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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Herpes Zoster (HZ)
• Intervention / Treatment: Biological: Positive control; Biological: Low dose antigen and low dose adjuvant of LYB004; Biological: Low dose antigen and high dose adjuvant of LYB004; Biological: Placebo; Biological: High dose antigen and low dose adjuvant of LYB004; Biological: High dose antigen and high dose adjuvant of LYB004

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.

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Renfeng Fan; Phone Number: 8613560231815; Email: gdsjkzx_sws_sps@gd.gov.cn

Study Locations

• China
  • Meizhou, China
    • Recruiting
    • Guangdong Provincial Center for Disease Control and Prevention
    • Contact: Weihua Huang; Phone Number: 8613690896555; Email: 2051274292@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects aged 40 years and older will be vaccinated with 2 doses of placebo on a 0, 2 month schedule, administered intramuscularly (IM).	Biological: Placebo; 0.5 mL per dose, without antigen and adjuvant.
Experimental: Low dose antigen and low dose adjuvant of LYB004; Subjects aged 40 years and older will be vaccinated with 2 doses of LYB004 (low dose antigen and low dose adjuvant) on a 0, 2 month schedule, administered intramuscularly (IM).	Biological: 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.
Experimental: Low dose antigen and high dose adjuvant of LYB004; Subjects aged 40 years and older will be vaccinated with 2 doses of LYB004 (low dose antigen and high dose adjuvant ) on a 0, 2 month schedule, administered intramuscularly (IM).	Biological: 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.
Active Comparator: Positive control; Subjects aged 50 years and older will be vaccinated with 2 doses of Shingrix® on a 0, 2 month schedule, administered intramuscularly (IM).	Biological: Positive control; 0.5 mL per dose, containing a total of 50 µg recombinant varicella zoster virus glycoprotein E, adjuvanted with AS01B.; Other Names: Shingrix®
Experimental: High dose antigen and low dose adjuvant of LYB004; Subjects aged 40 years and older will be vaccinated with 2 doses of LYB004 (high dose antigen and low dose adjuvant) on a 0, 2 month schedule, administered intramuscularly (IM).	Biological: 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.
Experimental: High dose antigen and high dose adjuvant of LYB004; Subjects aged 40 years and older will be vaccinated with 2 doses of LYB004 (high dose antigen and high dose adjuvant) on a 0, 2 month schedule, administered intramuscularly (IM).	Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of immediate adverse events	The incidence and severity of any adverse events (AEs) within 30 minutes after each vaccination	Within 30 minutes after each vaccination
Incidence of solicited AE	Occurrence and severity of solicited local injection site reactions for 14 days (Day 0-Day 14) following each vaccination. (i.e., pain, redness, swelling). Occurrence and severity of solicited systemic reactions for 14 days (Day 0-Day 14) following each vaccination. (i.e., myalgia, fatigue, headache, chills, fever).	Within 0-14 days after each vaccination
Incidence of unsolicited AEs	The incidence and severity of any unsolicited AEs, including all AEs, except solicited AEs reported Days 0~30 after the study intervention. vaccination	Within 30 days after each vaccination
Incidence of clinically significant abnormalities in clinical laboratory tests	The incidence of clinically significant abnormalities in clinical laboratory tests (hematology, blood chemistry, coagulation function, and urinalysis) on Day 3 after each vaccination	3 days after each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of serious adverse events (SAEs) and adverse events of special interests (AESIs)	The incidence of any serious adverse events (SAEs) and adverse events of special interest (AESIs) from the first vaccination up to 12 months after the second vaccination	From the first vaccination up to 12 months after the second vaccination
The seroconversion rate of anti-Varicella Zoster Virus (VZV) antibody	Seroconversion refers to at least a 4-fold increase in the anti-Varicella Zoster Virus (VZV) antibody titer at the endpoint as compared to the prevaccination titer if prevaccination titer is above the lower limit of quantification (LLOQ) or a 4-fold increase at the endpoint as compared to LLOQ value if prevaccination concentration is lower than LLOQ.	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	Seroconversion refers to at least a 4-fold increase in the anti-glycoprotein E (gE) antibody concentration at the endpoint as compared to the prevaccination concentration if prevaccination concentration is above the lower limit of quantification (LLOQ) or a 4-fold increase at the endpoint as compared to LLOQ value if prevaccination concentration is lower than LLOQ.	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	Measured by fluorescent antibody to the membrane antigen (FAMA).	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	Measured by Enzyme-Linked Immunosorbent Assay (ELISA).	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	The frequencies of CD4+ T cells secreting at least two of gE specific activation markers (IFN-γ, IL-2, TNF-α, CD40L) per 106 CD4+ T cells, and the cell mediated immunity (CMI) response rates at 30 days after first vaccination, 30 days and 6 months after second vaccination.	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	The 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 30 days after first vaccination, 30 days and 6 months after second vaccination.	30 days after first vaccination, 30 days and 6 months after second vaccination
The geometric mean fold rise (GMFR) of anti-VZV antibody	Change from prevaccination in geometric mean fold rise of anti-VZV antibody titer.	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	Change from prevaccination in geometric mean fold rise of anti-gE antibody concentration.	30 days and 60 days after first vaccination, 14 days, 30 days, 6 months and 12 months after second vaccination

Collaborators and Investigators

• Sponsor: Guangzhou Patronus Biotech Co., Ltd.
• Investigators: Principal Investigator: Renfeng Fan, Guangdong Center for Disease Prevention and Control

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: vaccine; herpes zoster; shingles; varicella zoster virus; Virus-Like Particles
• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Herpes Zoster
• Other Study ID Numbers: LYB004/CT-CHN-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No