Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial

• Main Authors: Michele Gerber, Alain P. Rolland, Jennifer A. Chaplin, Mary K. Wloch, Larry R. Smith
• Format: Article
• Language: English
• Published: MDPI AG 2013-09-01
• Series: Vaccines
• Subjects: plasmid DNA vaccine; cytomegalovirus (CMV); glycoprotein B (gB); phosphoprotein 65 (pp65); poloxamer CRL1005; benzalkonium chloride (BAK); hematopoietic cell transplant (HCT); CMV end organ disease (EOD)
• Online Access: http://www.mdpi.com/2076-393X/1/4/398

2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV+) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV+ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.