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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04091451

Collaborator

(none)

1,426

Enrollment

Locations

Arms

52.2

Anticipated Duration (Months)

32.4

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Sep 17, 2019

Anticipated Primary Completion Date :

Jan 22, 2024

Anticipated Study Completion Date :

Jan 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

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

Number of confirmed Herpes Zoster (HZ) cases [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

Number of confirmed HZ cases [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).
Number of subjects with any solicited local adverse events (AEs) [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.
Number of subjects with any solicited general adverse events (AEs) [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.
Number of subjects with any unsolicited AEs [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.
Number of subjects with any serious adverse events (SAEs) [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.
Number of subjects with any serious adverse events (SAEs) [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.
Number of subjects with any related SAEs [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.
Number of subjects with any potential immune-mediated diseases (pIMDs). [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.
Number of subjects with any pIMDs. [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
Vaccine response rate (VRR) for anti-glycoprotein E (Anti-gE) antibodies as determined by Enzyme Linked Immunosorbent Assay (ELISA) [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.
Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs) as determined by ELISA [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

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tallinn		Estonia	13619
2	GSK Investigational Site	Tartu		Estonia	50106
3	GSK Investigational Site	Helsinki		Finland	00180
4	GSK Investigational Site	Helsinki		Finland	00290
5	GSK Investigational Site	Jyvaskyla		Finland	40100
6	GSK Investigational Site	Kuopio		Finland	70100
7	GSK Investigational Site	Tampere		Finland	FI-33100
8	GSK Investigational Site	Turku		Finland	20100
9	GSK Investigational Site	Hong Kong		Hong Kong	000000
10	GSK Investigational Site	Shatin		Hong Kong	000000
11	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44657
12	GSK Investigational Site	Durango		Mexico	34000
13	GSK Investigational Site	Mexico City		Mexico	06760
14	GSK Investigational Site	Oaxaca		Mexico	68000
15	GSK Investigational Site	Panama		Panama	0801
16	GSK Investigational Site	Panama		Panama	1001
17	GSK Investigational Site	Barnaul		Russian Federation	656043
18	GSK Investigational Site	Ekaterinburg		Russian Federation	620137
19	GSK Investigational Site	Gatchina		Russian Federation	188300
20	GSK Investigational Site	Moscow		Russian Federation	115478
21	GSK Investigational Site	Saint Petersburg		Russian Federation	197022
22	GSK Investigational Site	Avila		Spain	05071
23	GSK Investigational Site	Barcelona		Spain	08023
24	GSK Investigational Site	Barcelona		Spain	08025
25	GSK Investigational Site	Barcelona		Spain	08028
26	GSK Investigational Site	Barcelona		Spain	08035
27	GSK Investigational Site	Barcelona		Spain	08036
28	GSK Investigational Site	Centelles (Barcelona)		Spain	08540
29	GSK Investigational Site	Hospitalet de Llobregat		Spain	08907
30	GSK Investigational Site	La Roca Del Valles (Barcelona)		Spain	08430
31	GSK Investigational Site	Madrid		Spain	28035
32	GSK Investigational Site	Madrid		Spain	28040
33	GSK Investigational Site	Majadahonda( Madrid		Spain	28222
34	GSK Investigational Site	Pama de Mallorca		Spain	07010
35	GSK Investigational Site	Valencia		Spain	46020
36	GSK Investigational Site	Vic/ Barcelona		Spain	08500
37	GSK Investigational Site	Poole	Dorset	United Kingdom	BH16 5PW
38	GSK Investigational Site	Addlestone	Surrey	United Kingdom	KT15 2BH
39	GSK Investigational Site	Atherstone	Warwickshire	United Kingdom	CV9 1EU
40	GSK Investigational Site	Bradford on Avon	Wiltshire	United Kingdom	BA15 1DQ
41	GSK Investigational Site	Trowbridge	Wiltshire	United Kingdom	BA14 8QA
42	GSK Investigational Site	Belfast		United Kingdom	BT7 2EB
43	GSK Investigational Site	Manchester		United Kingdom	M14 6WP
44	GSK Investigational Site	Nantwich, Cheshire		United Kingdom	CW5 5NX

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT04091451

Other Study ID Numbers:

204939
2016-000744-34

First Posted:

Sep 16, 2019

Last Update Posted:

Jul 25, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by GlaxoSmithKline

Shingles

Shingles recurrence

Vaccine response rate

Additional relevant MeSH terms:

Herpes Simplex

Herpes Zoster

Study Results

No Results Posted as of Jul 25, 2022