Study to Evaluate Efficacy, Safety, and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Vaccine GSK1437173A

Herpes Zoster Clinical Trial

Official title:

Observer-blind Study to Evaluate Efficacy, Safety, and Immunogenicity of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01610414
• Other study ID #: 115523
• Secondary ID: 2012-000138-20
• Status: Completed
• Phase: Phase 3
• First received: May 31, 2012
• Last updated: December 20, 2017
• Start date: July 13, 2012
• Est. completion date: February 1, 2017

Study information

• Verified date: December 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of GSK Biologicals' vaccine GSK1437173A in the prevention of Herpes zoster (HZ) in autologous haematopoietic cell transplant recipients 18 years of age and older. To this end, the study will evaluate vaccine efficacy (VE) of the GSK1437173A vaccine, administered on a 2-dose schedule, compared to placebo in reducing the risk of developing HZ in this population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1877
• Est. completion date: February 1, 2017
• Est. primary completion date: November 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Study entry (enrollment) occurs at the Pre-vaccination visit.

• Subjects who the investigator believes can and will comply with the requirements of the protocol.

• Written informed consent obtained from the subject.

• A male or female aged 18 years or older at the time of study entry.

• Has undergone or will undergo autologous HCT within 50-70 days prior to the first vaccination with the study vaccine/placebo, and there are no plans for additional HCTs.

• Female subjects of non-childbearing potential may be enrolled in the study. For this study population, non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause.

OR Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for 30 days prior to vaccination with the study vaccine/placebo, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 12 months after completion of the vaccination series (i.e., until Month 13).

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/placebo, or planned use during the study period. However, the investigational use of a registered or non-registered product to treat the subject's underlying disease for which the HCT was undertaken, or a complication of the underlying disease, is allowed.

• Previous vaccination against HZ or varicella within the 12 months preceding the first dose of study vaccine/placebo.

• Planned administration during the study of a HZ vaccine other than the study vaccine.

• Occurrence of a varicella or HZ episode by clinical history within the 12 months preceding the first dose of study vaccine/placebo.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or study material and equipment.

• Prophylactic antiviral therapy with activity against Varicella Zoster Virus (VZV) expected to last more than 6 months after transplantation.

• Administration and/or planned administration of a vaccine not foreseen by the study protocol between HCT and 30 days after the last dose of study vaccine/placebo. However, licensed non-replicating vaccines may be administered up to 8 days prior to dose 1and/or 2, and/or at least 14 days after any dose of study vaccine/placebo.

• HIV infection by clinical history.

• Pregnant or lactating female.

• Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 13 (i.e., one year after the last dose of study vaccine/placebo).

Related Conditions & MeSH terms

• Herpes Zoster

Intervention

Biological:
• Herpes Zoster vaccine GSK1437173A
2 doses administered intramuscularly (IM) in deltoid region of non-dominant arm
• Placebo
2 doses administered IM in deltoid region of non-dominant arm

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Box Hill	Victoria
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	East Melbourne	Victoria
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Hobart	Tasmania
Australia	GSK Investigational Site	Parkville	Victoria
Australia	GSK Investigational Site	Waratah	New South Wales
Australia	GSK Investigational Site	Westmead	New South Wales
Australia	GSK Investigational Site	Woodville	South Australia
Belgium	GSK Investigational Site	Antwerpen
Belgium	GSK Investigational Site	Brugge
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Hasselt
Belgium	GSK Investigational Site	Jette
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liege
Bulgaria	GSK Investigational Site	Sofia
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Saint John	New Brunswick
Canada	GSK Investigational Site	Saskatoon	Saskatchewan
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Czechia	GSK Investigational Site	Hradec Kralove
Czechia	GSK Investigational Site	Olomouc
Czechia	GSK Investigational Site	Praha 10
Czechia	GSK Investigational Site	Praha 2
Estonia	GSK Investigational Site	Tallinn
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
France	GSK Investigational Site	Clermont-Ferrand Cedex 1
France	GSK Investigational Site	Créteil cedex
France	GSK Investigational Site	Grenoble cedex 9
France	GSK Investigational Site	Marseille cedex 9
France	GSK Investigational Site	Montpellier cedex 5
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Rouen cedex 1
Germany	GSK Investigational Site	Bayreuth	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Eschweiler	Nordrhein-Westfalen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Velbert	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wuerzburg	Bayern
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Thessaloniki
Hong Kong	GSK Investigational Site	Hong Kong
Hong Kong	GSK Investigational Site	Tuen Mun
Israel	GSK Investigational Site	Hafia
Israel	GSK Investigational Site	Jerusalem
Italy	GSK Investigational Site	Aviano (PN)	Friuli-Venezia-Giulia
Italy	GSK Investigational Site	Cona (FE)	Emilia-Romagna
Italy	GSK Investigational Site	Meldola (FC)	Emilia-Romagna
Italy	GSK Investigational Site	Novara	Piemonte
Italy	GSK Investigational Site	Ravenna	Emilia-Romagna
Italy	GSK Investigational Site	Rimini	Emilia-Romagna
Italy	GSK Investigational Site	Rozzano (MI)	Lombardia
Italy	GSK Investigational Site	Udine	Friuli-Venezia-Giulia
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Niigata
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Jellanamdo
Korea, Republic of	GSK Investigational Site	Jeonju
Korea, Republic of	GSK Investigational Site	Kyunggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Malaysia	GSK Investigational Site	Kuala Lumpur
Malaysia	GSK Investigational Site	Selangor
Netherlands	GSK Investigational Site	Leiden
New Zealand	GSK Investigational Site	Christchurch
New Zealand	GSK Investigational Site	Grafton
New Zealand	GSK Investigational Site	Wellington
Panama	GSK Investigational Site	Panama
Poland	GSK Investigational Site	Gliwice
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Warszawa
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Tirgu Mures
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Petrozavodsk
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St.-Petersburg
Russian Federation	GSK Investigational Site	St.Petersburg
South Africa	GSK Investigational Site	Groenkloof
South Africa	GSK Investigational Site	Moreleta Park, Pretoria
South Africa	GSK Investigational Site	Parktown	Gauteng
South Africa	GSK Investigational Site	Plumstead	Western Province
Spain	GSK Investigational Site	Badalona/Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	La Coruña
Spain	GSK Investigational Site	León
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda (Madrid)
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Murcia (El Palmar)
Spain	GSK Investigational Site	Oviedo
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	San Sebastián
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taoyuan Hsien
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Izmir
United Kingdom	GSK Investigational Site	Airdrie	Lanarkshire
United Kingdom	GSK Investigational Site	Bournemouth
United Kingdom	GSK Investigational Site	Cottingham
United Kingdom	GSK Investigational Site	Headington, Oxford
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Swindon	Wiltshire
United States	GSK Investigational Site	Aurora	Colorado
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Duarte	California
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Hackensack	New Jersey
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Marshfield	Wisconsin
United States	GSK Investigational Site	Minnesota	Minnesota
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  New Zealand,  Panama,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Confirmed Herpes Zoster (HZ) Episode	A suspected case of HZ was defined as (1) a new rash characteristic of HZ (e.g., unilateral, dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or other sensations), or a vesicular rash suggestive of VZV infection regardless of the distribution, and no alternative diagnosis; or (2) a clinical presentation (symptoms and/or signs) and specific laboratory findings* suggestive of VZV infection in the absence of characteristic HZ or VZV rash.; A suspected case of HZ was confirmed either: by Polymerase Chain Reaction (PCR) or by the HZ Ascertainment Committee (HZAC), consisting of physicians with HZ expertise.	From Month 0 until the cut-off date for final analysis (median follow-up was of 21 months)
Secondary	Duration of 'Worst' HZ-associated Pain	Duration of HZ-associated pain rated as 3 or greater on the 'worst pain' Zoster Brief Pain Inventory (ZBPI) question, following the onset of a confirmed HZ rash over the entire pain reporting period in subjects with confirmed HZ; presented as T (day) [=the sum of follow-up period (for subjects without severe worst pain T is 1, for subjects with severe worst pain T is the duration of severe worst pain) expressed in days].	From Month 0 until study end (4 years approximately), from the onset of a confirmed HZ rash over the entire pain reporting period
Secondary	Number of Subjects With Confirmed HZ-associated Complications	This analysis excluded complications that were linked to a confirmed HZ case that occurred after the start of the relapse treatment.	From Month 0 until the cut-off date for final analysis (median follow-up was of 21 months)
Secondary	Number of Subjects With Postherpetic Neuralgia (PHN)	This analysis excluded PHN episodes that were linked to a confirmed HZ case that occurred after the start of the relapse treatment.	From Month 0 until study end (21 months median follow-up)
Secondary	Antigen-glycoprotein E (gE) Antibody Concentrations in a Sub-cohort of Subjects	Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (=) 97 mIU/mL.	At Months 0, 1, 2, 13 and 25
Secondary	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.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever [defined as axillary/tympanic temperature equal to or above 37.5 degrees Celsius (°C) or rectal temperature equal to or above 38.0 °C]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Secondary	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.	During the 30-day (Days 0-29) post-vaccination period
Secondary	Number of Subjects With Any and Related Potential Immune Mediated Diseases (pIMDs)	Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.	From Month 0 up to 365 days post last vaccination
Secondary	Number of Subjects With Any Relapse	Relapse was defined as the occurrence of the underlying malignancy or disease for which the HCT was undertaken.	From Month 0 until study end (approximate median of 29 months follow-up - minimum 1 year and maximum 4 years)
Secondary	Number of Subjects With Any Serious Adverse Events (SAEs) and Related SAEs to GSK Study Vaccine/Placebo	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. This enpoint also presents SAES related to the GSK study vaccine/placebo.	From Month 0 until 365 days post last vaccination (approximate median of 29 months follow-up - minimum 1 year and maximum 4 years)
Secondary	Number of Subjects With Fatal SAEs and SAEs Related to Study Participation or to a GSK Concomitant Medication or Vaccination	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. This endpoint presents fatal SAEs and SAEs related to study participation or to a concurrent GSK medication/vaccine.	From the Pre-vaccination visit (Up to 110 days prior Month 0) until study end (approximate median of 29 months follow-up minimum 1 year and maximum 4 years)