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

Study Overview
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Brief Summary
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The purpose of this study is 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.

Official Title
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A Phase IV, Randomized, Observer-blind, Placebo-controlled, Multi-center Study to Assess the Prophylactic Efficacy Against Herpes Zoster, Immunogenicity and Safety of Shingrix When Administered Intramuscularly on a 2-dose Schedule in Chinese Adults Aged 50 Years and Older

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: RZV
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 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 subject/subject'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 subjects as established by medical history and history-directed clinical examination before entering into the study. Female subjects 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 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 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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RZV Group<br>Participants randomized to the RZV Group receive 1 dose of RZV at Day 1 and 1 dose at Month 2 and are followed up until the study end. | Biological: RZV<br>* 2 doses of RZV in 0, 2 months schedule, administered intramuscularly in the deltoid region of the non-dominant arm<br>|
| Placebo Comparator: Placebo Group<br>Participants randomized to the Placebo Group receive 1 dose of placebo at Day 1 and 1 dose at Month 2 and are followed up until the study end. | Drug: Placebo<br>* 2 doses of placebo in 0, 2 months schedule, administered intramuscularly in the deltoid region of the non-dominant arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with confirmed HZ cases | A suspected case of HZ is defined as a new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A suspected case of HZ can be confirmed by PCR or by the HZ Ascertainment Committee. | From Month 3 (30 days after second vaccination) up to study end (approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with confirmed HZ cases, by age category (50-69 and ≥70 years of age) | A suspected case of HZ is defined as a new unilateral rash accompanied by pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. A suspected case of HZ can be confirmed by PCR or by the HZ Ascertainment Committee. | From Month 3 (30 days after second vaccination) up to study end (approximately 2 years) | 
| Percentage of participants with Any, Grade 3 (Grade 3 and above as per Chinese authorities) solicited local adverse events, resulting in a medically attended visit after each vaccination | The solicited administration site events are pain, redness and swelling. Any = occurrence of any solicited administration site event regardless of intensity grade. Grade 3 pain = pain that prevents normal activity. The maximum intensity of local injection site redness/swelling is scored at GSK using GSK's standard grading scale as follows: Grade 3 redness/swelling = redness/swelling above 100 millimeters (mm). The guidelines of grading standards set by the Chinese authorities are as follows: Grade 3 redness/swelling = redness/swelling above 100 mm and Grade 4 redness/swelling = Abscess, exfoliative dermatitis, and dermis or deep tissue necrosis. | From Day 1 to Day 7 after each vaccination | 
| Percentage of participants with Any, Grade 3 (Grade 3 and above as per Chinese authorities) resulting in a medically attended visit and relatedness (relationship to vaccination) of each solicited systemic event after each vaccination | The solicited systemic events are fatigue, fever, nausea, vomiting, diarrhea, abdominal pain, headache, myalgia and shivering. Fever is defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C) as per GSK guidelines and ≥37.3°C as per Chinese authorities' guidelines. Any = occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = general symptom that prevents normal activity. Grade 3 temperature = axillary temperature >39.0°C as per GSK guidelines and axillary temperature, 38.5°C - <39.5°C as per Chinese authorities' guidelines. Grade 4 temperature = axillary temperature ≥39.5°C as per Chinese authorities' guidelines. | From Day 1 to Day 7 after each vaccination | 
| Percentage of participants with Any, Grade 3, resulting in a medically-attended visit and relatedness (relationship to vaccination) of each unsolicited adverse events (AE) after each vaccination | Unsolicited AEs are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited AE. Any = occurrence of any unsolicited event regardless of intensity grade or relation to vaccination. Grade 3 symptom = event that prevents normal, everyday activities. Related = event assessed by the investigator as causally related to the study vaccination. | From Day 1 to Day 30 post vaccination period | 
| Percentage of participants with any and related SAEs from first vaccination up to 30 days post last vaccination | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient or results in abnormal pregnancy outcomes, or is considered medically significant. Any = Occurrence of an SAE, regardless of relationship to vaccination. Related = An SAE assessed by the investigator as causally related to the study vaccination. | From Day 1 up to 30 days post last vaccination | 
| Percentage of participants with any and related SAEs from first vaccination up to 12 months post last vaccination | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient or results in abnormal pregnancy outcomes, or is considered medically significant. Any = Occurrence of an SAE, regardless of relationship to vaccination. Related = An SAE assessed by the investigator as causally related to the study vaccination. | From Day 1 up to 12 months post last vaccination | 
| Percentage of participants with SAEs related to study vaccine from first vaccination up to study end | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient or results in abnormal pregnancy outcomes, or is considered medically significant. Related = An SAE assessed by the investigator as causally related to the study vaccination. | From Day 1 up to study end (approximately 2 years) | 
| Percentage of participants with SAEs related to study participation or to GlaxoSmithKline concomitant medication/vaccine during the entire study period | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient or results in abnormal pregnancy outcomes, or is considered medically significant. | From the time the subject consents to participate in the study (Day 1) until study end (approximately 2 years) | 
| Percentage of participants with any and related fatal SAEs from first vaccination up to 30 days post last vaccination | A fatal SAE refers to any SAE that led to death. Number and percentage of subjects experiencing fatal SAEs, classified by MedDRA Primary System Organ Class and Preferred Term are tabulated using date of onset of SAE for the time periods-from first vaccination up to 30 days post last vaccination and first vaccination up to 12 months post last vaccination and from study start up to study end will be presented with 95% CI. Fatal SAEs are also tabulated using the date of death within the same time periods. Any = Occurrence of a fatal SAE, regardless of relationship to vaccination. Related = A fatal SAE assessed by the investigator as causally related to the study vaccination. | From Day 1 up to 30 days post last vaccination | 
| Percentage of participants with any and related fatal SAEs from first vaccination up to 12 months post last vaccination | A fatal SAE refers to any SAE that led to death. Number and percentage of subjects experiencing fatal SAEs, classified by MedDRA Primary System Organ Class and Preferred Term are tabulated using date of onset of SAE for the time periods-from first vaccination up to 30 days post last vaccination and first vaccination up to 12 months post last vaccination and from study start up to study end will be presented with 95% CI. Fatal SAEs are also tabulated using the date of death within the same time periods. Any = Occurrence of a fatal SAE, regardless of relationship to vaccination. Related = A fatal SAE assessed by the investigator as causally related to the study vaccination. | From Day 1 up to 12 months post last vaccination | 
| Percentage of participants with related fatal SAEs from first vaccination up to study end | A fatal SAE refers to any SAE that led to death. Number and percentage of subjects experiencing fatal SAEs, classified by MedDRA Primary System Organ Class and Preferred Term are tabulated using date of onset of SAE for the time periods-from first vaccination up to 30 days post last vaccination and first vaccination up to 12 months post last vaccination and from study start up to study end will be presented with 95% CI. Fatal SAEs are also tabulated using the date of death within the same time periods. Related = A fatal SAE assessed by the investigator as causally related to the study vaccination. | From Day 1 up to end of study (approximately 2 years) | 
| Percentage of participants with any and related Potential immune-mediated diseases (pIMDs) from first vaccination up to 30 days post last vaccination. | PIMDs are a subset of AEs that includes autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. The investigator exercises his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin (i.e. pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. Any = Occurrence of a pIMD, regardless of relationship to vaccination. Related = A pIMD assessed by the investigator as causally related to the study vaccination. | From Day 1 up to 30 days post last vaccination | 
| The percentage of participants with any and related pIMDs from first vaccination up to 12 months post last vaccination. | PIMDs are a subset of AEs that includes autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. The investigator exercises his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin (i.e. pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. Any = Occurrence of a pIMD, regardless of relationship to vaccination. Related = A pIMD assessed by the investigator as causally related to the study vaccination. | From Day 1 up to 12 months post last vaccination | 
| Percentage of participants with related serious pIMDs after 12 months post last vaccination up to study end. | PIMDs are a subset of AEs that includes autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. The investigator exercises his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin (i.e. pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. Any = Occurrence of a pIMD, regardless of relationship to vaccination. Related = A pIMD assessed by the investigator as causally related to the study vaccination. | After 12 months post last vaccination up to study end (approximately 2 years). |