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

Smith LR, Wloch MK, Chaplin JA, Gerber M, Rolland AP - Vaccines (Basel) (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. lsmith@vical.com.

ABSTRACT
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.

No MeSH data available.


Clinical development timeline of ASP0113 (TransVax) from product concept in 2002 to initiation of a phase 3 trial in 2013. Initiation of various activities is shown in blue diamonds; regulatory activities are shown above the timeline and all others below the timeline. Horizontal blue lines and arrows depict the duration of the indicated activities. Development activities that continued and/or were refined during clinical development are shown in rectangular boxes within the large dotted arrow. Abbreviations: IND, investigational new drug application; FDA, U.S. Food and Drug Administration; EMA, European Medicines Agency; GLP, good laboratory practices; QC, quality control; DS, drug substance.
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vaccines-01-00398-f001: Clinical development timeline of ASP0113 (TransVax) from product concept in 2002 to initiation of a phase 3 trial in 2013. Initiation of various activities is shown in blue diamonds; regulatory activities are shown above the timeline and all others below the timeline. Horizontal blue lines and arrows depict the duration of the indicated activities. Development activities that continued and/or were refined during clinical development are shown in rectangular boxes within the large dotted arrow. Abbreviations: IND, investigational new drug application; FDA, U.S. Food and Drug Administration; EMA, European Medicines Agency; GLP, good laboratory practices; QC, quality control; DS, drug substance.

Mentions: Vical built the capabilities for developing plasmid DNA-based products during development of its lead product, an intralesional immunotherapeutic called Allovectin® (velimogene aliplasmid) [18], which is currently being evaluated in a phase 3 metastatic melanoma trial that is nearing completion. In the early 2000s, product development activities began on several infectious disease targets, the first being CMV; by that time all of the key functional areas were in place to design, create, manufacture, release, and clinically test DNA vaccine product candidates. The functional area expertise included vaccine research, molecular biology, pharmaceutics, nonclinical testing, manufacturing, assay development, quality control (QC), quality assurance, clinical research and operations, regulatory affairs, and project planning and management. As described below, the initial CMV vaccine target indication was for CMV+ HCT recipients. A product development timeline with all supporting activities for this vaccine is displayed in Figure 1 and described in the following sections. The vaccine has been referred to by different names throughout its development history including VCL-CB01, TransVax™, and ASP0113, the current designation of this vaccine since its license to Astellas in 2011.


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

Smith LR, Wloch MK, Chaplin JA, Gerber M, Rolland AP - Vaccines (Basel) (2013)

Clinical development timeline of ASP0113 (TransVax) from product concept in 2002 to initiation of a phase 3 trial in 2013. Initiation of various activities is shown in blue diamonds; regulatory activities are shown above the timeline and all others below the timeline. Horizontal blue lines and arrows depict the duration of the indicated activities. Development activities that continued and/or were refined during clinical development are shown in rectangular boxes within the large dotted arrow. Abbreviations: IND, investigational new drug application; FDA, U.S. Food and Drug Administration; EMA, European Medicines Agency; GLP, good laboratory practices; QC, quality control; DS, drug substance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494211&req=5

vaccines-01-00398-f001: Clinical development timeline of ASP0113 (TransVax) from product concept in 2002 to initiation of a phase 3 trial in 2013. Initiation of various activities is shown in blue diamonds; regulatory activities are shown above the timeline and all others below the timeline. Horizontal blue lines and arrows depict the duration of the indicated activities. Development activities that continued and/or were refined during clinical development are shown in rectangular boxes within the large dotted arrow. Abbreviations: IND, investigational new drug application; FDA, U.S. Food and Drug Administration; EMA, European Medicines Agency; GLP, good laboratory practices; QC, quality control; DS, drug substance.
Mentions: Vical built the capabilities for developing plasmid DNA-based products during development of its lead product, an intralesional immunotherapeutic called Allovectin® (velimogene aliplasmid) [18], which is currently being evaluated in a phase 3 metastatic melanoma trial that is nearing completion. In the early 2000s, product development activities began on several infectious disease targets, the first being CMV; by that time all of the key functional areas were in place to design, create, manufacture, release, and clinically test DNA vaccine product candidates. The functional area expertise included vaccine research, molecular biology, pharmaceutics, nonclinical testing, manufacturing, assay development, quality control (QC), quality assurance, clinical research and operations, regulatory affairs, and project planning and management. As described below, the initial CMV vaccine target indication was for CMV+ HCT recipients. A product development timeline with all supporting activities for this vaccine is displayed in Figure 1 and described in the following sections. The vaccine has been referred to by different names throughout its development history including VCL-CB01, TransVax™, and ASP0113, the current designation of this vaccine since its license to Astellas in 2011.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA. lsmith@vical.com.

ABSTRACT
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.

No MeSH data available.