Clinical trial NCT06874842: Safety and Immunogenicity of the Recombinant Zoster Vaccine, LYB004 in Adults Aged 40 Years and Older
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Herpes Zoster (HZ)
Keywords: herpes zoster
shingles
varicella zoster virus
Virus-Like Particles
vaccine
Lead sponsor: Guangzhou Patronus Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-03-13
Enrollment: 92
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A total of 92 healthy subjects will be enrolled and stratified by age (40-49 years，50-59 years and ≥60 years in a 5:6:8 ratio). The younger cohort (aged 40 to 49 years) will consist of 20 subjects, and these 20 subjects will be enrolled into five subgroups, including four vaccine groups, and placebo group, with the ratio of 1:1:1:1:1. The middle age cohort (aged 50 to 59 years) will consist of 24 subjects, and these 24 subjects will be enrolled into six subgroups, including four vaccine groups, placebo group and positive control group/Shingrix® group, with the ratio of 1:1:1:1:1:1. The older cohort (aged ≥60 years) will consist of 48 subjects, and these 48 subjects will be enrolled into six subgroups, including four vaccine groups, placebo group and positive control group/Shingrix® group, with the ratio of 1:1:1:1:1:1. The investigational vaccine group and the control group (placebo and positive control) are enrolled parallelly.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Residents aged 40 years and older (at the time of screening), regardless of gender;
2. Participants can provide valid identification, voluntarily agree to participate in the study, and sign the Informed Consent Form;
3. Participants are able to attend all planned follow-up visits and comply with the protocol requirements;
4. 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.

Exclusion Criteria:

1. Axillary temperature ≥ 37.3°C;
2. History of herpes zoster before vaccination with the investigational vaccine;
3. Previous vaccination against HZ or varicella;
4. Has had close contact with patients with varicella/herpes zoster within 6 months before vaccination with the investigational vaccine;
5. Has received any vaccine within 14 days before vaccination, or have received a live vaccine within 28 days;
6. Have been injected with gamma globulin or intravenous immunoglobulin within 3 months before vaccination;
7. 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);
8. Abnormal laboratory test indicators specified in the protocol before vaccination and determined by the clinical investigator to be of clinical significance;
9. History of long-term alcohol abuse and/or drug abuse;
10. 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;
11. 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;
12. Other conditions that may impact the subject's safety or influence the assessment of vaccine response, as determined by the investigator.

Primary outcomes:
measure: Occurrence of immediate adverse events
timeFrame: Within 30 minutes after each vaccination
measure: Incidence of solicited AE
timeFrame: Within 0-14 days after each vaccination
measure: Incidence of unsolicited AEs
timeFrame: Within 30 days after each vaccination
measure: Incidence of clinically significant abnormalities in clinical laboratory tests
timeFrame: 3 days after each vaccination
Secondary outcomes:
measure: Occurrence of serious adverse events (SAEs) and adverse events of special interests (AESIs)
timeFrame: From the first vaccination up to 12 months after the second vaccination
measure: The seroconversion rate of anti-Varicella Zoster Virus (VZV) antibody
timeFrame: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination
measure: The seroconversion rate of anti-glycoprotein E (gE) antibody
timeFrame: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination
measure: The geometric mean titer (GMT) of anti-VZV antibody
timeFrame: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination
measure: The geometric mean concentration (GMC) of anti-glycoprotein E (gE) antibody
timeFrame: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination
measure: The geometric mean fold rise (GMFR) of anti-VZV antibody
timeFrame: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination
measure: The GMFR of anti-gE antibody
timeFrame: 30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination
measure: 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
timeFrame: 30 days after first vaccination, 30 days and 6 months after second vaccination
measure: 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
timeFrame: 30 days after first vaccination, 30 days and 6 months after second vaccination
Other outcomes:
Locations:
city: Meizhou
country: China
facility: Guangdong Provincial Center for Disease Control and Prevention
Study officials:
affiliation: Guangdong Center for Disease Prevention and Control
name: Renfeng Fan
role: PRINCIPAL_INVESTIGATOR
References: