Clinical trial NCT02979639: Study to Evaluate the Impact of Reactogenicity on Quality of Life (QoL), After Administration of GlaxoSmithKline (GSK) Biologicals' Candidate Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 50 Years of Age
Official title: Study to Evaluate the Impact of Reactogenicity on Quality of Life (QoL), After Administration of GSK Biologicals' Candidate Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 50 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Zoster
Keywords: Herpes Zoster
Reactogenicity
Quality of life
Shingles
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-12-01
Enrollment: 404
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the impact of reactogenicity of GSK Biologicals' HZ/su vaccine on Quality of Life (QoL) in adults ≥ 50 years of age

Detailed description: The study will evaluate the impact of HZ/su vaccination on the QoL, 400 adults ≥ 50 years of age (YOA). Subjects will be asked to respond to a series of SF-36 and EQ-5D questionnaires before and after vaccination following a 2 month schedule. To estimate the impact of reactogenicity on an individual's physical functioning (PF) and QoL, the study will compare subject questionnaire responses made during two periods, i.e., pre-vaccination and post-vaccination. The difference will be considered to be the effect of vaccination and reactogenicity on the PF and QoL. To characterize the study population and determine if frailty may influence reactogenicity and consequently the impact on QoL scores, the subjects' frailty status will be assessed at the first inclusion visit. In addition to the SF-36 and EQ-5D questionnaires, a more complete characterization of the reactogenicity of the vaccine will be made by including a detailed collection of the use of healthcare resources and the occurrence of symptoms through diary card data collection. Impact on days of work loss, both for the subject or for a caregiver, as applicable, will also be assessed.

Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. "Day 0" in the study design was replaced by "Day 1"; consequently, "Day n" was replaced by "Day n+1". Thus, the timeframes (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.

Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the questionnaires and diary cards).
* Written informed consent obtained from the subject prior to performance of any study specific procedure.
* A male or female aged ≥ 50 YOA at the time of consent.
* Female subjects of non-childbearing potential may be enrolled in the study.

  * For this study population, non-childbearing potential is defined as 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:

* Any condition which, in the judgment of the investigator, would make intramuscular (IM) injection unsafe.
* Use or planned use of any investigational or non-registered product (drug or vaccine) other than the study vaccine or current participation or planned concurrent participation in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device) during the period starting 30 days before the first dose of study vaccine and the study end.
* Use or anticipated use of immunosuppressants or other immune-modifying drugs during the period starting 180 days prior to study start and during the whole study period. This includes chronic administration of corticosteroids (\> 14 consecutive days of prednisone at a dose of ≥ 20 mg/day \[or equivalent\]), long-acting immune-modifying agents (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). Inhaled, topical and intra-articular corticosteroids are allowed.
* 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).
* Administration of immunoglobulins and/or any blood products in the period starting 90 days preceding the first dose of study vaccine or planned administration 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 15 days prior to and ending 14 days after either dose of study vaccine.
* Previous or planned administration of a vaccine against HZ (including an investigational or non-registered vaccine) other than the study vaccine, during the entire study period.
* History of HZ.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* Pregnant or lactating female.
* Significant underlying illness requiring medications that might confound the evaluation of general/ local AEs, or 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.

Primary outcomes:
measure: Change in the Short Form 36-item-health Survey (SF36) Physical Functioning (PF) From Baseline Score to Mean Score After First Dose
timeFrame: From Baseline at Day -7 to Day 8 after first dose
Secondary outcomes:
measure: Change in Mean SF-36 PF Scale Scores From Baseline Score to Mean Score After Second Dose
timeFrame: From Day -7 to first dose until Day 8 after second dose (equivalent to study Days -7 to 68)
measure: Change in Mean SF-36 PF Single Item Scores After First Dose
timeFrame: From Baseline at Day -7 to Day 8 after first dose
measure: Change in Mean SF-36 PF Single Item Scores After Second Dose
timeFrame: From Day -7 to first dose until Day 8 after second dose (equivalent to study Days -7 to 68)
measure: Change in SF-36 Role Physical Scores After First Dose
timeFrame: From Baseline at Day -7 to Day 8 after first dose
measure: Change in SF-36 Role Physical Scores After Second Dose
timeFrame: From Day -7 to first dose until Day 8 after second dose (equivalent to study Days -7 to 68)
measure: Change in Quality-adjusted Life Year (QALY) After First Dose
timeFrame: From Baseline at Day -7 to Day 8 after first dose
measure: Change in QALY After Second Dose
timeFrame: From Day -7 to first dose until Day 8 after second dose (equivalent to study Days -7 to 68)
measure: Number of Reactogenicity-triggered Medically Attended Visits After First Dose
timeFrame: From Day 1 to Day 7 after first dose
measure: Number of Reactogenicity-triggered Medically Attended Visits After Second Dose
timeFrame: From Day 1 to Day 7 after second dose
measure: Days of Work Loss for Subjects After First Dose
timeFrame: From Day 1 to Day 7 after first dose
measure: Days of Work Loss for Subjects After Second Dose
timeFrame: From Day 1 to Day 7 after second dose
measure: Days of Work Loss for Non-dedicated Caregivers After First Dose
timeFrame: From Day 1 to Day 7 after first dose
measure: Days of Work Loss for Non-dedicated Caregivers After Second Dose
timeFrame: From Day 1 to Day 7 after second dose
measure: Days of Extra Work for Dedicated Caregivers After First Dose
timeFrame: From Day 1 to Day 7 after first dose
measure: Days of Extra Work for Dedicated Caregivers After Second Dose
timeFrame: From Day 1 to Day 7 after second dose
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms After First Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after first dose.
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Second Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after second dose.
measure: Number of Days With Solicited Local Symptoms After First Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after first dose.
measure: Number of Days With Solicited Local Symptoms After Second Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after second dose.
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After First Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after first dose.
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Second Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after second dose.
measure: Number of Days With Solicited General Symptoms After First Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after first dose.
measure: Number of Days With Solicited General Symptoms After Second Dose
timeFrame: During a 7-day follow-up period (Day 1 to Day 7) after second dose.
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During a 30-day follow-up period (Day 1 to Day 30) after any vaccination (across doses).
measure: Number of Subjects With Any and Related Serious Adverse Events (SAEs) During the Entire Study Period
timeFrame: From Day 1 to study end at Month 14
measure: Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs)
timeFrame: From Day 1 to study end at Month 14
Other outcomes:
Locations:
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Meridian
country: United States
facility: GSK Investigational Site
state: Idaho
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Corvallis
country: United States
facility: GSK Investigational Site
state: Oregon
city: Uniontown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Schmader KE, Levin MJ, Grupping K, Matthews S, Butuk D, Chen M, Idrissi ME, Fissette LA, Fogarty C, Hartley P, Klein NP, Nevarez M, Uusinarkaus K, Oostvogels L, Curran D. The Impact of Reactogenicity After the First Dose of Recombinant Zoster Vaccine on the Physical Functioning and Quality of Life of Older Adults: An Open-Label, Phase III Trial. J Gerontol A Biol Sci Med Sci. 2019 Jul 12;74(8):1217-1224. doi: 10.1093/gerona/gly218.