A Study to Assess Frailty of Subjects During ZOSTER-006 and ZOSTER-022

Herpes Zoster Clinical Trial

Official title:

Observational Study to Assess Frailty of Subjects During ZOSTER-006 and ZOSTER-022 and HZ Efficacy, Immunogenicity and Safety of HZ/su by Frailty Status

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03563183
• Other study ID #: 204878
• Status: Completed
• Start date: June 5, 2018
• Est. completion date: April 30, 2019

Study information

• Verified date: April 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

As part of the ZOSTER-006 and ZOSTER-022 pivotal trials of the HZ/su vaccine, all study participants completed quality of life (QoL) questionnaires. The only questionnaires encoded into the data base were those from participants who developed a suspected shingles episode during the study.

The purpose of this study is to allow for the encoding and analysis of questionnaires for all subjects enrolled in ZOSTER-006 and ZOSTER-022. The aim is to assess the baseline frailty of subjects enrolled in these studies and to investigate whether this population is representative of the general population.

Description:

As part of the study procedure, each subject enrolled in studies Zoster-006 and Zoster-022 was asked to complete two quality of life (QoL) questionnaires named respectively SF-36 and EQ-5D at predefined study time points. These questionnaires were to provide relevant information about the quality of life (functional status, ability to socialize, mental health, etc.) of subjects before they develop shingles Extracting some elements of the Quality of Life questionnaires (QoL), EQ-5D and SF-36, completed by all study subjects at baseline, and combining them with other medical history data allows attributing of frailty scores.

Analyses pertaining to efficacy, safety and immunogenicity as per frailty score might be performed according to the methodology used in the ZOSTER-006 and ZOSTER-022 studies.

Additionally, the data collected can be used to assess if some physical, physiological and/or psychological characteristics reported by the subjects before the onset of HZ would be predictive of HZ.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26976
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• All subjects who participated in the Zoster 006 and Zoster 022 trials.

• Subjects who died or were lost to follow-up during ZOSTER-006 and ZOSTER-022 will be considered for enrolment in ZOSTER-064 and their data/questionnaires up to that point will be used.

Exclusion Criteria:

• Subjects who were excluded from all analyses from ZOSTER-006 and ZOSTER-022. This will include any subject eliminated following deviations from GCP compliance.

• Subjects who developed a suspected HZ case during ZOSTER-006 and ZOSTER-022 (since their QoL questionnaires were encoded in the eCRF for ZOSTER-006 and ZOSTER-022).

Related Conditions & MeSH terms

• Frailty
• Herpes Zoster

Intervention

Other:
• Encoding of data collected in Zoster 006 and Zoster 022 studies
Not applicable (disease epidemiology study)

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Maroubra	New South Wales
Australia	GSK Investigational Site	Sherwood	Queensland
Australia	GSK Investigational Site	Umina	New South Wales
Australia	GSK Investigational Site	Westmead	New South Wales
Australia	GSK Investigational Site	Wollongong	New South Wales
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Curitiba/PR
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Bay Roberts	Newfoundland and Labrador
Canada	GSK Investigational Site	Gatineau	Quebec
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Mirabel	Quebec
Canada	GSK Investigational Site	Pointe-Claire	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Québec City	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Victoria	British Columbia
Canada	GSK Investigational Site	Woodstock	Ontario
Czechia	GSK Investigational Site	Hradec Kralove
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Finland	GSK Investigational Site	Tampereen Yliopisto
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Château Gontier
France	GSK Investigational Site	Cherbourg
France	GSK Investigational Site	Clermont-Ferrand
France	GSK Investigational Site	Laval
France	GSK Investigational Site	Montrevault
France	GSK Investigational Site	Muret
France	GSK Investigational Site	Murs-Erigne
France	GSK Investigational Site	Nantes cedex 2
France	GSK Investigational Site	Rosiers-d'Egletons
France	GSK Investigational Site	Saint Cyr sur Loire
France	GSK Investigational Site	Segré
France	GSK Investigational Site	Tours
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dachau	Bayern
Germany	GSK Investigational Site	Deggingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Duelmen	Niedersachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Floersheim	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Freiberg	Sachsen
Germany	GSK Investigational Site	Goch	Nordrhein-Westfalen
Germany	GSK Investigational Site	Gueglingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kuenzing	Bayern
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Magdeburg
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Pirna	Sachsen
Germany	GSK Investigational Site	Rednitzhembach	Bayern
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wallerfing	Bayern
Germany	GSK Investigational Site	Wangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Weinheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wuerzburg	Bayern
Hong Kong	GSK Investigational Site	Kwun Tong
Hong Kong	GSK Investigational Site	Shatin
Italy	GSK Investigational Site	Chieti	Abruzzo
Italy	GSK Investigational Site	Cuneo	Piemonte
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Monza	Lombardia
Italy	GSK Investigational Site	Pescara	Abruzzo
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Gangwon-do
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Zapopan, Jalisco	Jalisco
Spain	GSK Investigational Site	Alcover( Tarragona)
Spain	GSK Investigational Site	Balenyà (Barcelona)
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Centelles (Barcelona)
Spain	GSK Investigational Site	La Roca Del Valles (Barcelona)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda( Madrid
Spain	GSK Investigational Site	Marid
Spain	GSK Investigational Site	Peralada( Girona)
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vic/ Barcelona
Sweden	GSK Investigational Site	Borås
Sweden	GSK Investigational Site	Eskilstuna
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Jönköping
Sweden	GSK Investigational Site	Karlskrona
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Uppsala
Sweden	GSK Investigational Site	Vällingby
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taoyuan County
United Kingdom	GSK Investigational Site	Atherstone	Warwickshire
United Kingdom	GSK Investigational Site	Bangor
United Kingdom	GSK Investigational Site	Belfast
United Kingdom	GSK Investigational Site	Bradford on Avon	Wiltshire
United Kingdom	GSK Investigational Site	Broughshane
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	Newtonabbey
United States	GSK Investigational Site	Beachwood	Ohio
United States	GSK Investigational Site	Bristol	Tennessee
United States	GSK Investigational Site	Cary	North Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Greer	South Carolina
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Meridian	Idaho
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Mount Pleasant	North Carolina
United States	GSK Investigational Site	Murray	Utah
United States	GSK Investigational Site	Newport News	Virginia
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pleasant Hills	Pennsylvania
United States	GSK Investigational Site	Renton	Washington
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Salisbury	North Carolina
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Spring Valley	California
United States	GSK Investigational Site	Uniontown	Pennsylvania
United States	GSK Investigational Site	Wadsworth	Ohio
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winchester	Virginia
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Mexico,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects by Frailty Status, at Baseline	Frailty status was measured in relation to the accumulation of deficits using a Frailty Index (FI) adapted from the model proposed by Mitnitski et al. [Mitnitski, 2001]. The different aspects of frailty composing the FI were assessed through the medical history and components of the Short Form 36 Questionnaire (SF-36) and EuroQol (EQ)-5D questionnaires recorded pre-vaccination Dose 1 (in the study ZOSTER-006[NCT01165177] and ZOSTER-022[NCT01165229]).; If the FI was less than or equal to 0.08, the subject was classified as Non-Frail. If the score was greater than 0.08 but less than or equal to 0.25, the subject was classified as pre-frail. If the score was greater than 0.25, the subject was classified as Frail. Subjects without a FI score were classified as unknown.	At Baseline (Month 0)
Secondary	Distribution of Short Form 36 (SF-36) Questionnaire Scale Scores, by Country	The mean and standard deviation of the SF-36 Questionnaire scale scores are presented for each time point. The SF-36 is a multi-purpose health survey with 36 questions underlying the construction of 8 scales [Ware, 2001]: Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE) and Mental Health (MH).; All but one of the 36 items (self-reported health transition) are used to score the eight SF-36 scales. Each item is used in scoring only one scale. Scale scores are constructed following the summated ratings and standardized SF-36 scoring algorithms. The SF-36 scores range from 0 to 100, with high scores indicating high levels of functioning/quality of life.	At Month 0, 14, 26 and 38
Secondary	Distribution of EuroQol (EQ)-5D Questionnaire Scale Scores, by Country	The EQ-5D questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 possible responses (No symptoms, Moderate symptoms, Extreme symptoms). The 5 items are then combined to generate health profiles that are subsequently converted to a continuous single index utility score using a one to one matching. Country or region-specific value sets are used for the score conversion. The scores range from less than 0 (where 0 is the value of a health state equivalent to dead) to 1 (the value of full health), with higher scores indicating higher health utility.; The EQ-5D also contains a visual analogue scale (VAS). The VAS records the respondent's self-rated health on a vertical scale, ranging from 0(worst imaginable health state) to 100(best imaginable health state).	At Month 0, 14, 26 and 38
Secondary	Incidence Rate (Per 1000 Person-years) of Confirmed Herpes Zoster (HZ) Cases, by Frailty Status	Incidence rate (IR) of confirmed Herpes zoster (HZ) cases with 95% Confidence Interval (CI) calculated as the number of cases per 1000 person-years : numerator = number of confirmed HZ cases reported during the follow-up (FU) period at risk; denominator = total Person-years at risk, i.e. sum of FU periods at risk expressed in years until first confirmed HZ cases or occurrence of treatment for relapse. A suspected HZ case defined as (1) new rash characteristic of HZ (e.g., unilateral, dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or other sensations), or vesicular rash suggestive of Varicella Zoster Virus (VZV) infection regardless of the distribution, and no alternative diagnosis; or (2) clinical presentation and specific laboratory findings suggestive of VZV infection in the absence of HZ or VZV rash. A suspected case of HZ was confirmed either by PCR or by the HZ Ascertainment Committee (HZAC), consisting of physicians with HZ expertise.	During the entire study period (3 to 5 year period following Day 0)
Secondary	Herpes Zoster Burden of Illness Score, by Frailty Status	Zoster Brief Pain Inventory (ZBPI) Burden of Illness (BOI) score was calculated as the sum of the ZBPI worst pain scores for all subjects in the group divided by the total follow-up time (Person-years). HZ Burden of Illness score for subjects was calculated from the Zoster Brief Pain Inventory (ZBPI), for each confirmed HZ cases responding to the "worst pain" question in both ZOSTER-006 and ZOSTER-022, and defined as the area under the curve of confirmed HZ-associated pain plotted against time during the 182-day period after the onset of the case. Subjects who developed HZ presented "burden-of-illness" scores ranging from 0 up to, theoretically, 1820. A score of 0 is recorded for subjects in whom HZ did not develop during the study period. Subjects who had a confirmed Zoster episode but who did not have at least 1 ZBPI assessment were excluded from the analysis.	During the entire study period (3 to 5 year period following Day 0)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms, by Frailty Status	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) of injection site.	Within 7 days (Days 0-6) after each vaccination
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms, by Frailty Status	Assessed solicited general symptoms were, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and gastro-intestinal (GI) symptoms(nausea, vomiting, diarrhoea and/or abdominal pain) Any = occurrence of the symptom regardless of 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.	Within 7 days (Days 0-6) after each vaccination
Secondary	Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs), by Frailty Status	An unsolicited AE covered 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.	Within 30 days (Days 0 - 29) after each vaccination
Secondary	Number of Subjects With Any and Related Serious Adverse Events (SAEs), by Frailty Status	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. Related SAEs were those considered vaccine-related by the investigator.	From Month 0 to Month 14
Secondary	Number of Subjects With SAEs Related to Study Participation or to a Concurrent GSK Medication/Vaccine, by Frailty Status	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. Related SAEs throughout the entire study period by frailty status were reported for SAEs considered related to study participation or to a concurrent GSK medication/vaccine.	During the entire study period (3 to 5 year period following Day 0)
Secondary	Number of Subjects With Any Fatal Serious Adverse Events (SAEs), by Frailty Status	Serious adverse events (SAEs) assessed include medical occurrences that result in death.	During the entire study period (3 to 5 year period following Day 0)
Secondary	Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs), by Frailty Status	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 related to the vaccination.	During the entire study period (3 to 5 year period following Day 0)
Secondary	Anti-glycoprotein E (Anti-gE) Antibody (Ab) Concentrations, by Frailty Status, in a Subset of Subjects	Anti-gE Ab concentrations as determined by Enzyme-linked Immunosorbent Assay (ELISA), in a subset of subjects. The assay cut-off is 97 milli-international units (mIU)/mL.	Pre-vaccination at Month 0, and post second dose at Months 3, 14, 26 and 38
Secondary	Anti-Varicella Zoster Virus (Anti-VZV) Antibody (Ab) Concentrations, by Frailty Status, in a Subset of Subjects	Anti-VZV Ab concentrations as determined by Enzyme-linked Immunosorbent Assay (ELISA), in a subset of subjects. The assay cut-off is 25 mIU/mL.	Pre-vaccination at Month 0, and post second dose at Months 3, 14, 26 and 38