A Phase I, Single Center, Randomized, Blinded, Controlled Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Immunogenicity of Recombinant Herpes Zoster Vaccine (CHO Cells) in Healthy Subjects Aged 18 Years and Above
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 132
- 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 safety and tolerability of different dose levels of recombinant herpes zoster vaccine (CHO Cells) with 2 doses at 2-month intervals in healthy subjects aged 18 years and older, and to preliminarily explore immunogenicity.
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 18 to 49 years and 50 years and older, with progression from low dose level to high dose level and younger age group to the older age group based on assessment of safety and tolerability. The younger cohort (aged 18 to 49 years) will consist of 60 subjects, 30 per dose level, and these 30 subjects will be randomized into three subgroups, including vaccine group, adjuvant group and normal saline group, with randomization ratio of 2:2:1. The older cohort (aged 50 years and older) will consist of 72 subjects, 36 per dose level, and these 36 subjects will be randomized into four subgroups, including vaccine group, adjuvant group, Shingrix® group and normal saline group, with randomization ratio of 2:2:1:1.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Permanent residents aged 18 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);
- •Abnormal and clinically significant laboratory test results as determined by the investigator before vaccination;
- •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
Low dose vaccine group in adults aged 18 to 49 years
Subjects aged 18 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)
Low dose adjuvant group in adults aged 18 to 49 years
Subjects aged 18 to 49 years will be vaccinated with 2 doses of low dose adjuvant on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Low dose adjuvant (Biological)
Low dose vaccine group in adults aged 50 years and older
Subjects 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 18 to 49 years
Subjects aged 18 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)
High dose adjuvant group in adults aged 18 to 49 years
Subjects aged 18 to 49 years will be vaccinated with 2 doses of high dose adjuvant on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: High dose adjuvant (Biological)
Placebo group in adults aged 18 to 49 years
Subjects aged 18 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 adjuvant group in adults aged 50 years and older
Subjects aged 50 years and older will be vaccinated with 2 doses of low dose adjuvant on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: Low dose adjuvant (Biological)
High dose vaccine group in adults aged 50 years and older
Subjects 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)
High dose adjuvant group in adults aged 50 years and older
Subjects aged 50 years and older will be vaccinated with 2 doses of high dose adjuvant on a 0, 2 month schedule, administered intramuscularly (IM).
干预措施: High dose adjuvant (Biological)
Shingrix® group in adults aged 50 years and older
Subjects 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)
Placebo group in adults aged 50 years and older
Subjects 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.
Incidence of abnormal and clinically significant laboratory test results
时间窗: Day 4 after each vaccination .
Laboratory test includes hematology, blood biochemistry and urine analysis.
次要结局
- Incidence of Serious Adverse Event(From the first vaccination to 12 months after full vaccination (From Day 0 to Day 420).)
- Geometric mean increase(GMI) of anti-gE antibody and anti-VZV antibody concentration(Month 1 after each vaccination (Day 30, Day 90))
- Four-fold increase rate of the anti-gE antibody and anti-VZV antibody concentration(Month 1 after each vaccination (Day 30, Day 90).)
- Frequency of gE-specific CD4+ T-cells expressing at least 1 Immunological activation marker(Month 6, 12 after the second vaccination (Day 240, Day 420).)
- Potential Immune Mediated Disorder(From the first vaccination to 12 months after full vaccination (From Day 0 to Day 420).)
- Geometric mean concentration (GMC) of anti-gE antibody and anti-VZV antibody(Month 6 and 12 after the second vaccination (Day 240, Day 420).)
- Seroconversion rate of anti-gE antibody and anti-VZV antibody(Month 1 after each vaccination (Day 30, Day 90).)
- Positive rate of anti-gE antibody and anti-VZV antibody(Month 6 and 12 after the second vaccination (Day 240, Day 420).)
- Cellular immune response(Month 6, 12 after the second vaccination (Day 240, Day 420))