Herpes ZosterPhase 2NCT00434577
Safety and Immunogenicity of the Zoster Vaccine GSK1437173A in Elderly Subjects
A Phase 2 study testing Herpes Zoster vaccine GSK1437173A Low Dose, Herpes Zoster vaccine GSK1437173A Medium Dose and Herpes Zoster vaccine GSK1437173A High Dose in people with Herpes Zoster, run by GlaxoSmithKline at 11 sites in 4 countries.
Trial summary
Based on the results of a previous clinical PhaseI/II study, GSK1437173A is the lead GSK candidate Herpes Zoster (HZ) vaccine to prevent episodes of HZ (shingles). This phase II study will be subdivided into a primary study (108494) and three extension studies (108516, 108518 \& 108520), consisting of one additional… Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Herpes Zoster
- What is being tested?
- Herpes Zoster vaccine GSK1437173A Low Dose, Herpes Zoster vaccine GSK1437173A Medium Dose and Herpes Zoster vaccine GSK1437173A High Dose
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 715 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 14 Feb 2007to 14 Jul 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
- A male or female aged 60 years or older at the time of the first vaccination.
- Written informed consent obtained from the subject
Who cannot join
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first injection with study vaccine, or planned use during the study period.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the study period, except inhaled and topical steroids are allowed.
- Administration or planned administration of a vaccine not foreseen by the study protocol within 2 weeks of the first study vaccine injection, with the exception of the influenza vaccine, which can be administered 1 week preceding or 1 month after the first study vaccine injection.
- Previous vaccination against HZ.
- History of herpes zoster (Shingles).
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
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- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- Acute disease at the time of enrolment.
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by subject's medical history or physical examination as assessed by the investigator.
- Administration of immunoglobulins and/or any blood products within the 3 months preceding the first injection of study vaccine or planned administration during the study period.
- History of or current drug and/or alcohol abuse.
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
Germany6 sites
GSK Investigational Site
Berlin, 13347
GSK Investigational Site
Cologne, North Rhine-Westphalia, 51069
GSK Investigational Site
Essen, North Rhine-Westphalia, 45359
GSK Investigational Site
Hanover, Lower Saxony, 30625
GSK Investigational Site
Mannheim, Baden-Wurttemberg, 68161
GSK Investigational Site
Würzburg, Bavaria, 97070
Netherlands2 sites
GSK Investigational Site
Amsterdam, 1018 WT
GSK Investigational Site
Rotterdam, 3011 EN
Sweden2 sites
GSK Investigational Site
Eskilstuna, SE-631 88
GSK Investigational Site
Uppsala, SE-751 85
About this study
Official title: A Phase II, Single-blind, Randomized, Controlled, Multicentre Vaccination Study to Evaluate the Safety and Immune Response of the GSK Biologicals Zoster Vaccine, gE/AS01B, and to Compare 3 Doses of gE With AS01B Adjuvant in Healthy Elderly Subjects, Aged 60 to 69 Years and 70 Years and Above.
Based on the results of a previous clinical PhaseI/II study, GSK1437173A is the lead GSK candidate Herpes Zoster (HZ) vaccine to prevent episodes of HZ (shingles). This phase II study will be subdivided into a primary study (108494) and three extension studies (108516, 108518 \& 108520), consisting of one additional visit each at months 12, 24 and 36, respectively, from the first visit of the Zoster-003 primary study onwards. The aim of the primary 108494 study is to evaluate the immunogenicity \& safety of different dosages of the GSK1437173A vaccine in healthy elderly population. The study population will be stratified by age. The primary objective of this trial is to select the best dosage of GSK1437173A. The aim of the extension studies is to evaluate the persistence of the immune response induced by the candidate HZ vaccine during a long term period.
No new subjects will be enrolled during the extension phases of the study.
Read the detailed description
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
- Conditions
- Herpes Zoster
- Being tested
- Herpes Zoster vaccine GSK1437173A Low Dose, Herpes Zoster vaccine GSK1437173A Medium Dose, Herpes Zoster vaccine GSK1437173A High Dose, Herpes Zoster vaccine GSK1437173A Modified, Placebo
- Keywords
- GSK Biologicals, Herpes Zoster (HZ), Vaccine, Varicella Zoster Virus (VZV), Shingles
- Medical subject headings
- Herpes Zoster, Chickenpox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Herpes Zoster vaccine GSK1437173A Low DoseBiological
Single or two-dose intramuscular injection.
Herpes Zoster vaccine GSK1437173A Medium DoseBiological
Single or two-dose intramuscular injection.
Herpes Zoster vaccine GSK1437173A High DoseBiological
Single or two-dose intramuscular injection.
Herpes Zoster vaccine GSK1437173A ModifiedBiological
Single or two-dose intramuscular injection.
PlaceboBiological
Single intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| GSK1437173A _LD Group | Experimental | Healthy male or female subjects aged 60 years or older, who received 2 doses of herpes zoster subunit vaccine (GSK1437173A) low dose (LD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by intramuscular injection (IM) in the upper deltoid site of the left arm. Receives: Biological: Herpes Zoster vaccine GSK1437173A Low Dose |
| GSK1437173A _MD Group | Experimental | Healthy male or female subjects aged 60 years or older, who received 2 doses of herpes zoster subunit vaccine (GSK1437173A) medium dose (MD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. Receives: Biological: Herpes Zoster vaccine GSK1437173A Medium Dose |
| GSK1437173A _HD Group | Experimental | Healthy male or female subjects aged 60 years or older, who received 2 doses of herpes zoster subunit vaccine (GSK1437173A) high dose (HD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. Receives: Biological: Herpes Zoster vaccine GSK1437173A High Dose |
| Placebo + GSK1437173A _HD Group | Placebo comparator | Healthy male or female subjects aged 60 years or older, who received a 1st dose of saline solution and a 2nd dose of GSK1437173A high dose (HD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. Receives: Biological: Herpes Zoster vaccine GSK1437173A High Dose; Biological: Placebo |
| GSK1437173A_MODIFIED GROUP | Active comparator | Healthy male or female subjects aged 60 years or older, who received 2 doses of GSK1437173A modified formulation vaccine reconstituted with saline solution, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. Receives: Biological: Herpes Zoster vaccine GSK1437173A Modified |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Glycoprotein E (gE)-Specific Cluster of Differentiation (CD4) T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects aged 70 or higher (≥).
Measured: One month after the second vaccination (Month 3)
Frequency Odds Ratio of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects ≥ 70 years old. The odds-ratios are calculated using the the frequency of CD4 secreting cytokines, upon in vitro stimulation with the specific antigen, at the numerator and the frequency of the CD4 secreting cytokines with the medium only (background level) at the denominator. The odds-ratios represent the fold-change in the specific response compared to the background level.
Measured: One month after the second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects ≥ 70 years old.
Measured: One month after the second vaccination (Month 3)
Secondary outcomes (30)
Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects 60 to 69 years (60-69y) and ≥ 70 years (+70y) old.
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing IFN-γ and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or tumour necrosis factor-alpha [TNF-α] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing IL-2 and at Least Another Activation Marker
Among other activation markers expressed were interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing TNF-α and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing CD40L and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α] . Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or tumour necrosis factor-alpha [TNF-α] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
Among other activation markers expressed were interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing TNF-α and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing CD40L and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Anti-gE Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL), as assessed by ELISA.
Measured: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4/CD8 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Measured: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or tumour necrosis factor-alpha [TNF-α] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Measured: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
Among other activation markers expressed were interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Measured: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing TNFα and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Measured: At Month 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing CD40L and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α] . Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Measured: At Month 12, 24 and 36
Anti-gE Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Measured: At Months 12, 24 and 36
Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).
Measured: At Months 12, 24 and 36
Frequency of VZV-specific Memory B-cells in a Subset of Subjects
Memory B cells specific to the gE antigen, as assessed by the enzyme-linked immunosorbent spot (ELISPOT) method, were expressed as a frequency of the specific memory B-cells per million memory B-cells. Results were tabulated for subjects aged 70 years and older.
Measured: At pre-vaccination (Day 0) and at Month 3
Number of Subjects With Different Biochemical and Haematological Levels
Among biochemical and haematological parameters assessed were albumin [ALB], alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], calcium [CAL], eosinophils [EOS], fibrinogen [FIB], haematocrit [HEM], hemoglobin [Hgb], leucocytes [LEU], lymphocytes [LYM], lactate dehydrogenate [LDH], monocytes [MON], neutrophils [NEU], partial thromboplastin time [PTPT], platelets [PLA], pro thrombin time [PTT], red blood cells [RBC], serum creatinine [SCREA], total protein [TP]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - unknown, below, within and above.
Measured: At Day 0, Month 2 and Month 3
Number of German Subjects With Different Biochemical and Haematological Levels
Among biochemical and haematological parameters assessed were albumin [ALB], calcium [CAL], fibrinogen [FIB], lactate dehydrogenase [LDH], partial thrombo-plastin time [PTPT], pro thrombin time [PTT], total protein [TP]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - below, within, above and missing, as compared to the pre-vaccination status (below, within, above or missing). Values for electrophoresis (globulins and albumin/globulin ratio) were not displayed.
Measured: At one week post-vaccination 1 (Month 0)
Number of German Subjects With Different Biochemical and Haematological Levels
Among biochemical and haematological parameters assessed were albumin [ALB], calcium [CAL], fibrinogen [FIB], lactate dehydrogenase [LDH], partial thrombo-plastin time [PTPT], pro thrombin time [PTT], total protein [TP]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - below, within, above and missing, as compared to the pre-vaccination status (below, within, above or missing). Values for electrophoresis (globulins and albumin/globulin ratio) were not displayed.
Measured: At one week post-vaccination 2 (Month 2)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Measured: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache and myalgia. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Measured: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Occurrence of Clinically Diagnosed Herpes Zoster (HZ) Episodes
Clinically diagnosed episodes included rash that was assessed by hives, idiopathic thrombocytopenic purpura, petechiae.
Measured: From Month 0 to Month 3
Number of Subjects With Occurrence of Clinically Diagnosed HZ Episodes
Clinically diagnosed episodes included rash that was assessed by hives, idiopathic thrombocytopenic purpura, petechiae.
Measured: From Month 3 up to Month 36
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Measured: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: From Month 0 to Month 3
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: From Month 3 to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2007 (estimated)
- Study start14 Feb 2007
- Primary completion4 Oct 2007
- Study completion14 Jul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Herpes ZosterStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 715 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00434577
- Sponsor's protocol ID
- 108494
- Other IDs
- 108516, 108518, 108520, 2006-004863-69
- Status last verified
- Feb 2019
- First submitted
- 12 Feb 2007
- Last updated
- 15 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Chlibek R, Smetana J, Pauksens K, Rombo L, Van den Hoek JA, Richardus JH, Plassmann G, Schwarz TF, Ledent E, Heineman TC. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine. 2014 Mar 26;32(15):1745-53. doi: 10.1016/j.vaccine.2014.01.019. Epub 2014 Feb 6.
PubMed 24508036Schwarz TF, Volpe S, Catteau G, Chlibek R, David MP, Richardus JH, Lal H, Oostvogels L, Pauksens K, Ravault S, Rombo L, Sonder G, Smetana J, Heineman T, Bastidas A. Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults. Hum Vaccin Immunother. 2018 Jun 3;14(6):1370-1377. doi: 10.1080/21645515.2018.1442162. Epub 2018 Mar 21.
PubMed 29461919
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-blind, Randomized, Controlled, Multicentre Vaccination Study to Evaluate the Safety and Immune Response of the GSK Biologicals Zoster Vaccine, gE/AS01B, and to Compare 3 Doses of gE With AS01B Adjuvant in Healthy Elderly Subjects, Aged 60 to 69 Years and 70 Years and Above.
- ClinicalTrials.gov ID
- NCT00434577
- Acronym / sponsor ID
- 108494
- Conditions
- Herpes Zoster
- Keywords
- GSK Biologicals, Herpes Zoster (HZ), Vaccine, Varicella Zoster Virus (VZV), Shingles
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 715 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2007 (actual)
- Primary completion
- 4 Oct 2007 (actual)
- Study completion
- 14 Jul 2010 (actual)
- First posted
- 13 Feb 2007 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Based on the results of a previous clinical PhaseI/II study, GSK1437173A is the lead GSK candidate Herpes Zoster (HZ) vaccine to prevent episodes of HZ (shingles). This phase II study will be subdivided into a primary study (108494) and three extension studies (108516, 108518 \& 108520), consisting of one additional visit each at months 12, 24 and 36, respectively, from the first visit of the Zoster-003 primary study onwards. The aim of the primary 108494 study is to evaluate the immunogenicity \& safety of different dosages of the GSK1437173A vaccine in healthy elderly population. The study population will be stratified by age. The primary objective of this trial is to select the best dosage of GSK1437173A. The aim of the extension studies is to evaluate the persistence of the immune response induced by the candidate HZ vaccine during a long term period.
No new subjects will be enrolled during the extension phases of the study.
Detailed description
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| GSK1437173A _LD Group | Experimental | Biological: Herpes Zoster vaccine GSK1437173A Low DoseHealthy male or female subjects aged 60 years or older, who received 2 doses of herpes zoster subunit vaccine (GSK1437173A) low dose (LD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by intramuscular injection (IM) in the upper deltoid site of the left arm. |
| GSK1437173A _MD Group | Experimental | Biological: Herpes Zoster vaccine GSK1437173A Medium DoseHealthy male or female subjects aged 60 years or older, who received 2 doses of herpes zoster subunit vaccine (GSK1437173A) medium dose (MD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. |
| GSK1437173A _HD Group | Experimental | Biological: Herpes Zoster vaccine GSK1437173A High DoseHealthy male or female subjects aged 60 years or older, who received 2 doses of herpes zoster subunit vaccine (GSK1437173A) high dose (HD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. |
| Placebo + GSK1437173A _HD Group | Placebo comparator | Biological: Herpes Zoster vaccine GSK1437173A High Dose, Biological: PlaceboHealthy male or female subjects aged 60 years or older, who received a 1st dose of saline solution and a 2nd dose of GSK1437173A high dose (HD) formulation, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. |
| GSK1437173A_MODIFIED GROUP | Active comparator | Biological: Herpes Zoster vaccine GSK1437173A ModifiedHealthy male or female subjects aged 60 years or older, who received 2 doses of GSK1437173A modified formulation vaccine reconstituted with saline solution, according to a 0, 2-month schedule. The vaccine was administrated by (IM) in the upper deltoid site of the left arm. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
- A male or female aged 60 years or older at the time of the first vaccination.
- Written informed consent obtained from the subject
Key exclusion criteria (11 listed)
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first injection with study vaccine, or planned use during the study period.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the study period, except inhaled and topical steroids are allowed.
- Administration or planned administration of a vaccine not foreseen by the study protocol within 2 weeks of the first study vaccine injection, with the exception of the influenza vaccine, which can be administered 1 week preceding or 1 month after the first study vaccine injection.
- Previous vaccination against HZ.
- History of herpes zoster (Shingles).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Herpes Zoster vaccine GSK1437173A Low DoseSingle or two-dose intramuscular injection. | Biological | GSK1437173A _LD Group |
| Herpes Zoster vaccine GSK1437173A Medium DoseSingle or two-dose intramuscular injection. | Biological | GSK1437173A _MD Group |
| Herpes Zoster vaccine GSK1437173A High DoseSingle or two-dose intramuscular injection. | Biological | GSK1437173A _HD Group, Placebo + GSK1437173A _HD Group |
| Herpes Zoster vaccine GSK1437173A ModifiedSingle or two-dose intramuscular injection. | Biological | GSK1437173A_MODIFIED GROUP |
| PlaceboSingle intramuscular injection | Biological | Placebo + GSK1437173A _HD Group |
Primary outcome
Frequency of Glycoprotein E (gE)-Specific Cluster of Differentiation (CD4) T-cells Expressing at Least Two Different Activation Markers
Time frame: One month after the second vaccination (Month 3)
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects aged 70 or higher (≥).
Frequency Odds Ratio of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Time frame: One month after the second vaccination (Month 3)
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects ≥ 70 years old. The odds-ratios are calculated using the the frequency of CD4 secreting cytokines, upon in vitro stimulation with the specific antigen, at the numerator and the frequency of the CD4 secreting cytokines with the medium only (background level) at the denominator. The odds-ratios represent the fold-change in the specific response compared to the background level.
Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Time frame: One month after the second vaccination (Month 3)
Among the activation markers expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects ≥ 70 years old.
30 secondary outcomes
Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing IFN-γ and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing IL-2 and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing TNF-α and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing CD40L and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing at Least Two Different Activation Markers
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing TNF-α and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing CD40L and at Least Another Activation Marker
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Anti-gE Specific Antibody Concentrations
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4/CD8 T-cells Expressing at Least Two Different Activation Markers
Time frame: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
Time frame: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
Time frame: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing TNFα and at Least Another Activation Marker
Time frame: At Month 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing CD40L and at Least Another Activation Marker
Time frame: At Month 12, 24 and 36
Anti-gE Specific Antibody Concentrations
Time frame: At Months 12, 24 and 36
Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
Time frame: At Months 12, 24 and 36
Frequency of VZV-specific Memory B-cells in a Subset of Subjects
Time frame: At pre-vaccination (Day 0) and at Month 3
Number of Subjects With Different Biochemical and Haematological Levels
Time frame: At Day 0, Month 2 and Month 3
Number of German Subjects With Different Biochemical and Haematological Levels
Time frame: At one week post-vaccination 1 (Month 0)
Number of German Subjects With Different Biochemical and Haematological Levels
Time frame: At one week post-vaccination 2 (Month 2)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Occurrence of Clinically Diagnosed Herpes Zoster (HZ) Episodes
Time frame: From Month 0 to Month 3
Number of Subjects With Occurrence of Clinically Diagnosed HZ Episodes
Time frame: From Month 3 up to Month 36
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Time frame: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: From Month 0 to Month 3
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: From Month 3 to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24508036Chlibek R, Smetana J, Pauksens K, Rombo L, Van den Hoek JA, Richardus JH, Plassmann G, Schwarz TF, Ledent E, Heineman TC. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine. 2014 Mar 26;32(15):1745-53. doi: 10.1016/j.vaccine.2014.01.019. Epub 2014 Feb 6.
- Derived from this study: PubMed 29461919Schwarz TF, Volpe S, Catteau G, Chlibek R, David MP, Richardus JH, Lal H, Oostvogels L, Pauksens K, Ravault S, Rombo L, Sonder G, Smetana J, Heineman T, Bastidas A. Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults. Hum Vaccin Immunother. 2018 Jun 3;14(6):1370-1377. doi: 10.1080/21645515.2018.1442162. Epub 2018 Mar 21.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Herpes Zoster vaccine GSK1437173A Low Dose, Herpes Zoster vaccine GSK1437173A Medium Dose and Herpes Zoster vaccine GSK1437173A High Dose in people with Herpes Zoster, run by GlaxoSmithKline at 11 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Germany, Netherlands, Sweden, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Glycoprotein E (gE)-Specific Cluster of Differentiation (CD4) T-cells Expressing at Least Two Different Activation Markers (time frame: One month after the second vaccination (Month 3)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00434577, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2019.