A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline's Herpes Zoster Subunit Vaccine (HZ/su) When Given on a Two-dose Schedule to Adults at Least 50 Years of Age (YOA) Who Had Prior Episode of Shingles

• ClinicalTrials.gov Identifier: NCT04091451
• Recruitment Status: Active, not recruiting
• First Posted: September 16, 2019
• Last Update Posted: May 9, 2022
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study is to assess the safety and immunogenicity of GSK Biologicals' HZ/su vaccine when given on a two-dose schedule to adults aged 50 years and above who have had a previous episode of shingles.

Condition or disease	Intervention/treatment	Phase
Herpes Zoster	Biological: Herpes Zoster subunit (HZ/su) vaccine (GSK1437173A); Drug: Placebo	Phase 3

Detailed Description:

The study will be conducted in 2 epochs: Epoch 001- starting from visit day 1, followed by visit month 2 and then Visit 3 at one month post last vaccination (Month 3). Epoch 002- Starting with monthly contact after Visit 3 (Month 3) and ending at 26 months from the enrolment date.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1426 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit Vaccine (HZ/su) GSK1437173A on a Two-dose Schedule in Adults ≥ 50 Years of Age With a Prior Episode of Herpes Zoster
• Actual Study Start Date: September 17, 2019
• Estimated Primary Completion Date: January 22, 2024
• Estimated Study Completion Date: January 22, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: HZ/su Group; Subjects randomized to the HZ/su group will receive 2 doses of HZ/su vaccine at visit day 1 and visit month 2 and will be followed up until the study end.	Biological: Herpes Zoster subunit (HZ/su) vaccine (GSK1437173A); 2 doses of the HZ/su vaccine in a 0,2 Months schedule, administered intramuscularly
Placebo Comparator: Placebo Group; Subjects randomized to Placebo group will receive placebo at visit day 1 and visit month 2 and will be followed up until the study end.	Drug: Placebo; 2 doses of the placebo in a 0,2 Months schedule, administered intramuscularly

Outcome Measures

Primary Outcome Measures :

1. Number of confirmed Herpes Zoster (HZ) cases [ Time Frame: From one-month post-dose 2 (i.e. Month 3) to study end (i.e. Month 26) ]
   A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A suspected case of HZ is confirmed by 2 ways: - By PCR (Polymerase Chain Reaction). - By the HZ Ascertainment Committee (HZAC). The incidence of HZ recurrence in the HZ/su group versus placebo group is compared by performing a non-inferiority analysis.

Secondary Outcome Measures :

1. Number of confirmed HZ cases [ Time Frame: From Visit Day 1 till study end (Month 26) ]
   A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A suspected case of HZ is confirmed by 2 ways: - By PCR (Polymerase Chain Reaction). - By the HZ Ascertainment Committee (HZAC).
2. Number of subjects with any solicited local adverse events (AEs) [ Time Frame: Within 7 days after each vaccination (Vaccines administered on Day 1 and Month 2) ]
   An AE is 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. Assessed solicited local AEs are pain, redness swelling and itching at the injection site. Any = occurrence of the AE regardless of intensity grade.
3. Number of subjects with any solicited general adverse events (AEs) [ Time Frame: Within 7 days after each vaccination (Vaccines administered on Day 1 and Month 2) ]
   An AE is 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. Assessed solicited general AEs are fatigue, fever (defined as axillary temperature ≥ 38.0°C / 100.4°F), gastrointestinal symptoms, headache, myalgia, shivering and malaise. Any = occurrence of the AE regardless of intensity grade.
4. Number of subjects with any unsolicited AEs [ Time Frame: Within 30 days after each vaccination (Vaccines administered on Day 1 and Month 2) ]
   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. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
5. Number of subjects with any serious adverse events (SAEs) [ Time Frame: From Visit Day 1 up to 30 days post last vaccination (i.e. Month 3) ]
   SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any= occurrence of SAE regardless of the relation to vaccination.
6. Number of subjects with any serious adverse events (SAEs) [ Time Frame: From 30 days post last vaccination (i.e. Month 3) to 1 year post last vaccination (i.e. Month 14) ]
   SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any= occurrence of SAE regardless of the relation to vaccination.
7. Number of subjects with any related SAEs [ Time Frame: During the entire study period (Visit day 1 to Month 26) ]
   SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Related= Any SAE related to investigational vaccine or related to study participation or to a GSK concomitant medication/vaccine as assessed by the investigator.
8. Number of subjects with any potential immune-mediated diseases (pIMDs). [ Time Frame: From Visit Day 1 up to 30 days post last vaccination (i.e. Month 3) ]
   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. Any= occurrence of pIMD regardless of intensity grade and relationship to the vaccination.
9. Number of subjects with any pIMDs. [ Time Frame: From 30 days post last vaccination (i.e. Month 3) to 1 year post last vaccination (i.e. Month 14) ]
   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. Any= occurrence of pIMD regardless of intensity grade and relationship to the vaccination
10. Vaccine response rate (VRR) for anti-glycoprotein E (Anti-gE) antibodies as determined by Enzyme Linked Immunosorbent Assay (ELISA) [ Time Frame: At Month 2 and Month 3 ]
    VRR is defined as percentage of subjects who have at least: - A 4-fold increase in the post last vaccination anti-gE Ab concentration as compared to the pre-vaccination anti-gE Ab concentration, for subjects who are seropositive at baseline, or, - A 4-fold increase in the post last vaccination anti-gE Ab concentration as compared to the anti-gE Ab cut-off value for seropositivity, for subjects who are seronegative at baseline.
11. Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs) as determined by ELISA [ Time Frame: At Day 1, Month 2 and Month 3 ]
    The geometric mean concentration (GMC) calculations are performed by taking the antilog of the mean of the log concentration transformations.

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subjects and/or subject's LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol
• Written informed consent obtained from the subject/subject's LAR(s) prior to performance of any study specific procedure.
• A male or female ≥ 50 YOA at the time of the first vaccination.

• Subjects with a history of HZ. Confirmation of the prior HZ diagnosis can be done by one of the following three methods:

  • Clinically diagnosed HZ:

OR Laboratory diagnosed HZ: OR

• HZ diagnosed by an adjudication committee: Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy, bilateral salpingectomy 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 for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Subjects who at time of study entry or during the maximum period of anticipated study participation are/will become part of the population recommended to receive a zoster vaccine per existing local or national immunization practices will be excluded from study participation.
• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Onset of HZ in the past 6 months or any ongoing symptoms from a prior HZ episode.
• Chronic antiviral use for HZ prophylaxis.
• History of >1 prior episode of HZ.
• A history of disseminated HZ, cutaneous or associated with visceral disease or associated with neurologic disease caused by VZV infection.
• Use or anticipated use of immunosuppressants or immune-modifying drugs during the period starting six months prior to study start and during the whole study period. This includes chronic administration of corticosteroids, long-acting immune-modifying agents or immunosuppressive/cytotoxic therapy
• Administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine. However, licensed pneumococcal vaccines and non-replicating vaccines may be administered up until 8 days prior to dose 1 and/or dose 2 and/or at least 14 days after any dose of study vaccine.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product
• Previous vaccination against VZV or HZ.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Acute disease and/or fever at the time of enrolment.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions in the period up to 2 months after completion of the vaccination series.

Contacts and Locations

Locations

Estonia

GSK Investigational Site

Tallinn, Estonia, 13619

GSK Investigational Site

Tartu, Estonia, 50106

Finland

GSK Investigational Site

Helsinki, Finland, 00180

GSK Investigational Site

Helsinki, Finland, 00290

GSK Investigational Site

Jyvaskyla, Finland, 40100

GSK Investigational Site

Kuopio, Finland, 70100

GSK Investigational Site

Tampere, Finland, FI-33100

GSK Investigational Site

Turku, Finland, 20100

Hong Kong

GSK Investigational Site

Hong Kong, Hong Kong, 000000

GSK Investigational Site

Shatin, Hong Kong, 000000

Mexico

GSK Investigational Site

Guadalajara, Jalisco, Mexico, 44657

GSK Investigational Site

Durango, Mexico, 34000

GSK Investigational Site

Mexico City, Mexico, 06760

GSK Investigational Site

Oaxaca, Mexico, 68000

Panama

GSK Investigational Site

Panama, Panama, 0801

GSK Investigational Site

Panama, Panama, 1001

Russian Federation

GSK Investigational Site

Barnaul, Russian Federation, 656043

GSK Investigational Site

Ekaterinburg, Russian Federation, 620137

GSK Investigational Site

Gatchina, Russian Federation, 188300

GSK Investigational Site

Moscow, Russian Federation, 115478

GSK Investigational Site

Saint Petersburg, Russian Federation, 197022

GSK Investigational Site

St.Petersburg, Russian Federation, 197089

Spain

GSK Investigational Site

Avila, Spain, 05071

GSK Investigational Site

Barcelona, Spain, 08023

GSK Investigational Site

Barcelona, Spain, 08025

GSK Investigational Site

Barcelona, Spain, 08028

GSK Investigational Site

Barcelona, Spain, 08035

GSK Investigational Site

Barcelona, Spain, 08036

GSK Investigational Site

Centelles (Barcelona), Spain, 08540

GSK Investigational Site

Hospitalet de Llobregat, Spain, 08907

GSK Investigational Site

La Roca Del Valles (Barcelona), Spain, 08430

GSK Investigational Site

Madrid, Spain, 28035

GSK Investigational Site

Madrid, Spain, 28040

GSK Investigational Site

Majadahonda( Madrid, Spain, 28222

GSK Investigational Site

Pama de Mallorca, Spain, 07010

GSK Investigational Site

Valencia, Spain, 46020

GSK Investigational Site

Vic/ Barcelona, Spain, 08500

United Kingdom

GSK Investigational Site

Poole, Dorset, United Kingdom, BH16 5PW

GSK Investigational Site

Addlestone, Surrey, United Kingdom, KT15 2BH

GSK Investigational Site

Atherstone, Warwickshire, United Kingdom, CV9 1EU

GSK Investigational Site

Bradford on Avon, Wiltshire, United Kingdom, BA15 1DQ

GSK Investigational Site

Trowbridge, Wiltshire, United Kingdom, BA14 8QA

GSK Investigational Site

Belfast, United Kingdom, BT7 2EB

GSK Investigational Site

Manchester, United Kingdom, M14 6WP

GSK Investigational Site

Nantwich, Cheshire, United Kingdom, CW5 5NX

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04091451
• Other Study ID Numbers: 204939; 2016-000744-34 ( EudraCT Number )
• First Posted: September 16, 2019
• Last Update Posted: May 9, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• 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.
• URL: https://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Shingles; Shingles recurrence; HZ; Vaccine response rate

Additional relevant MeSH terms:

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