A Phase II, Single Center, Randomized, Blind, Controlled Clinical Trial to Evaluate the Immunogenicity and Safety of Recombinant Herpes Zoster Vaccine (CHO Cells) in Healthy Subjects Aged 30 Years and Above
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 924
- 试验地点
- 1
- 主要终点
- The incidence and severity of adverse events
研究概览
简要总结
The purposes of the study are to evaluate the immunogenicity and safety of different dose levels of recombinant herpes zoster vaccine (CHO Cells) with 2 doses at 2-month intervals in healthy subjects aged 30 years and older.
详细描述
The clinical trial will be a single-center, randomized, blind, controlled study in which two dose levels of vaccine will be tested in healthy adults aged 30 to 49 years and 50 years and older. A total of 924 participants will be enrolled, including 396 participants aged 30 to 49 years and 528 participants aged 50 years and older. Participants aged 30 to 49 years will be randomized into three subgroups (low dose vaccine group, high dose vaccine group and placebo group) in a 1:1:1 ratio. Participants aged 50 years and older will be randomized into four subgroups (low dose vaccine group, high dose vaccine group, Shingrix® group and placebo group) in a 1:1:1:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Permanent residents aged 30 years and above;
- •Subjects voluntarily agree to participate in the study and signed an informed consent;
- •Be able to participate in all scheduled visits and comply with the protocol requirements.
排除标准
- •Axillary temperature>37.0℃;
- •History of herpes zoster within 5 years before vaccination;
- •Prior vaccination with chickenpox vaccine or herpes zoster vaccine;
- •Female participant who is pregnant ( urine pregnancy test was positive) or breastfeeding, or has pregnancy plans within 1 year after the last vaccination;
- •Receipt of live vaccine within 28 days, or any other vaccine within 14 days prior to vaccination;
- •Receipt of immunoglobulin or intravenous immunoglobulin within 3 months before vaccination;
- •Acute diseases or acute exacerbation of chronic disease within 3 days before vaccination;
- •A known allergy to any components of the study vaccine (especially allergic to aminoglycoside antibiotics), or history of severe allergy to any previous vaccination;
- •History of convulsions, epilepsy, encephalopathy (such as congenital brain dysplasia, brain trauma, brain tumor, cerebral hemorrhage, cerebral infarction, brain infection disease, nerve tissue damage caused by chemical drug poisoning, etc.) or mental illness and family history;
- •Asplenia or functional asplenia, or splenectomy caused by any condition;
- •Primary or secondary impairment of immune function or diagnosed congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease or other autoimmune diseases;
- •Receipt of immunosuppressive therapy within 3 months before vaccination (such as long-term use of systemic glucocorticoid ≥14 days, dose ≥2mg/kg/day or ≥20mg/day prednisone or equivalent dose), but inhaled, intra-articular and topical steroids are acceptable;
- •Severe cardiovascular disease(eg. Pulmonary heart disease, Pulmonary Edema); Severe liver or kidney disease; or diabetes with complication;
- •History of thrombocytopenia or other coagulation disorders, which may cause intramuscular injection contraindications;
- •Abnormal blood pressure during physical examination before vaccination (systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg);
- •Current or history of alcohol and/or drug abuse;
- •Any condition that, in the opinion the investigator, may affect the safety of the subject or the evaluation of the study results.
研究组 & 干预措施
Shingrix® group in adults aged 50 years and older
Participants aged 50 years and older will be vaccinated with 2 doses of Shingrix® on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Positive control (Biological)
Low dose vaccine group in adults aged 30 to 49 years
Participants aged 30 to 49 years will be vaccinated with 2 doses of low dose recombinant herpes zoster vaccine (CHO cells) on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Low dose Recombinant Herpes Zoster Vaccine (CHO cells) (Biological)
High dose vaccine group in adults aged 30 to 49 years
Participants aged 30 to 49 years will be vaccinated with 2 doses of high dose recombinant herpes zoster vaccine (CHO cells) on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: High dose Recombinant Herpes Zoster Vaccine (CHO cells) (Biological)
Placebo group in adults aged 30 to 49 years
Participants aged 30 to 49 years will be vaccinated with 2 doses of placebo on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Placebo (Biological)
Low dose vaccine group in adults aged 50 years and older
Participants aged 50 years and older will be vaccinated with 2 doses of low dose recombinant herpes zoster vaccine (CHO cells) on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Low dose Recombinant Herpes Zoster Vaccine (CHO cells) (Biological)
High dose vaccine group in adults aged 50 years and older
Participants aged 50 years and older will be vaccinated with 2 doses of high dose recombinant herpes zoster vaccine (CHO cells) on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: High dose Recombinant Herpes Zoster Vaccine (CHO cells) (Biological)
Placebo group in adults aged 50 years and older
Participants aged 50 years and older will be vaccinated with 2 doses of placebo on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Placebo (Biological)
结局指标
主要结局
The incidence and severity of adverse events
时间窗: Within 30 days after each vaccination
Incidence and severity of adverse events within 30 days after each vaccination. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.
Seroresponse rate of anti-gE antibody
时间窗: Month 1 after the last vaccination
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.
Geometric Mean Fold Rise (GMFR) of anti-gE antibody concentration
时间窗: Month 1 after the last vaccination
The antibody concentration at month 1 after the last vaccination compared with that at baseline (Day 0).
Vaccine Response Rate (VRR)
时间窗: Month 1 after the last vaccination
VRR is defined as the percentage of participants with T-cell frequencies are ≥Cut-off value, for participants with T-cell frequencies\<Cut-off at baseline, OR, at least a 2-fold increase as compared to baseline for participants with T-cell frequencies ≥Cut-off value at baseline.
Geometric mean concentration (GMC) of anti-gE antibody
时间窗: Month 1 after the last vaccination
Measured by ELISA.
Four-fold increase rate of anti-gE antibody concentration
时间窗: Month 1 after the last vaccination
The antibody concentration at month 1 after the last vaccination compared with that at baseline (Day 0).
Seropositivity rate of anti-gE antibody
时间窗: Month 1 after the last vaccination
The seropositivity rate is defined as the percentage of seropositive subjects. A seronegative subject is a subject whose antibody concentration is below the cut-off value. A seropositive subject is a subject whose antibody concentration is greater than or equal to the cut-off value.
Cell-Mediated Immunity (CMI) response
时间窗: Month 1 after the last vaccination
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.
次要结局
- Seropositivity rate of anti-VZV antibody(At 6, 12 and 24 months after the last vaccination)
- Seropositivity rate of anti-gE antibody(At 6, 12 and 24 months after the last vaccination)
- Cell-Mediated Immunity (CMI) response(At 6, 12 and 24 months after the last vaccination)
- Vaccine Response Rate (VRR)(At 6, 12 and 24 months after the last vaccination)
- The incidence of Serious Adverse Events(From the first vaccination to 12 months after the last vaccination)
- Four-fold increase rate of anti-VZV antibody(Month 1 after the last vaccination)
- Geometric mean concentration (GMC) of anti-VZV antibody(At 6, 12 and 24 months after the last vaccination)
- Geometric mean concentration (GMC) of anti-gE antibody(At 6, 12 and 24 months after the last vaccination)
- Potential Immune-Mediated Diseases(From the first vaccination to 12 months after the last vaccination)
- Geometric Mean Fold Rise (GMFR) of anti-VZV antibody(Month 1 after the last vaccination)
- Seroresponse rate of anti-VZV antibody(Month 1 after the last vaccination)