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

Cytomegalovirus (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‐seropositiv...

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Published in:Clinical pharmacology in drug development 2020-05, Vol.9 (4), p.444-455
Main Authors: Bonate, Peter L., Van Sant, Charles, Cho, Kathy, Zook, Erin C., Smith, Larry R., Boutsaboualoy, Sou, Ye, Ming, Wang, Xuegong, Wu, Ruishan, Koester, Anne, Rammelsberg, Diane, Goldwater, Ronald, Marbury, Thomas C.
Format: Article
Language:English
Subjects:
ASP0113
Cytomegalovirus
Cytomegalovirus Infections - chemically induced
Cytomegalovirus Infections - prevention & control
DNA vaccine
Healthy Volunteers
Hemodialysis
Humans
immunogenicity
Pharmacokinetics
pharmacokinetics/pharmacodynamics
Pharmacology
Phosphoproteins
Renal Dialysis
T cell receptors
Vaccines, DNA - adverse effects
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Summary:Cytomegalovirus (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 ASP0113 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 concentrations 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‐seronegative 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 subjects. No serious adverse events occurred; the most common adverse event in ASP0113‐vaccinated patients was injection‐site pain (64.9%). Some CMV‐seronegative healthy subjects and dialysis patients had T‐cell responses; no humoral responses were detected.
ISSN:2160-763X
2160-7648
DOI:10.1002/cpdd.792