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Month 30 & 42 Extension Studies of CRD-004 Primary Study

Primary Purpose

Herpes Zoster

Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Blood sampling for assay of persistence of immunogenicity
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Herpes Zoster focused on measuring GSK Biologicals, Varicella Zoster Virus (VZV), Intracellular cytokine staining (ICS), Vaccine, Cell mediated immunity (CMI), Herpes Zoster (HZ), Shingles

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study;
  • Subjects who successfully completed the primary study and who did not receive Varilrix in the primary study;
  • Written informed consent obtained from the subject;
  • Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) within 1 month preceding the study start, or planned use during the study period;
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first study procedure, including corticosteroids, except inhaled and topical steroids are allowed;
  • Administration or planned administration of a vaccine not foreseen by the study protocol within 2 weeks before the first study procedure, with the exception of the Influenza vaccine, which can be administered 1 week preceding the first study procedure;
  • Previous vaccination against HZ, except the study vaccine administered in the primary study;
  • History of HZ (shingles);
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination;
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the first study procedure or planned administration during the study period.

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

GSK1437173A 18-30 Years Old Group

GSK1437173A 50-70 Years Old Group

Arm Description

Subjects aged 18 to 30 years old receiving 2 doses GSK1437173A vaccine in the primary study.

Subjects aged 50 to 70 years old receiving 2 doses GSK1437173A vaccine in the primary study.

Outcomes

Primary Outcome Measures

Frequencies of Glycoprotein E (gE)-Specific Cluster of Differentiation 4 (CD4) / CD8 T Cells With at Least Two Antigen-specific Cytokines: Interferon Gamma (IFN-γ), Interleukin 2 (IL-2), Tumor Necrosis Factor Alpha (TNF-α), CD 40 Ligand (CD40L).
The analysis focused on those gE-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, and CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE was performed, since no long-term vaccine effect on gE-specific CD8 T cell response was detected.
Frequencies of Varicella Zoster Virus (VZV)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L).
The analysis focused on those VZV-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to VZV was performed, since no long-term vaccine effect on VZV-specific CD8 T cell response was detected.
Frequencies of Glycoprotein E (gE)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L).
The analysis focused on those gE-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE was performed, since no long-term vaccine effect on gE-specific CD8 T cell response was detected.
Frequencies of Varicella Zoster Virus (VZV)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L).
The analysis focused on those VZV-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to VZV was performed, since no long-term vaccine effect on VZV-specific CD8 T cell response was detected.

Secondary Outcome Measures

Frequencies of gE- and VZV-specific CD4/CD8 T Cells With Antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L Secretion/Expression.
The analysis focused on those gE- and VZV-specific CD4 T cells secreting any cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE or VZV was performed, since no long-term vaccine effect on gE- and VZV-specific CD8 T cell response was detected.
Anti-gE Antibody (Ab) Concentrations
As determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and expressed as ELISA units per milliliter (EL.U/mL).
Anti-VZV Ab Concentrations
As determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and expressed as ELISA units per milliliter (EL.U/mL).
Frequencies of gE-specific Memory B Cells
As determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay.
Frequencies of VZV-specific Memory B Cells
As determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay.
Number of Subjects With Any Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects With Clinically Diagnosed Herpes Zoster (HZ) Episodes
This assay tabulated the number of subjects with clinically diagnosed HZ episodes, defined as any cutaneous HZ-like rash.

Full Information

First Posted
June 26, 2007
Last Updated
June 11, 2019
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00492648
Brief Title
Month 30 & 42 Extension Studies of CRD-004 Primary Study
Official Title
An Extension Study to Evaluate the Persistence of the Immune Responses Induced by GSK Biologicals Zoster Vaccine, GSK324332A, Administered in Healthy Adult Subjects Aged 18-30 Years and 50-70 Years
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
June 25, 2007 (Actual)
Primary Completion Date
June 23, 2008 (Actual)
Study Completion Date
June 23, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

5. Study Description

Brief Summary
The safety and immunogenicity of the GSK324332A vaccine has been evaluated up to Month 12 post-vaccination in the primary study. In the extension studies presented here, the persistence of the cellular and humoral immune responses will be evaluated 30 and 42 months after the first vaccination in young and elderly adults who received the GSK324332A vaccine. This protocol posting deals only with objectives & outcome measures of the extension phase at Months 30 and 42. No new recruitment will be done in these extension phases of the primary study. No vaccines are administered in this phase of the study.
Detailed Description
All subjects in these extension phases of the study were previously vaccinated with the investigational herpes zoster vaccine GSK1437173A. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. Further details on the primary study can be found on our GSK study register (https://www.gsk-studyregister.com/advanced-search) by searching on the GSK study identifier 101501.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Herpes Zoster
Keywords
GSK Biologicals, Varicella Zoster Virus (VZV), Intracellular cytokine staining (ICS), Vaccine, Cell mediated immunity (CMI), Herpes Zoster (HZ), Shingles

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GSK1437173A 18-30 Years Old Group
Arm Type
Experimental
Arm Description
Subjects aged 18 to 30 years old receiving 2 doses GSK1437173A vaccine in the primary study.
Arm Title
GSK1437173A 50-70 Years Old Group
Arm Type
Experimental
Arm Description
Subjects aged 50 to 70 years old receiving 2 doses GSK1437173A vaccine in the primary study.
Intervention Type
Procedure
Intervention Name(s)
Blood sampling for assay of persistence of immunogenicity
Intervention Description
Two blood samples: 30 and 42 months after first vaccination
Primary Outcome Measure Information:
Title
Frequencies of Glycoprotein E (gE)-Specific Cluster of Differentiation 4 (CD4) / CD8 T Cells With at Least Two Antigen-specific Cytokines: Interferon Gamma (IFN-γ), Interleukin 2 (IL-2), Tumor Necrosis Factor Alpha (TNF-α), CD 40 Ligand (CD40L).
Description
The analysis focused on those gE-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, and CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE was performed, since no long-term vaccine effect on gE-specific CD8 T cell response was detected.
Time Frame
At Month 30 after the first vaccination.
Title
Frequencies of Varicella Zoster Virus (VZV)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L).
Description
The analysis focused on those VZV-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to VZV was performed, since no long-term vaccine effect on VZV-specific CD8 T cell response was detected.
Time Frame
At Month 30 after the first vaccination
Title
Frequencies of Glycoprotein E (gE)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L).
Description
The analysis focused on those gE-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE was performed, since no long-term vaccine effect on gE-specific CD8 T cell response was detected.
Time Frame
At Month 42 after the first vaccination
Title
Frequencies of Varicella Zoster Virus (VZV)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L).
Description
The analysis focused on those VZV-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to VZV was performed, since no long-term vaccine effect on VZV-specific CD8 T cell response was detected.
Time Frame
At Month 42 after the first vaccination
Secondary Outcome Measure Information:
Title
Frequencies of gE- and VZV-specific CD4/CD8 T Cells With Antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L Secretion/Expression.
Description
The analysis focused on those gE- and VZV-specific CD4 T cells secreting any cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE or VZV was performed, since no long-term vaccine effect on gE- and VZV-specific CD8 T cell response was detected.
Time Frame
At Months 30 and 42 after the first vaccination
Title
Anti-gE Antibody (Ab) Concentrations
Description
As determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and expressed as ELISA units per milliliter (EL.U/mL).
Time Frame
At months 30 and 42 after the first vaccination
Title
Anti-VZV Ab Concentrations
Description
As determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and expressed as ELISA units per milliliter (EL.U/mL).
Time Frame
At months 30 and 42 after the first vaccination
Title
Frequencies of gE-specific Memory B Cells
Description
As determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay.
Time Frame
At months 30 and 42 after the first vaccination
Title
Frequencies of VZV-specific Memory B Cells
Description
As determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay.
Time Frame
At months 30 and 42 after the first vaccination
Title
Number of Subjects With Any Serious Adverse Events (SAEs)
Description
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame
From Month 30 to study end Month 42 after the first vaccination
Title
Number of Subjects With Clinically Diagnosed Herpes Zoster (HZ) Episodes
Description
This assay tabulated the number of subjects with clinically diagnosed HZ episodes, defined as any cutaneous HZ-like rash.
Time Frame
From last primary study visit (Month 12) to study end at Month 42 after the first vaccination.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study; Subjects who successfully completed the primary study and who did not receive Varilrix in the primary study; Written informed consent obtained from the subject; Free of obvious health problems as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) within 1 month preceding the study start, or planned use during the study period; Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first study procedure, including corticosteroids, except inhaled and topical steroids are allowed; Administration or planned administration of a vaccine not foreseen by the study protocol within 2 weeks before the first study procedure, with the exception of the Influenza vaccine, which can be administered 1 week preceding the first study procedure; Previous vaccination against HZ, except the study vaccine administered in the primary study; History of HZ (shingles); Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination; Administration of immunoglobulins and/or any blood products within the 3 months preceding the first study procedure or planned administration during the study period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
30975567
Citation
Keersmaekers N, Ogunjimi B, Van Damme P, Beutels P, Hens N. An ODE-based mixed modelling approach for B- and T-cell dynamics induced by Varicella-Zoster Virus vaccines in adults shows higher T-cell proliferation with Shingrix than with Varilrix. Vaccine. 2019 May 1;37(19):2537-2553. doi: 10.1016/j.vaccine.2019.03.075. Epub 2019 Apr 8.
Results Reference
derived
PubMed Identifier
22872734
Citation
Leroux-Roels I, Leroux-Roels G, Clement F, Vandepapeliere P, Vassilev V, Ledent E, Heineman TC. A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults. J Infect Dis. 2012 Oct;206(8):1280-90. doi: 10.1093/infdis/jis497. Epub 2012 Aug 7.
Results Reference
derived

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Month 30 & 42 Extension Studies of CRD-004 Primary Study

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