Clinical trial NCT00434577: Safety and Immunogenicity of the Zoster Vaccine GSK1437173A in Elderly Subjects
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Herpes Zoster
Keywords: GSK Biologicals
Herpes Zoster (HZ)
Vaccine
Varicella Zoster Virus (VZV)
Shingles
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-02-13
Enrollment: 715
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).
* 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.

Primary outcomes:
measure: Frequency of Glycoprotein E (gE)-Specific Cluster of Differentiation (CD4) T-cells Expressing at Least Two Different Activation Markers
timeFrame: One month after the second vaccination (Month 3)
measure: Frequency Odds Ratio of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
timeFrame: One month after the second vaccination (Month 3)
measure: Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
timeFrame: One month after the second vaccination (Month 3)
Secondary outcomes:
measure: Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD4 T-cells Expressing IFN-γ and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD4 T-cells Expressing IL-2 and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD4 T-cells Expressing TNF-α and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD4 T-cells Expressing CD40L and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD8 T-cells Expressing at Least Two Different Activation Markers
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD8 T-cells Expressing TNF-α and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD8 T-cells Expressing CD40L and at Least Another Activation Marker
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Anti-gE Specific Antibody Concentrations
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
timeFrame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
measure: Frequency of gE-specific CD4/CD8 T-cells Expressing at Least Two Different Activation Markers
timeFrame: At Months 12, 24 and 36
measure: Frequency of gE-specific CD4/CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
timeFrame: At Months 12, 24 and 36
measure: Frequency of gE-specific CD4/CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
timeFrame: At Months 12, 24 and 36
measure: Frequency of gE-specific CD4/CD8 T-cells Expressing TNFα and at Least Another Activation Marker
timeFrame: At Month 12, 24 and 36
measure: Frequency of gE-specific CD4/CD8 T-cells Expressing CD40L and at Least Another Activation Marker
timeFrame: At Month 12, 24 and 36
measure: Anti-gE Specific Antibody Concentrations
timeFrame: At Months 12, 24 and 36
measure: Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
timeFrame: At Months 12, 24 and 36
measure: Frequency of VZV-specific Memory B-cells in a Subset of Subjects
timeFrame: At pre-vaccination (Day 0) and at Month 3
measure: Number of Subjects With Different Biochemical and Haematological Levels
timeFrame: At Day 0, Month 2 and Month 3
measure: Number of German Subjects With Different Biochemical and Haematological Levels
timeFrame: At one week post-vaccination 1 (Month 0)
measure: Number of German Subjects With Different Biochemical and Haematological Levels
timeFrame: At one week post-vaccination 2 (Month 2)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Occurrence of Clinically Diagnosed Herpes Zoster (HZ) Episodes
timeFrame: From Month 0 to Month 3
measure: Number of Subjects With Occurrence of Clinically Diagnosed HZ Episodes
timeFrame: From Month 3 up to Month 36
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Month 0 to Month 3
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Month 3 to Month 12
Other outcomes:
Locations:
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Eskilstuna
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Schwarz 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.