Pharmacokinetics and Immunogenicity of ASP0113 in CMV ‐Seronegative Dialysis Patients and CMV‐Seronegative and ‐Seropositive Healthy Subjects

AbstractCytomegalovirus (CMV) infection causes significant morbidity and mortality in immunocompromised transplant patients. ASP0113, a first ‐in‐class DNA vaccine containing plasmids encoding CMV phosphoprotein 65 and glycoprotein B (gB), was evaluated in a phase 1b, subject‐blinded study in CMV‐seropositive (n = 13) and CMV‐seronegative (n = 12) healthy and CMV‐seronegative dialysis subjects (n = 12) randomized to ASP0 113 or placebo. End points included pharmacokinetics, anti‐gB antibody levels, phosphoprotein 65–specific T‐cell responses measured by ex vivo enzyme‐linked immune absorbent spot (ELISpot) assay and 10‐day cultured ELISpot and Stat T‐cell activation assays, and safety. ASP0113 concentrat ions peaked at 2‐10 and 24‐48 hours; the pharmacokinetics were similar across groups. No group demonstrated significant anti‐gB antibody responses. T‐cell responder rates in the cultured ELISpot assay were 8/12 (66.7%, 95%CI 35% to 90%) and 4/12 (33.3%, 95%CI 10% to 65%) in CMV‐seronegativ e healthy subjects and dialysis patients, respectively, whereas ex vivo ELISpot assay response rates were 4/11 (36.4%, 95%CI 11% to 69%) and 0/12, respectively. Responses peaked at week 27, with lower magnitude observed in CMV‐seronegative dialysis patients versus CMV‐seronegative healthy subjec ts. No serious adverse events occurred; the most common adverse event in ASP0113‐vaccinated patients was injection‐site pain (64.9%). Some CMV‐seron...

Source: Clinical Pharmacology in Drug Development - March 31, 2020 Category: Drugs & Pharmacology Authors: Peter L. Bonate, Charles Van Sant, Kathy Cho, Erin C. Zook, Larry R. Smith, Sou Boutsaboualoy, Ming Ye, Xuegong Wang, Ruishan Wu, Anne Koester, Diane Rammelsberg, Ronald Goldwater, Thomas C. Marbury Tags: Original Manuscript Source Type: research