Safety and Immunogenicity of Different Dosing Schedules of GlaxoSmithkline (GSK) Biologicals' Herpes Zoster (HZ) Vaccine in Adults 50 Years of Age or Older

• ClinicalTrials.gov Identifier: NCT01751165
• Recruitment Status: Completed
• First Posted: December 17, 2012
• Results First Posted: March 31, 2017
• Last Update Posted: October 18, 2018
• 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 the GSK Biologicals' HZ vaccine 1437173A administered on either a 0,2-; 0,6- or 0,12-month schedule in adults aged 50 years or above, as the immunogenicity of the HZ vaccine administered at intervals longer than two months is not known.

Condition or disease	Intervention/treatment	Phase
Herpes Zoster	Biological: Herpes zoster vaccine GSK1437173A	Phase 3

Detailed Description:

Subjects in each group will be stratified by age with a minimum of 35 subjects in each stratum (50-59 years of age (YOA) stratum, 60-69 YOA stratum and ≥ 70 YOA stratum).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 354 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Open-label Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults Aged 50 Years or Older
• Study Start Date: March 12, 2013
• Actual Primary Completion Date: May 22, 2014
• Actual Study Completion Date: April 8, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: HZ/su-0,2 Group; Subjects will receive HZ/su vaccine on a 0,2-month schedule.	Biological: Herpes zoster vaccine GSK1437173A; 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.
Experimental: HZ/su-0,6 Group; Subjects will receive HZ/su vaccine on a 0,6-month schedule.	Biological: Herpes zoster vaccine GSK1437173A; 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.
Experimental: HZ/su-0,12 Group; Subjects will receive HZ/su vaccine on a 0,12-month schedule.	Biological: Herpes zoster vaccine GSK1437173A; 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Vaccine Response to Anti-glycoprotein E (Anti-gE) Antibodies as Determined by the Enzyme-linked Immunosorbent Assay (ELISA). [ Time Frame: At one month (M1) after Dose 2 ]

   Vaccine response was defined as: for initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/mL); for initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration.

   The objective required a comparison of VRR between 0,6-months and 0,12-months schedules.

2. Concentrations of Antibodies Against Anti-gE as Determined by ELISA. [ Time Frame: At one month (M1) after Dose 2 ]

Secondary Outcome Measures :

1. Concentrations of Antibodies Against Anti-gE as Determined by ELISA. [ Time Frame: Prior (PRE) to vaccination and twelve (M12) post Dose 2 ]
2. Number of Subjects With Solicited Local Symptoms. [ Time Frame: During the 7 day period (Days 0-6) following each dose (D) ]
   Solicited local symptoms assessed include pain, redness and swelling. "Grade 3 pain" was defined as crying when limb was moved/spontaneously painful. "Grade 3 swelling/redness" was defined as swelling/redness larger than (>) 100 millimeters (mm). "Any" is defined as incidence of the specified symptom regardless of intensity.
3. Number of Subjects With Solicited General Symptoms. [ Time Frame: During the 7 day period (Days 0-6) following each dose (D) ]
   Assessed solicited general symptoms were Fatigue, Gastrointestinal (meaning nausea, vomiting, diarrhoea and/or abdominal pain), Headache, Myalgia, Shivering and Temperature (temperature higher than [≥] 37.5 degrees Celsius [°C]). "Any" = occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. "Related" = occurrence of the specified symptom assessed by the investigators as causally related to vaccination. "Grade 3 Fatigue" = fatigue that prevented normal activity. "Grade 3 Gastrointestinal" = gastrointestinal that prevented normal every day activities. "Grade 3 Headache" = headache that prevented normal activity. "Grade 3 Myalgia" = myalgia that prevented normal activity. "Grade 3 Shivering" = shivering that prevented normal activity. "Grade 3 Temperature" = temperature higher than (>) 39.0°C.
4. Number of Subjects With Unsolicited Adverse Events (AEs). [ Time Frame: During the 30 Days (Day 0-29) following vaccination ]
   An adverse event (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.
5. Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: From first vaccination up to one month (30 Days) post last vaccination ]
   SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity.
6. Number of Subjects With SAE(s). [ Time Frame: Starting from 30 Days post last vaccine administration up to study end at Month 24 ]
   SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity.
7. Number of Days With Solicited Local Symptoms. [ Time Frame: During the 7 Days (Day 0-6) following vaccination ]
   Each dose was abbreviated as follows: D1 = Dose 1, D2 = Dose 2.
8. Number of Days With Solicited General Symptoms. [ Time Frame: During the 7 Days (Day 0-6) following vaccination ]
   Each dose was abbreviated as follows: D1 = Dose 1, D2 = Dose 2.
9. Number of Subjects With Potential Immune-mediated Diseases (pIMDs). [ Time Frame: From Dose 1 up to one month (30 days) following the last vaccine dose administration (Dose 2) ]
   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.
10. Number of Subjects With pIMDs. [ Time Frame: From one month (30 Days) following the last vaccine administration up to study end at Month 24 ]
    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: 50 Years and older (Adult, 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 aged 50 years or older at the time of the first vaccination.
• Written informed consent obtained from the subject.

• 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 two months after completion of the vaccination series.

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, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, a prednisone dose of < 20 mg/day, or equivalent, is allowed. Inhaled, topical and intra-articular corticosteroids are allowed.
• Administration or planned administration of a live vaccine in the period starting 30 days before and ending 30 days after either dose of study vaccine.
• Administration or planned administration of a non-replicating vaccine within eight days prior to or within 14 days after either dose of study vaccine.
• Administration of long-acting immune-modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period.
• Previous vaccination against varicella or HZ (either registered product or participation in a previous vaccine study).
• Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
• History of HZ.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
• 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) for oral, axillary or tympanic route, or ≥ 38.0°C (100.4°F) for rectal route. 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 be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products within the three 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.
• Pregnant or lactating female.
• Female planning to become pregnant during the entire treatment period and for two months after completion of the vaccination series, or planning to discontinue contraceptive precautions (if of childbearing potential).

Contacts and Locations

Locations

United States, California

GSK Investigational Site

Spring Valley, California, United States, 91978

United States, Kansas

GSK Investigational Site

Wichita, Kansas, United States, 67207

United States, Pennsylvania

GSK Investigational Site

Uniontown, Pennsylvania, United States, 15401

Estonia

GSK Investigational Site

Tartu, Estonia, 50106

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

IPD for this study will be made available via the Clinical Study Data Request site. 

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

Lal H, Poder A, Campora L, Geeraerts B, Oostvogels L, Vanden Abeele C, Heineman TC. Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study. Vaccine. 2018 Jan 2;36(1):148-154. doi: 10.1016/j.vaccine.2017.11.019. Epub 2017 Nov 22.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01751165
• Other Study ID Numbers: 116697; 2012-004456-11 ( EudraCT Number )
• First Posted: December 17, 2012
• Results First Posted: March 31, 2017
• Last Update Posted: October 18, 2018
• Last Verified: June 2018

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 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.
• URL: https://clinicalstudydatarequest.com

Keywords provided by GlaxoSmithKline:

≥ 50 years of age; Herpes zoster; Safety; Immunogenicity; Adults

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