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Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A When Administered Subcutaneously Intramuscularly in Adults Aged ≥50 Years

Phase 3
Completed
Conditions
Herpes Zoster
Interventions
Biological: Herpes zoster vaccine GSK1437173A
Registration Number
NCT01777321
Lead Sponsor
GlaxoSmithKline
Brief Summary

The purpose of this study is to assess the immunogenicity, safety, and reactogenicity of GSK Biologicals' Herpes Zoster (HZ) vaccine (GSK 1437173A) when administered subcutaneously (SC) as compared to intramuscularly (IM) to people 50 years of age and older.

Detailed Description

There are 2 treatment groups in this study based upon the mode of vaccine administration.

The humoral immunogenicity (HI) will be measured in all subjects.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Subject who, in the opinion of the investigator, can and will comply with the requirements of the protocol.

  • Subject, residing in Japan, is of Japanese ethnic origin, defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese.

  • Subject has provided written informed consent.

  • Subject, male or female, who is 50 YOA or older at the time of the first vaccination.

  • Subject, if female, of non-childbearing potential may be enrolled in the study.

  • Subject, if female, 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 (i.e., for 2 months after Month 2).
Exclusion Criteria
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.

  • Concurrently participating or planned 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.

  • Administration or planned administration of a live vaccine within 30 days prior to the first study vaccination through 30 days after the second study vaccination.

  • Administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.

  • Planned administration, during the study, of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine.

  • Administration of immunoglobulins and/or any blood products within the three (3) months preceding the first dose of study vaccine or planned administration during the study period.

  • Chronic administration (defined as >14 consecutive days) 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 long-acting immune-modifying drugs (e.g., infliximab) within six months prior to the first vaccine dose through the duration of the study period.

  • History of HZ.

  • Previous vaccination against HZ or varicella (registered or investigational product).

  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study material and equipment.

  • 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.

  • Acute disease and/or fever at the time of vaccination:

    • 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.
  • Pregnant or lactating female.

  • Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) through Month 4 (i.e., 2 months after the second dose of study vaccine).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SC HZ/su GroupHerpes zoster vaccine GSK1437173ASubjects will receive HZ/su vaccine administered SC on a 0,2-month schedule.
IM HZ/su GroupHerpes zoster vaccine GSK1437173ASubjects will receive HZ/su vaccine administered IM on a 0,2-month schedule.
Primary Outcome Measures
NameTimeMethod
Number of Subjects With Anti-Glycoprotein E (Anti-gE) Antibody Concentrations Higher Than or Equal to (≥)18 Milli-international Units Per Milliliter (mIU/mL)Before vaccination (PRE), two months after Dose 1 (M2) and one month after Dose 2 (M3)

A seropositive subject was defined as a subject whose anti-gE Ab concentration was greater than or equal to the assay cut-off value, of 18 mIU/mL.

Anti-gE Antibody ConcentrationsBefore vaccination (PRE), two months after Dose 1 (M2) and one month after Dose 2 (M3)

Anti-gE antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in mIU/mL.

Number of Subjects With Vaccine Response for Anti-gE Antibody ConcentrationsAt two months after Dose 1 (M2) and one month after Dose 2 (M3)

Vaccine response was defined as: For initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x18 mIU/mL); for initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration.

Number of Subjects With Solicited Local SymptomsDuring the 7 day (Days 0-6) post vaccination, after each dose (D) and across doses

The solicited local symptoms assessed were: Arm movement/range of motion of the vaccinated arm, Injection site pruritus, Pain, Redness, and Swelling. Any = occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Significant pain at rest that prevented normal every day activities. Grade 3 Injection site pruritus = Significant pruritus that prevented normal every day activities. Grade 3 impairment of arm movement/range of motion = Significant impairment of arm movement/range of motion that prevented normal every day activities.

Descriptive Statistics of Anti-gE Antibody ConcentrationsBefore vaccination (PRE), at two months after dose 1 (M2) and one month after Dose 2 (M3)

Anti-gE antibody concentrations were assessed by the Enzyme Lynked Immunosorbent Assay.

Number of Subjects With Solicited General SymptomsDuring the 7 day (Days 0-6) post vaccination, after each dose (D) and across doses

Assessed solicited general symptoms were: Fatigue, Fever, Gastrointestinal (nausea, vomiting, diarrhea and/or abdominal pain), Headache, Myalgia, and Shivering. Fever = axillary temperature ≥37.5°C. Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 Fever = axillary temperature higher than (\>) 39.0°C. Related = general symptom assessed by the investigator as causally related to vaccination.

Mean Number of Days With Local SymptomsDuring the 7 day (Days 0-6) post vaccination, after each dose (D)

Days with solicited local symptoms were tabulated for the total vaccinated cohort.

Mean Number of Days With General SymptomsDuring the 7 day (Days 0-6) post vaccination, after each dose (D)

Days with solicited general symptoms were tabulated for the total vaccinated cohort.

Number of Subjects With Unsolicited Adverse Events (AEs)Within 30 days (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.

Number of Subjects With Potential Immune-Mediated Disorders (pIMDs)From Month 0 to Month 3

Potential immune-mediated diseases (pIMDs) were 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.

Number of Subjects With Serious Adverse Events (SAEs)From Month 0 to Month 3

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.

Secondary Outcome Measures
NameTimeMethod
Number of Subjects With Anti-gE Antibody Concentrations ≥ 97 mIU/mLAt Month 14

A seropositive subject was defined as a subject whose anti-gE Ab concentration was greater than or equal to the assay cut-off value of 97 mIU/mL.

Anti-gE Antibody ConcentrationsAt Month 14

Anti-gE antibody concentrations were expressed as geometric mean concnetrations (GMCs) and measured in mIU/mL.

Number of Subjects With Vaccine Response for Anti-gE Antibody ConcentrationsTwelve Months after Dose 2 (M14)

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.

Number of Subjects With pIMDsUp to Month 14 post vaccination period

Potential immune-mediated diseases (pIMDs) were 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.

Number of Subjects With SAEsUp to Month 14 post vaccination period

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.

Trial Locations

Locations (1)

GSK Investigational Site

🇯🇵

Fukuoka, Japan

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