The purpose of the sutdy is to evaluate efficacy, safety and immunogenicity of Recombinant Zoster Vaccine (CHO Cell) with 2 doses at 2-month interval in adults aged 40 years and older.
A total of 25000 adults aged 40 years and older will be enrolled, stratified into 40-49, 50-59, 60-69 and ≥70 years of age. All subjects will randomly receive investigational vaccine or placebo at a ratio of 1:1. Efficacy and safety will be assessed in all subjects, while immunogenicity will be assessed in a subset of 1250 subjests in a selected trial site.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
25,000
0.5 mL per dose, containing a total of 50 µg recombinant varicella zoster virus glycoprotein E, adjuvanted with MA105. Intramuscular injection
0.5 mL per dose, containing 4.5 mg sodium chloride. Intramuscular injection
Hebei Provincial Center for Disease Control and Prevention
Shijiazhuang, Hebei, China
Henan Center for Diseases Control and Prevention
Zhengzhou, Henan, China
Hubei Provincial Center for Disease Control and Prevention
Wuhan, Hubei, China
Yunnan Center For Disease Control and Prevention
Kunming, Yunnan, China
Incidence of confirmed Herpes Zoster(HZ) Cases per person years in subjects aged 40 years and older
A suspected case of HZ was confirmed either: by Polymerase Chain Reaction (PCR) or by the Endpoint Adjudication Committee (EAC), consisting of physicians with HZ expertise.
Time frame: 30 days after the last vaccination
Incidence of confirmed Herpes Zoster(HZ) Cases per person years in different age group.
All subjects will be stratified into 40-49 years, 50-59 years, 60-69 years and ≥70 years of age.
Time frame: 30 days after the last vaccination
Incidence of any and severe Postherpetic Neuralgia (PHN) cases per person years in subjects aged 40 years and older, 40-49years , 50-59 years , 60-69 years and ≥70 years , with confirmed HZ.
PHN of any severity was defined as 0 and greater on the Zoster Brief Pain Inventory(ZBPI) questionnaire, while severe PHN rated as 3 and greater on the ZBPI questionnaire.
Time frame: 30 days after the last vaccination
Geometric Mean Concentration(GMC) of anti-gE antibody and anti-VZV antibody in immunogenicity subset
Measured by ELISA
Time frame: At 1, 12, 24 and 36 months after the last vaccination
Seropositivity rate of anti-gE antibody and anti-VZV antibody in immunogenicity subset
The seropositivity rate is defined as the percentage of subjects whose antibody concentration is greater than or equal to the cut-off value.
Time frame: At 1, 12, 24 and 36 months after the last vaccination
Seroresponse rate of anti-gE antibody and anti-VZV antibody in immunogenicity subset
The seroresponse rate is defined as the percentage of subjects who have at least a: 4-fold increase in the antibody concentration as compared to the pre vaccination antibody concentration, for subjects who are seropositive at baseline, OR, 4-fold increase in the antibody concentration as compared to the antibody concentration cut-off value for seropositivity, for subjects who are seronegative at baseline.
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Time frame: 30 days after the last vaccination
Geometric Mean Fold Rise (GMFR) of anti-gE antibody and anti-VZV antibody in immunogenicity subset
The antibody concentration at evaluted time points compared with that at baseline.
Time frame: At 1, 12, 24 and 36 months after the last vaccination
Four-fold increase rate of anti-gE antibody and anti-VZV antibody in immunogenicity subset
The antibody concentration 30 days after the last vaccination compared with that at baseline.
Time frame: 30 days after the last vaccination
Cell-Mediated Immunity (CMI) response
CMI response is defined as the frequency of CD4+ T cells producing at least 2 activation markers (IFN-γ, IL-2, TNF-α and/or CD40L) upon in vitro stimulation by gE peptide pools.
Time frame: 30 days after the last vaccination
Vaccine Response Rate (VRR)
VRR is defined as the percentage of subjects with at least a 2-fold increase as compared to the Cut-off, for subjects with pre-vaccination T-cell frequencies\<Cut-off, OR, at least a 2-fold increase as compared to pre-vaccination T-cell frequencies for subjects with pre-vaccination T-cell frequencies ≥Cut-off.
Time frame: 30 days after the last vaccination
Number of Participants With solicited local symptoms
Assessed solicited local symptoms were pain, Induration, swelling, redness, pruritus, rash, and cellulitis.
Time frame: Within 7 days after each vaccination
Number of Participants With solicited general symptoms.
Assessed solicited general symptoms were fever \[defined as axillary equal to or above 37.3 degrees Celsius (°C)\], diarrhoea, anorexia, vomiting, nausea, abdominal pain, myalgia, arthralgia, headache, syncope, new convulsions, cough, pruritus (non-vaccination site), skin and mucous membrane abnormalities, acute allergic reactions, fatigue, pain (non-vaccination site), chills.
Time frame: Within 7 days after each dose
Number of Participants With unsolicited adverse events
An unsolicited AE covers 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.
Time frame: During 30 days after each vaccination
Number of Participants With Serious Adverse Events
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From the day of first vaccination up to 12 months after last vaccination
Number of Participants With potential Immune Mediated Disorders
pIMDs are a subset of Adverse Events of Specific Interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Time frame: From the day of first vaccination up to 12 months after last vaccination