Safety and Immunogenicity of the Recombinant Zoster Vaccine, LYB004 in Adults Aged 40 Years and Older

Официальное название

A Phase I, Randomized, Observer-blinded, Parallel-Controlled, Dose Escalation Clinical Trial to Assess the Safety and Immunogenicity of the Recombinant Zoster Vaccine, LYB004 in Adults Aged 40 Years and Older

Обзор

This phase 1 study in China will evaluate the safety and immunogenicity of the Recombinant Zoster Vaccine, LYB004 in adults aged 40 years and older.

Подробное описание

A randomized, observer-blinded, positive-controlled, dose escalation trial will be conducted to observe the safety and immunogenicity of LYB004 in adults aged 40 years and older. A total of 92 healthy subjects will be enrolled and stratified by age (40-49，50-59 years and ≥60 years in a 5:6:8 ratio). Four formulations of LYB004 will be provided, two dose levels of antigen and two dose levels of adjuvant.

A sentinel and escalating dosing approach will be used for close monitoring of safety to minimize risk to participants. Participants will be enrolled in one of six cohorts, including Cohort 1 (40-49 years, low dose, n=10), Cohort 2 (50-59 years, low dose, n=12), Cohort 3 (≥60 years, low dose, n=24), Cohort 4 (40-49 years, high dose, n=10), Cohort 5 (50-59 years, high dose, n=12), and Cohort 6 (≥60 years, high dose, n=24). In Cohort 1 and Cohort 4, three sentinels each were set up, and they were randomly vaccinated with the investigational vaccine (low dose adjuvant), the investigational vaccine (high dose adjuvant), or a placebo in a 1:1:1 ratio. The remaining participants were randomly vaccinated in a 3:3:1 ratio with the low dose investigational vaccine (low dose adjuvant), the low dose investigational vaccine (high dose adjuvant), or a placebo. In Cohort 2 and Cohort 5, four sentinels each were set up, and they were randomly vaccinated with the investigational vaccine (low dose adjuvant), the investigational vaccine (high dose adjuvant), a positive control/Shingrix®, or a placebo in a 1:1:1:1 ratio. The remaining participants were randomly vaccinated in a 3:3:1:1 ratio with the same options. In Cohort 3 and Cohort 6, four sentinels each were also set up, and they were randomly vaccinated in a 1:1:1:1 ratio with the investigational vaccine (low dose adjuvant), the investigational vaccine (high dose adjuvant), a positive control/Shingrix®, or a placebo. The remaining participants were randomly vaccinated in a 7:7:3:3 ratio with the same options. The two-dose immunization schedule will be adopted, that is, LYB004 or Shingrix® or placebo will be intramuscularly injected on Day 0 and Day 60, respectively.

Вмешательства

• Биопрепарат Low dose antigen and low dose adjuvant of LYB004
  0.5 mL per dose, containing a total of 25 μg VZV-gEM adjuvanted with A01C.
• Биопрепарат Low dose antigen and high dose adjuvant of LYB004
  0.5 mL per dose, containing a total of 25 μg VZV-gEM adjuvanted with A01B.
• Биопрепарат High dose antigen and low dose adjuvant of LYB004
  0.5 mL per dose, containing a total of 50 μg VZV-gEM adjuvanted with A01C.
• Биопрепарат High dose antigen and high dose adjuvant of LYB004
  0.5 mL per dose, containing a total of 50 μg VZV-gEM adjuvanted with A01B.
• Биопрепарат Placebo
  0.5 mL per dose, without antigen and adjuvant.
• Биопрепарат Positive control
  0.5 mL per dose, containing a total of 50 µg recombinant varicella zoster virus glycoprotein E, adjuvanted with AS01B.

Первичные конечные точки

• Occurrence of immediate adverse events [Срок оценки: Within 30 minutes after each vaccination]
• Incidence of solicited AE [Срок оценки: Within 0-14 days after each vaccination]
• Incidence of unsolicited AEs [Срок оценки: Within 30 days after each vaccination]
• Incidence of clinically significant abnormalities in clinical laboratory tests [Срок оценки: 3 days after each vaccination]

Вторичные конечные точки (9)

• Occurrence of serious adverse events (SAEs) and adverse events of special interests (AESIs) [Срок оценки: From the first vaccination up to 12 months after the second vaccination]
• The seroconversion rate of anti-Varicella Zoster Virus (VZV) antibody [Срок оценки: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination]
• The seroconversion rate of anti-glycoprotein E (gE) antibody [Срок оценки: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination]
• The geometric mean titer (GMT) of anti-VZV antibody [Срок оценки: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination]
• The geometric mean concentration (GMC) of anti-glycoprotein E (gE) antibody [Срок оценки: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination]
• The geometric mean fold rise (GMFR) of anti-VZV antibody [Срок оценки: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination]
• The GMFR of anti-gE antibody [Срок оценки: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination]
• Frequencies of CD4+ T cells secreting at least two of gE specific activation markers (IFN-γ, IL-2, TNF-α, CD40L) per 10^6 CD4+ T cells, and the cell mediated immunity (CMI) response rates at timepoints during the study [Срок оценки: 30 days after first vaccination, 30 days and 6 months after second vaccination]
• Frequencies of CD8+ T cells secreting at least two of gE specific activation markers (IFN-γ, IL-2, TNF-α, CD40L) per 10^6 CD8+ T cells, and the cell mediated immunity (CMI) response rates at timepoints during the study [Срок оценки: 30 days after first vaccination, 30 days and 6 months after second vaccination]

Критерии участия

Критерии включения

• Residents aged 40 years and older (at the time of screening), regardless of gender;
• Participants can provide valid identification, voluntarily agree to participate in the study, and sign the Informed Consent Form;
• Participants are able to attend all planned follow-up visits and comply with the protocol requirements;
• Females of childbearing potential should use effective contraceptive measures one month before enrollment; females of childbearing potential (excluding those who have undergone tubal ligation, bilateral oophorectomy, or hysterectomy) and male participants should practice effective contraception and avoid pregnancy plans, as well as sperm or egg donation plans from the time of enrollment until 6 months after the full course of vaccination. Effective contraceptive methods include oral contraceptives (excluding emergency contraceptives), injectable or implantable contraceptives, sustained-release local contraceptives, contraceptive patches, intrauterine devices, sterilization, abstinence, condoms, diaphragms, cervical caps, etc.

Критерии исключения

• Axillary temperature ≥ 37.3°C;
• History of herpes zoster before vaccination with the investigational vaccine;
• Previous vaccination against HZ or varicella;
• Has had close contact with patients with varicella/herpes zoster within 6 months before vaccination with the investigational vaccine;
• Has received any vaccine within 14 days before vaccination, or have received a live vaccine within 28 days;
• Have been injected with gamma globulin or intravenous immunoglobulin within 3 months before vaccination;
• Individual with the following diseases: ① Have acute diseases or are in the acute exacerbation period of chronic diseases, or take antipyretic, analgesic, and anti-allergic drugs within 3 days before vaccination; ② Allergies to any component of the study vaccine, or have a history of severe allergic reactions to any vaccination; ③ History of convulsions, epilepsy, encephalopathy (such as congenital brain dysplasia, brain trauma, brain tumors, cerebral hemorrhage, cerebral infarction, brain infection, chemical poisoning, etc. causing brain nerve tissue damage, etc.) and mental illness, or a family history of mental illness; ④ Asplenia, or functional asplenia; ⑤Primary or secondary immunodeficiency, or diagnosed with congenital or acquired immunodeficiency, human immunodeficiency virus infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune diseases; ⑥ Chronic administration (≥14 consecutive days) of glucocorticoid (reference value for dose: ≥ 2mg/kg/day or ≥ 20mg/day prednisone or equivalent) or other immunosuppressive agents within the past 3 months, with the exception of inhaled or topical steroids, or short-term use (<14 consecutive days) of oral corticosteroids; ⑦ Severe cardiovascular diseases (pulmonary heart disease, pulmonary edema, etc.), severe liver and kidney diseases, complicated diabetes; ⑧ History of thrombocytopenia or other coagulation disorders that may contraindicate intramuscular injection;⑨Severe hypertension that cannot be controlled by medication (on-site measurement: systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg);
• Abnormal laboratory test indicators specified in the protocol before vaccination and determined by the clinical investigator to be of clinical significance;
• History of long-term alcohol abuse and/or drug abuse;
• Individual who is currently participating in other research or unregistered product (drugs, vaccines, or devices, etc.) clinical studies, or plan to participate in other clinical studies before the end of this clinical study;
• Exclusion criteria for specific populations: lactating or pregnant women during the clinical research period, or women of childbearing age with a positive pregnancy test before vaccination;
• Other conditions that may impact the subject's safety or influence the assessment of vaccine response, as determined by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Guangdong Provincial Center for Disease Control and Prevention — Meizhou

Идентификаторы

NCT: NCT06874842 · LYB004/CT-CHN-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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