Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 65 Years of Age With and Without Zostavax® Vaccination at Least 5 Years Earlier

• ClinicalTrials.gov Identifier: NCT02581410
• Recruitment Status: Completed
• First Posted: October 21, 2015
• Results First Posted: September 26, 2017
• Last Update Posted: August 28, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' HZ/su vaccine in adults ≥ 65 years of age with and without Zostavax® vaccination at least 5 years earlier.

Condition or disease	Intervention/treatment	Phase
Herpes Zoster	Biological: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A)	Phase 3

Detailed Description:

The study will evaluate two parallel groups of 200 adults ≥ 65 YOA; one group (Prev-Zvax) with a previous Zostavax® vaccination at least 5 years earlier, versus the other group without a previous Zostavax® vaccination (No prev-Zvax). The goal of this study is to generate immunogenicity, safety and reactogenicity data for the respective vaccines.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 430 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults ≥ 65 Years of Age With and Without Zostavax® Vaccination at Least 5 Years Earlier
• Actual Study Start Date: December 15, 2015
• Actual Primary Completion Date: August 30, 2016
• Actual Study Completion Date: August 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK1437173A Group; Subjects ≥ 65 years of age who received Zostavax vaccine ≥ 5 years earlier and received 2 doses of the HZ/su vaccine (first dose given at Month 0 and second dose given 2 months later) in this study.	Biological: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A); 2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.
Active Comparator: Control Group; Subjects ≥ 65 years of age who never received Zostavax vaccine and received 2 doses of the HZ/su vaccine (first dose given at Month 0 and second dose given 2 months later) in this study.	Biological: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A); 2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.

Outcome Measures

Primary Outcome Measures :

1. Anti-glycoprotein E (Anti-gE) Antibody (Ab) Concentrations [ Time Frame: One month after dose 2, at Month 3 ]
   Varicella Zoster Virus (VZV) gE Ab.Immunoglobulin G (IgG) was determined by Enzyme Linked Immunosorbent Assay (ELISA). Concentrations are presented as geometric mean concentrations (GMCs), expressed in milliinternational units per millilitre (mIU/mL). Geometric mean antibody concentrations were adjusted for group-matching variable.
2. Number of Subjects With Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) period after each dose. ]
   Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of the symptom regardless of its intensity grade. Grade 3 pain = Significant pain at rest that prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
3. Number of Days With Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) period after each dose. ]
   Solicited local symptoms were assessed during the 7-day (Days 0-6) period after each dose.
4. Number of Subjects With Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) period after each dose. ]
   Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhea and/or abdominal pain), headache, myalgia, shivering and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)] . Any = Occurrence of the symptom regardless of its 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.
5. Number of Days With Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) period after each dose. ]
   Solicited general symptoms were assessed during the 7-day (Days 0-6) period after each dose.
6. Number of Subjects With Any, Grade 3 and Related Unsolicited Symptoms (AEs) [ Time Frame: During the 30-day (Days 0-29) period after each dose. ]
   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.
7. Number of Subjects With Any and Related Serious Adverse Events (SAEs) [ Time Frame: From first vaccination (Month 0) up to 30 days post last vaccination (Month 3) ]
   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 related to the vaccination.
8. Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) [ Time Frame: From first vaccination (Month 0) up to 30 days post last vaccination (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.

Secondary Outcome Measures :

1. Anti-gE Ab Concentrations [ Time Frame: At Months 0, 1, 3 and 14. ]
   VZV gE IgG antibody concentrations were determined by ELISA. Concentrations are presented as geometric mean concentrations (GMCs), expressed in milliinternational units per millilitre (mIU/mL).
2. Frequencies of gE-specific Cluster of Differentiation 4 (CD4+) T-cells [ Time Frame: At Months 0, 1, 3 and 14. ]
   gE-specific CD4+ T-cells, expressing at least two activation markers (from among interferon gamma [IFN-γ], interleukin-2 [IL-2], tumour necrosis factor alpha [TNF-α] and cluster of differentiation 40-ligand [CD40L]), as determined by in vitro Intracellular Cytokine Staining (ICS).
3. Number of Subjects With Any and Related SAEs [ Time Frame: From 30 days post last vaccination (Month 3) until study end at Month 14 ]
   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 related to the vaccination.
4. Number of Subjects With Any pIMDs [ Time Frame: From 30 days post last vaccination (Month 3) until study end at 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.

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• A male or female ≥ 65 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to performing any study specific procedure.

For the No prev-Zvax group only:

• No previous vaccination with Zostavax.

For the Prev-Zvax group only:

• Previous vaccination with Zostavax ≥ 5 calendar years earlier.

• Documentation indicating the date of previous Zostavax vaccination will be required.

Exclusion Criteria:

• Previous vaccination with Zostavax < 5 calendar years earlier and/or anyone that ever received more than a single dose of Zostavax.
• Previous vaccination against VZV, administration of HZ/su vaccine or any other investigational or non-registered HZ vaccine (except Zostavax for the Prev-Zvax group).
• 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.
• Chronic administration (defined as > 14 consecutive days) of immunosuppressants or other immune-modifying drugs in the period starting 6 months prior to the first dose of vaccine. (For corticosteroids, a prednisone dose of < 20 mg/day, or equivalent, is allowed.) Inhaled, topical and intra-articular corticosteroids are allowed.
• Administration of long-acting immune-modifying drugs (e.g., infliximab) in the period starting 6 months prior to the first vaccine dose or expected administration at any time during the study period.
• 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 in the period starting 8 days prior to and ending 14 days after either dose of study vaccine.
• Current participation in or planned concurrent participation 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 product.
• Planned administration of an HZ vaccine (including an investigational or non-registered vaccine) other than the study vaccine during the entire study.
• History of HZ or any suspected HZ between the screening visit and Visit 1.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine/product.
• Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).

• Acute disease and/or fever at the time of enrolment.

  • Fever is defined as temperature ≥ 37.5°C (99.5°F) by oral route, axillary or tympanic setting, or ≥ 38.0°C/100.4°F on rectal setting. The recommended route for recording temperature in this study will be oral.
  • Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products in the period starting 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Significant underlying illness that, in the opinion of the investigator, would be expected to prevent completion of the study.
• Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
• Any condition which, in the judgment of the investigator, would make intramuscular (IM) injection unsafe.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Huntsville, Alabama, United States, 35802

United States, California

GSK Investigational Site

Daly City, California, United States, 94015

GSK Investigational Site

Los Gatos, California, United States, 95032

GSK Investigational Site

Oakland, California, United States, 94612

GSK Investigational Site

Roseville, California, United States, 95661

GSK Investigational Site

Santa Rosa, California, United States, 95405

United States, Idaho

GSK Investigational Site

Boise, Idaho, United States, 83642

United States, Kansas

GSK Investigational Site

Lenexa, Kansas, United States, 66219

GSK Investigational Site

Newton, Kansas, United States, 67114

GSK Investigational Site

Wichita, Kansas, United States, 67207

United States, Maine

GSK Investigational Site

Auburn, Maine, United States, 04210

United States, Maryland

GSK Investigational Site

Columbia, Maryland, United States, 21045

GSK Investigational Site

Elkridge, Maryland, United States, 21075

United States, Massachusetts

GSK Investigational Site

Marlborough, Massachusetts, United States, 01752

United States, New York

GSK Investigational Site

Binghamton, New York, United States, 13901

GSK Investigational Site

Endwell, New York, United States, 13760

United States, North Carolina

GSK Investigational Site

Charlotte, North Carolina, United States, 28209

United States, Ohio

GSK Investigational Site

Cleveland, Ohio, United States, 44122

United States, Oregon

GSK Investigational Site

Corvallis, Oregon, United States, 97330

United States, Pennsylvania

GSK Investigational Site

Erie, Pennsylvania, United States, 16506

GSK Investigational Site

Erie, Pennsylvania, United States, 16508

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19107

GSK Investigational Site

Uniontown, Pennsylvania, United States, 15401

United States, South Carolina

GSK Investigational Site

Mount Pleasant, South Carolina, United States, 29464

GSK Investigational Site

Spartanburg, South Carolina, United States, 29303

United States, Utah

GSK Investigational Site

Layton, Utah, United States, 84041

GSK Investigational Site

Salt Lake City, Utah, United States, 84109

GSK Investigational Site

Salt Lake City, Utah, United States, 84121

GSK Investigational Site

South Jordan, Utah, United States, 84095

United States, Virginia

GSK Investigational Site

Newport News, Virginia, United States, 23606

United States, Wisconsin

GSK Investigational Site

Eau Claire, Wisconsin, United States, 54701

GSK Investigational Site

Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Clinical Study Report 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 201198
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dagnew AF, Klein NP, Herve C, Kalema G, Di Paolo E, Peterson J, Salaun B, Schuind A. The Adjuvanted Recombinant Zoster Vaccine in Adults Aged >/=65 Years Previously Vaccinated With a Live-Attenuated Herpes Zoster Vaccine. J Infect Dis. 2021 Oct 13;224(7):1139-1146. doi: 10.1093/infdis/jiaa083.

Grupping K, Campora L, Douha M, Heineman TC, Klein NP, Lal H, Peterson J, Vastiau I, Oostvogels L. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine. J Infect Dis. 2017 Dec 12;216(11):1343-1351. doi: 10.1093/infdis/jix482.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02581410
• Other Study ID Numbers: 201198
• First Posted: October 21, 2015
• Results First Posted: September 26, 2017
• Last Update Posted: August 28, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

Zostavax®; ≥ 65 years of age; Herpes Zoster; Shingles; Immunogenicity; Safety

Additional relevant MeSH terms:

Herpes Simplex; Herpes Zoster; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Varicella Zoster Virus Infection