Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial.
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.
Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. lsmith@vical.com.
Larry R
LR
Smith
Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. mwloch@vical.com.
Mary K
MK
Wloch
Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. jchaplin@vical.com.
Jennifer A
JA
Chaplin
Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL 60062, USA. michele.gerber@astellas.com.
Michele
M
Gerber
Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. arolland@vical.com.
Alain P
AP
Rolland
CMV end organ disease (EOD); benzalkonium chloride (BAK); cytomegalovirus (CMV); glycoprotein B (gB); hematopoietic cell transplant (HCT); phosphoprotein 65 (pp65); plasmid DNA vaccine; poloxamer CRL1005