Efficacy, Immunogenicity and Safety Study of GSKs Recombinant Zoster Vaccine Shingrix (GSK1437173A) in Chinese Adults Aged ≥50 Years

GlaxoSmithKline6,138 enrolled

Overview

The purpose of this study was to assess vaccine efficacy (VE), ability to generate immune response and safety of two doses of the recombinant subunit zoster vaccine (RZV) for prevention of Herpes Zoster (HZ) in Chinese adults aged 50 years and older.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

6,138

Conditions

Herpes Zoster

Interventions

RZVBIOLOGICAL

2 doses of RZV in 0, 2 months schedule, administered intramuscularly in the deltoid region of the non-dominant arm

PlaceboDRUG

2 doses of placebo in 0, 2 months schedule, administered intramuscularly in the deltoid region of the non-dominant arm

Eligibility

Sex: ALLMin age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. * Written or witnessed/thumb printed informed consent obtained from the participant/participant's LAR prior to performance of any study specific procedure. * A male or female aged 50 years or older at the time of the first vaccination. * Medically stable participants as established by medical history and history-directed clinical examination before entering into the study. * Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. * Female participants 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 * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series Exclusion Criteria: Medical conditions * Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study. * History of HZ. * Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study materials and equipment. * Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality as determined by physical examination or laboratory screening tests. * Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy. Prior/Concomitant therapy * Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period. * Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before each dose and ending 30 days after the last dose of vaccine administration. However, licensed pneumococcal vaccines and inactivated and subunit influenza vaccines (without adjuvant for seasonal or pandemic flu) may be co- administered with any dose of study vaccine. * Previous vaccination against varicella or HZ. * Administration of long-acting immune-modifying drugs at any time during the study period. * Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine up to one month post dose 2 (Month 3). * Planned or chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine. For corticosteroids, this will mean prednisone ≥20mg/day, or equivalent, is not allowed. Inhaled, intra-articular and topical steroids are allowed. Prior/Concurrent clinical study experience • 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. Other exclusions * Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months of last vaccination. * History of current/chronic alcohol consumption and/or drug abuse.

Locations (6)

GSK Investigational Site

Huaian, Jiangsu, China

GSK Investigational Site

Lianyungang, China

GSK Investigational Site

Shanghai, China

GSK Investigational Site

Shanghai, China

Outcomes

Primary Outcomes

Incidence Rate of Confirmed Herpes Zoster (HZ) Cases

A suspected case of HZ was defined as a new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A confirmed case of HZ was diagnosed by Polymerase Chain Reaction (PCR) or by the HZ Ascertainment Committee (HZAC) determination. The incidence rate (n/T) of confirmed HZ cases, expressed in terms of 1000 person-years rate, was calculated as the number of participants reporting at least one confirmed HZ case (n) in a group, over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 1000.

Time frame: From Month 3 (30 days after the second vaccination) up to study end (duration of approximately 2 years)

Secondary Outcomes

Incidence Rate of Confirmed HZ Cases, by Age Category

A suspected case of HZ was defined as a new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR or by the HZAC determination. The incidence rate (n/T) of confirmed HZ cases, expressed in terms of 1000 person-years rate, was calculated as the number of participants reporting at least one confirmed HZ case (n) in a group, over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 1000. The age categories assessed were 50-69 and greater than or equal to (\>=) 70 years of age (YOA).

Time frame: From Month 3 (30 days after the second vaccination) up to study end (duration of approximately 2 years)

Number of Participants With Any and at Least Grade 3 Solicited Local Adverse Events (AEs) (as Per GSK's Standard Grading Scale) and With Solicited Local AEs Resulting in a Medically Attended Visit

Assessed solicited local AEs included erythema, pain and swelling at injection site. The intensity of a solicited local AE was scored at GSK by using GSK's standard grading scale as follows: Any AE = occurrence of the event regardless of intensity grade. At least Grade 3 AE = occurrence of an at least Grade 3 or Grade 4 event (Grade 4 defined for some solicited AEs collected in the study as required by Chinese grading scale). Maximum of Grade 3 and 4 was considered as Grade 3 for all applicable solicited symptoms in GSK standard grading table. AE resulting in a medically attended visit = event for which the participant received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits.

Data from ClinicalTrials.gov

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GSK Investigational Site

Shanghai, China

Time frame: Within 7 days after each vaccination (occurring at Day 1 and Month 2)

Number of Participants With Any, at Least Grade 3 (as Per GSK's Standard Grading Scale) and Related Solicited General AEs and With Solicited General AEs Resulting in a Medically Attended Visit

Assessed solicited general AEs included fatigue, fever, gastrointestinal symptoms (nausea, vomiting and/or abdominal pain) headache, myalgia, and shivering. The intensity of a solicited general AE was scored at GSK by using GSK's standard grading scale as follows: Any AE = occurrence of the event regardless of intensity grade or relation to vaccination. At least Grade 3 AE = occurrence of an at least Grade 3 or Grade 4 event (Grade 4 defined for some solicited AEs collected in the study as required by Chinese grading scale). Maximum of Grade 3 and 4 was considered as Grade 3 for all applicable solicited symptoms in GSK standard grading table. Related AE = event assessed by the investigator as related to vaccination. AE resulting in a medically attended visit = event for which the participant received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits.

Time frame: Within 7 days after each vaccination (occurring at Day 1 and Month 2)

Number of Participants With at Least One Unsolicited AE, at Least One Grade 3 Unsolicited AE, at Least One Related Unsolicited AE, at Least One Grade 3 Related Unsolicited AE and With at Least One Medically Attended Unsolicited AE

An unsolicited AE was defined as any AE reported in addition to those solicited during the clinical study, or any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms. At least one unsolicited AE = at least one event regardless of intensity grade or relation to study vaccination. At least one Grade 3 unsolicited AE = at least one event that prevented normal, everyday activities. At least one related unsolicited AE = at least one event assessed by the investigator as related to the study vaccination. At least one Grade 3 related unsolicited AE = at least one event that prevented normal, everyday activities assessed by the investigator as related to the study vaccination. At least one medically attended unsolicited AE = at least one event for which the participant received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits.

Time frame: Within 30 days after any vaccination (occurring at Day 1 and Month 2)

Number of Participants With at Least One Serious Adverse Event (SAE) and With at Least One Related SAE From First Vaccination (Day 1) up to 30 Days Post Last Vaccination

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or was considered medically significant. At least one SAE = at least one SAE regardless of relation to study vaccination. At least one related SAE = at least one SAE assessed by the investigator as related to the study vaccination.

Time frame: From first vaccination (Day 1) up to 30 days post last vaccination (last vaccination administered at Day 1 for participants who received only 1 dose and at Month 2 for participants who received 2 doses)

Number of Participants With at Least One SAE and With at Least One Related SAE From First Vaccination (Day 1) up to 12 Months Post Last Vaccination

Time frame: From first vaccination (Day 1) up to 12 months post last vaccination (last vaccination administered at Day 1 for participants who received only 1 dose and at Month 2 for participants who received 2 doses)

Number of Participants With at Least One Related SAE From First Vaccination (Day 1) up to Study End (Duration of Approximately 2 Years)

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or was considered medically significant. At least one related SAE = at least one SAE assessed by the investigator as related to the study vaccination.

Time frame: From first vaccination (Day 1) up to study end (duration of approximately 2 years)

Number of Participants With at Least One SAE Related to Study Participation or to GlaxoSmithKline Concomitant Medication/Vaccine

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or was considered medically significant. SAEs related to study participation (and not to the study vaccine) or to GSK concomitant medication/vaccine were assessed.

Time frame: From the time the participant consented to participate in the study (Day 1) up to study end (duration of approximately 2 years)

Number of Participants With at Least One Fatal SAE and at Least One Related Fatal SAE From First Vaccination (Day 1) up to 30 Days Post Last Vaccination

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or was considered medically significant. At least one fatal SAE = at least one fatal SAE regardless of relation to study vaccination. At least one related fatal SAE = at least one fatal SAE assessed by the investigator as related to the study vaccination.

Number of Participants With at Least One Fatal SAE and With at Least One Related Fatal SAE From First Vaccination (Day 1) up to 12 Months Post Last Vaccination

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or was considered medically significant. At least one fatal SAE = at least one fatal SAE regardless of relation to study vaccination. At least one related fatal SAE = at least one fatal SAE assessed by the investigator as related to the study vaccination.

Number of Participants With at Least One Related Fatal SAE From First Vaccination (Day 1) up to Study End (Duration of Approximately 2 Years)

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or was considered medically significant. At least one related fatal SAE = at least one fatal SAE assessed by the investigator as related to the study vaccination.

Time frame: From first vaccination (Day 1) up to study end (duration of approximately 2 years)

Number of Participants With at Least One Potential Immune-mediated Disease (pIMD) and at Least One Related pIMD From First Vaccination (Day 1) up to 30 Days Post Last Vaccination

pIMDs were defined as a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune aetiology. At least one pIMD = at least one pIMD regardless of relation to vaccination. At least one related pIMD = at least one pIMD assessed by the investigator as related to the study vaccination.

Number of Participants With at Least One pIMD and at Least One Related pIMD From First Vaccination (Day 1) up to 12 Months Post Last Vaccination

pIMDs were defined as a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune aetiology. At least one pIMD = at least one pIMD regardless of relation to study vaccination. At least one related pIMD = at least one related pIMD assessed by the investigator as related to the study vaccination.

Number of Participants With at Least One Related Serious pIMD From 12 Months Post Last Vaccination up to Study End (Duration of Approximately 1 Year)

pIMDs were defined as a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune aetiology. At least one related serious pIMD = at least one serious pIMD assessed by the investigator as related to the study vaccination.

Time frame: From 12 months post last vaccination (last vaccination administered at Day 1 for participants who received only 1 dose and at Month 2 for participants who received 2 doses) up to study end (duration of approximately 1 year)