Study to Assess the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) When Co-administered With GSK Biologicals' Diphtheria, Tetanus and Pertussis Vaccine (Boostrix®) in Adults Aged 50 Years and Older

• ClinicalTrials.gov Identifier: NCT02052596
• Recruitment Status: Completed
• First Posted: February 3, 2014
• Results First Posted: April 24, 2018
• Last Update Posted: April 24, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study is to assess immunogenicity, reactogenicity and safety of GSK Biologicals' HZ/su vaccine when its first dose is co-administered with the Boostrix® vaccine in adults aged 50 years or older compared to administration of vaccines separately.

Condition or disease	Intervention/treatment	Phase
Herpes Zoster	Biological: Herpes Zoster vaccine GSK 1437173A; Biological: Boostrix	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 935 participants
• Allocation: 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 When Co-administered With Boostrix® in Adults Aged 50 Years and Older
• Actual Study Start Date: February 7, 2014
• Actual Primary Completion Date: June 16, 2015
• Actual Study Completion Date: April 21, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK1437173A Group; Subjects received one injection of Boostrix vaccine and one injection of the GSK1437173A vaccine during the first visit and a second injection of the GSK1437173A vaccine during the third visit, two months later.	Biological: Herpes Zoster vaccine GSK 1437173A; 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm at Visit Day 0 and Visit Month 2 for Co-Ad group and at Visit Month 2 and Visit Month 4 for Control group.; Biological: Boostrix; 1 dose administered intramuscularly (IM) in the deltoid region of the dominant arm at Visit Day 0 for both Co-Ad and Control groups.
Active Comparator: Control Group; Subjects received all vaccines separately i.e. one injection of Boostrix vaccine at the first visit, one injection of the GSK1437173A vaccine at the third visit and a second injection of the GSK1437173A vaccine at the fourth visit, all two months apart.	Biological: Herpes Zoster vaccine GSK 1437173A; 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm at Visit Day 0 and Visit Month 2 for Co-Ad group and at Visit Month 2 and Visit Month 4 for Control group.; Biological: Boostrix; 1 dose administered intramuscularly (IM) in the deltoid region of the dominant arm at Visit Day 0 for both Co-Ad and Control groups.

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With a Vaccine Response for Anti-glycoprotein E (Anti-gE) in GSK1437173A Group [ Time Frame: At 1 month post-Dose 2 (Month 3) ]

   This outcome was required only for the GSK1437173A Group. Vaccine response 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.

2. Antibody Concentrations Against Glycoprotein E (Anti-gE) [ Time Frame: At 1 month post-Dose 2 (Month 3 for GSK1437173A Group adn Month 5 for Control Group) ]
   Antibody concentrations against glycoprotein E (gE) have been assessed by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The reference seropositivity cut-off was an anti-gE antibody concentration greater than or equal to (≥) 97 mIU/mL.
3. Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) Antigens [ Time Frame: At 1 month post-Dose 1 (Month 1) ]
   Anti-PT, anti-FHA and anti-PRN antibody concentrations have been assessed by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).
4. Antibody Concentrations Against Diphteria (Anti-D) and Tetanus (Anti-T) Antigens [ Time Frame: At 1 month post-Dose 1 (Month 1) ]
   Anti-PT, anti-FHA and anti-PRN antibody concentrations have been assessed by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).

Secondary Outcome Measures :

1. Number of Subjects With Any and Grade 3 Solicited Local Symptoms, by Dose [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]

   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 activity. Grade 3 redness/swelling = redness/swelling spreading beyond (>) 100 millimeters (mm).

   "0" Implied that no data was applicable for the GSK1437173A Group at Dose 3, since it received only 2 vaccine doses

2. Number of Subjects With Any and Grade 3 Solicited Local Symptoms, by Study Vaccine [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]

   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 activity. Grade 3 redness/swelling = redness/swelling spreading beyond (>) 100 millimeters (mm).

   "0" implies that: 1. No data were applicable for the GSK1437173A vaccine at Dose 1 for the Control Group, as it was only administered at Doses 2 and 3 in this group 2. No data were applicable for the Boostrix vaccine at Doses 2 and 3 for any of the groups, as it was only administered at Dose 1 for both the groups.

   3. No data were applicable for the GSK1437173A Group at Dose 3, since it received only 2 vaccine doses.

3. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms, by Dose [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]

   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, rectal or tympanic temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = temperature above (>) 39.0 °C. Related = general symptom assessed by the investigator as causally related to vaccination.

   "0" Implied that no data was applicable for the GSK1437173A Group at Dose 3, since it received only 2 vaccine doses

4. Number of Days With Solicited Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]

   The number of days with local and general symptoms have been assessed during the solicited post-vaccination period.

   "0" Implied that no data was applicable for the GSK1437173A Group at Dose 3, since it received only 2 vaccine doses

5. Number of Subjects With Any and Related Potential Immune Mediated Diseases (pIMDs) [ Time Frame: From first vaccination up to study end (Day 0 to Month 14) ]
   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.
6. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: Within the 30-day (Days 0-29) post-vaccination period ]
   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 Serious Adverse Events (SAEs) [ Time Frame: From first vaccination up to study end (Day 0 to Month 14) ]
   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.

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 with the study vaccine(s).
• 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 2 months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent). A prednisone dose of < 20 mg/day is allowed. Inhaled, topical and intra-articular corticosteroids are allowed.
• 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(s) and ending 30 days after the last dose of study vaccine. This includes any type of vaccine such as (but not limited to) live, inactivated and subunit vaccines (e.g., inactivated and subunit influenza vaccines).
• 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.
• 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 (pharmaceutical product or device).
• Previous vaccination against VZV or HZ and/or planned administration during the study of an HZ or VZV vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
• History of HZ.
• Vaccination against diphtheria, or tetanus in the last five years or planned vaccination against diphtheria or tetanus during the study period, other than the study vaccine(s).
• Administration of a combined tetanus, diphtheria and pertussis (Tdap) vaccine at any time prior to study entry.
• 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).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines including prior severe allergic reaction following tetanus-toxoid, diphtheria-toxoid or pertussis-containing vaccine.
• Hypersensitivity to latex. Note: The investigational HZ/su vaccine does not contain latex.

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

  • Fever is defined as temperature ≥ 37.5°C /99.5°F by oral route. The preferred 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 within the 3 months preceding 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 before 2 months after the last dose of study vaccine.
• Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.
• Any condition which, in the judgment of the investigator, would make intramuscular (IM) injection unsafe.
• Encephalopathy (e.g. coma, decreased consciousness, prolonged seizures) not attributable to an identifiable cause within 7 days of administration of a previous pertussis antigen-containing vaccine.
• Progressive or unstable neurologic disorder.
• History of Arthus-type hypersensitivity reaction following a prior dose of a tetanus-toxoid containing vaccine within the last 10 years.
• History of Guillain-Barré syndrome within 6 weeks of receipt of a prior vaccine containing tetanus toxoid.

Contacts and Locations

Locations

United States, Arizona

GSK Investigational Site

Tucson, Arizona, United States, 85704

GSK Investigational Site

Tucson, Arizona, United States, 85712

United States, California

GSK Investigational Site

San Diego, California, United States, 92108

United States, Georgia

GSK Investigational Site

Stockbridge, Georgia, United States, 30281

United States, Idaho

GSK Investigational Site

Meridian, Idaho, United States, 83642

United States, Maine

GSK Investigational Site

Lewiston, Maine, United States, 04240

United States, Nevada

GSK Investigational Site

Las Vegas, Nevada, United States, 89104

United States, North Carolina

GSK Investigational Site

Charlotte, North Carolina, United States, 28209

GSK Investigational Site

Salisbury, North Carolina, United States, 28114

United States, Pennsylvania

GSK Investigational Site

Uniontown, Pennsylvania, United States, 15401

United States, Rhode Island

GSK Investigational Site

Warwick, Rhode Island, United States, 02886

United States, South Carolina

GSK Investigational Site

Greer, South Carolina, United States, 29650

United States, Virginia

GSK Investigational Site

Richmond, Virginia, United States, 23294

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

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

Strezova A, Lal H, Enweonye I, Campora L, Beukelaers P, Segall N, Heineman TC, Schuind AE, Oostvogels L. The adjuvanted recombinant zoster vaccine co-administered with a tetanus, diphtheria and pertussis vaccine in adults aged >/=50 years: A randomized trial. Vaccine. 2019 Sep 16;37(39):5877-5885. doi: 10.1016/j.vaccine.2019.08.001. Epub 2019 Aug 20.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02052596
• Other Study ID Numbers: 116887
• First Posted: February 3, 2014
• Results First Posted: April 24, 2018
• Last Update Posted: April 24, 2018
• Last Verified: September 2017

Keywords provided by GlaxoSmithKline:

Boostrix; Herpes zoster; Immunogenicity; Co-administration; Adults; 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