A Study on the Immune Response and Safety of a Vaccine Against Herpes Zoster in Adults Aged 50 Years and Older in India

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the humoral immunogenicity and safety of 2 doses of GSK Biologicals' Herpes Zoster subunit vaccine (HZ/su) administered for the prevention of Herpes Zoster (HZ) in adults aged 50 years of age (YOA) or older from India.

Official Title
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A Phase 3, Randomised, Observer-blind, Placebo-controlled, Multi-centre Study to Evaluate the Immune Response and Safety of the Herpes Zoster Subunit Vaccine When Administered Intramuscularly on a 2-dose Schedule in Adults Aged 50 Years and Older in India

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: HZ/su
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants and/or participant's legally acceptable representative(s) (LAR) 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 and/or participant's LAR(s) after the study has been explained according to local regulatory requirements and prior to performance of any study-specific procedure. A male or female aged 50 YOA or older at the time of the first study intervention. Healthy participants or medically stable patients as established by medical history and clinical examination before entering into the study. Female participants of non-childbearing potential may be enrolled in the study. Female participants of childbearing potential may be enrolled in the study, if the participant: has practiced adequate contraception for 1 month prior to study intervention administration, and has a negative pregnancy test on the day of study intervention administration, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study intervention administration series. Exclusion Criteria: Medical conditions Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s) vaccine or study materials or equipment. Acute or chronic 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, based on medical history and physical examination (no laboratory testing required). History of HZ. Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. Prior/Concomitant therapy • Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before first dose and ending 30 days after the last dose of study intervention administration with the exception of licensed pneumococcal vaccines and non-replicating vaccines may be administered up until 8 days prior to Dose 1 and/or Dose 2 and/or at least 14 days after any dose of study intervention. [In case an emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is recommended and/or organised by the public health authorities, outside the routine immunisation programme, the time period described above can be reduced if necessary for that vaccine provided it is used according to local governmental recommendations and that the Sponsor is notified accordingly.] Planned 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 intervention up to 1 month post-dose 2 (Month 3) or planned administration during the study period. 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 equivalent ≥ 20 mg/day or equivalent is not allowed. Inhaled, intra-articular and topical steroids are allowed. Previous vaccination against varicella or HZ. Prior/Concurrent clinical study experience Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/ invasive medical device). Other exclusions Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months of last study intervention administration. Indications of drug abuse or excess alcohol use as deemed by investigator to potentially confound safety assessments or render participant unable or unlikely to adhere to protocol requirements.

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: HZ/su Group<br>Participants randomized to the HZ/su Group receive two doses of the HZ/su vaccine. | Biological: HZ/su<br>* Two doses of the HZ/su vaccine administered intramuscularly, one each at Day 1 and Month 2.<br>|
| Placebo Comparator: Placebo Group<br>Participants randomized to the Placebo Group receive two doses of Placebo. | Drug: Placebo<br>* Two doses of Placebo (lyophilised sucrose reconstituted with saline [NaCl] solution) administered intramuscularly, one each at Day 1 and Month 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants showing a vaccine response for anti-glycoprotein E (gE) | A participant with vaccine response for anti-gE is defined as a participant with: a 4-fold increase in the post-last vaccination anti-gE antibody (Ab) concentration as compared to the pre-vaccination anti-gE Ab concentration, for participants who are seropositive at baseline, or a 4-fold increase in the post-last vaccination anti-gE Ab concentration as compared to the anti-gE Ab cut-off value for seropositivity, for participants who are seronegative at baseline. | At 1 month post-dose 2 of study intervention administration (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-gE antibody concentrations expressed as geometric mean concentrations (GMCs) and between-group GMC ratios |  | At 1 month post-dose 2 of study intervention administration (Month 3) | 
| Percentage of participants reporting solicited administration site events | The solicited administration site events include injection site pain, redness, swelling and pruritis. | Within 7 days after each study intervention dose and across doses (vaccine/placebo administered at Day 1 and Month 2) | 
| Percentage of participants reporting solicited systemic events | The solicited systemic events include fatigue, fever, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and shivering. | Within 7 days after each study intervention dose and across doses (vaccine/placebo administered at Day 1 and Month 2) | 
| Percentage of participants reporting unsolicited adverse events (AEs) | An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. | Within 30 days after any study intervention dose administration (vaccine/placebo administered at Day 1 and Month 2) | 
| Percentage of participants reporting serious adverse events (SAEs) | 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 participant or an abnormal pregnancy outcome, or an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes. | From Day 1 up to Month 3 | 
| Percentage of participants reporting potential immune-mediated diseases (pIMDs) | pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 up to Month 3 | 
| Percentage of participants reporting SAEs | 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 participant or an abnormal pregnancy outcome, or an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes. | From Day 1 up to study end (Month 8) | 
| Percentage of participants reporting pIMDs | pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. | From Day 1 up to study end (Month 8) | 
| Anti-gE antibody concentrations expressed as GMCs |  | At pre-study intervention administration (Day 1) and at 1 month post-dose 2 of study intervention administration (Month 3) | 
| Percentage of participants seropositive for anti-gE antibodies | A participant seropositive for anti-gE antibodies is defined as a participant whose antibody concentration is greater than or equal to the assay cut-off value (97 mIU/mL). | At pre-study intervention administration (Day 1) and at 1 month post-dose 2 of study intervention administration (Month 3) | 
| Mean geometric increase (MGI) of anti-gE antibody concentrations | MGI is defined as the geometric mean of the within participant ratios of anti-gE antibody concentration at 1 month post-dose 2 (Month 3) compared to pre-study intervention administration (Day 1) anti-gE antibody concentration. | At 1 month post-dose 2 of study intervention administration (Month 3) compared to pre-study intervention administration (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Shingles, Herpes Zoster subunit vaccine, Immunogenicity, Adults aged 50 years and older, India