Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ/su) Vaccine in Adults With Solid Tumours Receiving Chemotherapy

NCT01798056 | Completed Phase 3 Results

• 2 other identifiers: 1164272012-002966-11
• Study Type: interventional
• Target: 237
• Locations: 6 countries
• Sites: 28

Brief Summary

The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' HZ/su vaccine in adults with solid tumours undergoing chemotherapy.

Conditions

Herpes Zoster; Herpes Zoster Vaccine

Keywords

≥18 years of age; Chemotherapy; Solid tumours; Immunogenicity; Herpes Zoster; Safety; Shingles

Outcome Measures

Primary Outcomes (9)

• Adjusted Geometric Means for Anti-glycoprotein E (gE) Antibodies in PreChemo Groups

  Adjusted geometric means (GMC) of GSK1437173A over placebo for anti-glycoprotein E (gE) antibody enzyme-linked immunosorbent assay (ELISA) concentrations in PreChemo Groups only.

  At Month 2

• Anti-Varicella Zoster Virus (VZV) gE Antibody Concentrations

  Antibody concentrations as determined by ELISA are 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 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 every day activities. 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

• Number of Days With Solicited Local Symptoms

  The number of days with any local symptoms has been assessed during the post-vaccination period.

  During the 7-day (Days 0-6) post-vaccination period following each dose

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, gastrointestinal \[symptoms included nausea, vomiting, diarrhoea and/or abdominal pain\], headache, myalgia, shivering and fever \[defined as oral, axillary or tympanic temperature equal to or above 37.5 degrees Celsius (°C)\]. 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.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Days With Solicited General Symptoms

  The number of days with any general symptoms has been assessed during the post-vaccination period.

  During the 7-day (Days 0-6) post-vaccination period following each dose

• 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

• 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. Related SAE= SAE assessed by the investigator as causally related to the study vaccination.

  From first dose up to 30 days post last vaccination

• 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. Related = pIMDs assessed by the investigator as causally related to the study vaccination.

  From first vaccination up to 30 days post last vaccination

Secondary Outcomes (6)

• Anti-VZV gE Antibody Concentrations

  At Months 0, 1, 6 and 13

• Number of Subjects With Vaccine Responses for Anti-gE Antibody ELISA Concentrations

  At Months 1, 2, 6 and 13

• Descriptive Statistics of the Frequency of gE-specific CD4[2+] T-cells in PreChemo Groups

  At Months 0, 1, 2 and 13

• Number of Subjects With Vaccine Responses for gE-specific CD4[2+] T-cells in PreChemo Groups

  At Months 1, 2 and 13

• Number of Subjects With Serious Adverse Events (SAEs)

  From 30 days post last vaccination up to study end (Month 13)

Study Arms (2)

GSK1437173A Group

EXPERIMENTAL

Subjects received the first dose of GSK 1437173A at least 10 days (up to 1 month) before start of chemotherapy cycle or at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of GSK 1437173A vaccine was administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy. The study products were administered intramuscularly into a deltoid muscle. The choice of and use of chemotherapy, or any other medication related to the patients' current conditions, were based on the local standard of care for the patients.

Biological: GSK 1437173A

Placebo Group

PLACEBO COMPARATOR

Subjects received the first dose of placebo at least 10 days (up to 1 month) before start of chemotherapy cycle or at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of placebo was administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy. The study products were administered intramuscularly into a deltoid muscle. The choice of and use of chemotherapy, or any other medication related to the patients' current conditions, were based on the local standard of care for the patients.

Drug: Placebo

Interventions

GSK 1437173A BIOLOGICAL

2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.

Also known as: HZ/su, GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine

GSK1437173A Group

Placebo DRUG

2 doses administered by IM injection into the deltoid muscle of the non-dominant arm.

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who, in the opinion of the investigator, 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 (and has reached the age of legal consent) at the time of study entry (i.e., when informed consent is signed).
• Subject who has been diagnosed with one or more solid tumours (defined as a solid malignancy, i.e., not a blood element malignancy).
• Subject who is receiving or will receive a cytotoxic or immunosuppressive chemotherapy (such that the study vaccine can be administered at the latest at the start of the second cycle of chemotherapy).
• Life expectancy of greater than one year.
• Female subjects of non-childbearing potential may be enrolled in the study:
• Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause;
• Female subjects of childbearing potential may be enrolled in the study, if the subject:
• has practiced adequate contraception for 30 days prior to vaccination, 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 2 months after completion of the vaccination series.

You may not qualify if:

• Subjects receiving only newer, more targeted therapies if not taken together with a classical chemotherapy.
• Chronic administration and/or planned administration of systemic glucocorticoids within one month prior to the first vaccine dose and up to Visit 3 (Month 2). Inhaled, intra-articularly injected, and topical steroids are allowed.
• Previous vaccination against HZ or varicella within 12 months preceding the first dose of study vaccine/ placebo.
• Planned administration during the study of a HZ vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
• Previous chemotherapy course less than one month before first study vaccination.
• 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.
• Administration or planned administration of a live vaccine in the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine, or, administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.
• HIV infection by clinical history.
• Acute disease and/or fever at the time of vaccination. Acute disease is defined as the presence of a moderate or severe illness with or without fever, but excludes the underlying malignancy, as well as the expected symptoms/signs associated with that disease or its treatment:
• Fever is defined as temperature ≥ 37.5°C /99.5°F on oral, axillary or tympanic setting, or ≥ 38.0°C /100.4°F on rectal setting. The preferred route for recording temperature in this study will be oral.
• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever, may receive the first dose of study vaccine/ placebo at the discretion of the investigator.
• Any condition which, in the judgment of the investigator would make intramuscular injection unsafe.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 3 (i.e., 2 months after the last dose of study vaccine/ placebo).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (28)

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4C 3E7, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4J 1C5, Canada

Location

GSK Investigational Site

Prague, 180 00, Czechia

Location

GSK Investigational Site

Besançon, 25030, France

Location

GSK Investigational Site

Férolles-Attilly, 77150, France

Location

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Nîmes, 30029, France

Location

GSK Investigational Site

Seoul, 02841, South Korea

Location

GSK Investigational Site

Seoul, 03080, South Korea

Location

GSK Investigational Site

Seoul, 05505, South Korea

Location

GSK Investigational Site

Badajoz, 6080, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

Location

GSK Investigational Site

Móstoles, 28935, Spain

Location

GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

Location

GSK Investigational Site

San Sebastián de los Reyes, 28702, Spain

Location

GSK Investigational Site

Cheltenham, Gloucestershire, GL53 7AN, United Kingdom

Location

GSK Investigational Site

Woolwich, London, SE18 4QH, United Kingdom

Location

GSK Investigational Site

Swindon, Wiltshire, SN3 6BB, United Kingdom

Location

GSK Investigational Site

Exeter, EX2 5DW, United Kingdom

Location

GSK Investigational Site

Sheffield, S10 2SJ, United Kingdom

Location

GSK Investigational Site

York, YO31 8HE, United Kingdom

Location

Related Publications (2)

• Vink P, Delgado Mingorance I, Maximiano Alonso C, Rubio-Viqueira B, Jung KH, Rodriguez Moreno JF, Grande E, Marrupe Gonzalez D, Lowndes S, Puente J, Kristeleit H, Farrugia D, McNeil SA, Campora L, Di Paolo E, El Idrissi M, Godeaux O, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L; Zoster-028 Study Group. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial. Cancer. 2019 Apr 15;125(8):1301-1312. doi: 10.1002/cncr.31909. Epub 2019 Feb 1.

  PMID: 30707761 BACKGROUND

• Hirsch C, Zorger AM, Baumann M, Park YS, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with solid tumours. Cochrane Database Syst Rev. 2025 Apr 16;4(4):CD015551. doi: 10.1002/14651858.CD015551.pub2.

  PMID: 40237463 DERIVED

Related Links

• Full CSR posting on gsk.

MeSH Terms

Conditions

Herpes Zoster

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: February 25, 2013
• Study Start: March 6, 2013
• Primary Completion: June 18, 2015
• Study Completion: May 20, 2016
• Last Updated: May 13, 2021
• Results First Posted: August 17, 2018

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CA (3); FR (4); KR (3); CZ (1); ES (11); GB (6)