serious complication after hematopoietic cell transplantation (HCT). The DNA vaccine ASP0113 contains two plasmids encoding CMV antigens (glycoprotein B and tegument phosphoprotein 65) that stimulate humoral and cellular immunity. Between June 2013 and February 2014, Astellas conducted a phase 2, open-label, uncontrolled, three-center trial to investigate the safety and tolerability of ASP0113 in Japanese patients undergoing HCT for hematologic disorders. Ten patients aged 22-61 years were enrolled; nine received at least one dose of ASP0113. Six patients received all five doses of ASP0113 5 mg at intervals before and after HCT. Pre-emptive antiviral therapy was allowed. One patient died following relapse of primary disease. All patients had serious adverse events deemed unrelated to ASP0113. CMV viremia (assessed by CMV antigenemia) occurred in seven patients, who then received anti-CMV therapy. No patients developed CMV end-organ disease. Adverse events associated with ASP0113 injection included pyrexia (three patients), skin reactions [injection site pain, injection site tenderness, and erythema (two patients each); and rash, injection site erythema, injection site induration, and injection site swelling (one patient each)], and hyperuricemia (one patient). ASP0113 was well tolerated in Japanese HCT recipients. Further studies should evaluate its efficacy and safety. ClinicalTrials.gov Identifier: NCT01903928.

Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy

“…CMV pp65/gB plasmid vaccine ASP0113 containing both pp65‐ and gB‐encoded DNA plasmids was developed to control the reactivation of latent CMV or the prevention of virus introduction via donor tissues in transplant patients. Once encoded proteins were expressed, they could induce the immune system against CMV‐positive cells . A phase III clinical trial study to evaluate the efficacy of ASP0113 was initiated by Astellas Pharma Global Development in 2013 and CMV‐seropositive patients with allogeneic, hematopoietic cell transplant were recruited.…”

“…Once encoded proteins were expressed, they could induce the immune system against CMV-positive cells. 100…”

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

“…NCT00285259͒ demonstrated an acceptable safety profile and a statistically significant reduction of CMV viremia following vaccination, as well as a trend toward reduced use of anti-CMV antivirals in immunized subjects (74). Safety was further evaluated in an open-label, uncontrolled phase II study (75). A phase III clinical trial was recently initiated to continue the evaluation of ASP0113 efficacy in HSCT patients ͑http://www.clinicaltrials .gov registration no.…”

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

“…Several multi-component subunit (217), recombinant live-attenuated (218), and DNA (219) vaccine candidates aimed at achieving broad cross-neutralizing humoral and cellular immune responses are currently under investigation. One clear caveat for the CMV vaccine strategy to be effective is the need for its administration at a young age, and the ability for the vaccine to impart long-lasting immunity.…”