A Safety and Immunogenicity Trial of the Recombinant Zoster Vaccine （CHO Cell）, LYB004 in Adults Aged 50 to 70 Years

A Phase I, Randomized, Observer-blinded, Positive-Controlled, Dose Escalation Clinical Trial to Assess the Safety and Immunogenicity of the Recombinant Zoster Vaccine （CHO Cell）, LYB004 in Adults Aged 50 to 70 Years

This phase 1 study in Australia will evaluate the safety and immunogenicity of the Recombinant Zoster Vaccine (CHO Cell), LYB004 in Adults Aged 50 to 70 Years.

Study Overview

• Status: Not yet recruiting
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: LYB004 25µg; Biological: LYB004 50µg; Biological: SHINGRIX

Detailed Description

A randomized, observer-blinded, positive-controlled, dose escalation trial will be conducted to observe the safety and immunogenicity of LYB004 in adults 50 to 70 years of age. A total of 48 healthy subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:1) to receive LYB004 or SHINGRIX. Two dose levels of LYB004 will be provided, low dose 25 μg and high dose 50 μg. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60, respectively.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Katherine Gunn; Phone Number: 0737072781; Email: k.gunn@nucleusnetwork.com.au
• Study Contact Backup: Name: Kristof Boot; Phone Number: 0737072780; Email: k.boot@nucleusnetwork.com.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd
      • Contact: Katherine Gunn; Phone Number: (07) 3707 2781; Email: k.gunn@nucleusnetwork.com.au
      • Contact: Kristof Boot; Phone Number: (07) 3707 2780; Email: k.boot@nucleusnetwork.com.au
      • Principal Investigator: Christina Chang, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. A male or female aged 50 to 70 years inclusive at screening.
2. Written informed consent obtained from the subject before any assessment is performed.
3. Subjects who the investigator believes that they can and will comply with the requirements of the protocol. (e.g., complete the diary cards, and complete follow-up visits).
4. Subjects must have a Body Mass Index (BMI) between ≥18.0 and ≤35.0 kg/m^2 at screening.

5. Female subjects who are not pregnant or lactating. Female subjects with childbearing potential and their partners should use highly effective, medically accepted double-barrier contraception and will not have pregnancy and fertility plan until study completion.

   • Female subjects of childbearing potential are defined as sexually mature women: 1) have not undergone hysterectomy, bilateral salpingectomy, and bilateral oophorectomy; 2) have had natural menses at any time in the preceding 12 consecutive months (without an alternative medical cause).
   • Highly effective double-barrier contraception is defined as use of a condom AND one of the following: Birth control pills (The Pill), Depot or injectable birth control, Intrauterine device (IUD), Birth Control Patch (e.g., Ortho Evra), NuvaRing®, Implantable contraception (e.g., Implanon).
6. Males participating in this study must agree to use highly effective, medically accepted double-barrier contraception (as described above) and refrain from donating sperm until study completion.

Exclusion Criteria:

1. Tympanic temperature > 37.5°C at screening.
2. History of HZ.
3. Previous vaccination against HZ or varicella. Planned administration of VZV or HZ vaccination during the study (including an investigational or non-registered vaccine), except for the investigational vaccine.
4. Received a live attenuated vaccine within 28 days before vaccination or received other vaccines within 14 days before vaccination.
5. Received any immunoglobulins or blood/plasma products within 3 months prior to vaccination.
6. Individuals with the following diseases: 1）Any acute disease or acute attack of chronic diseases or using antipyretic, analgesic or anti-allergic drugs (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.) within 3 days prior to enrolment; 2）Allergies to any component of the investigational vaccine; 3）Subject has any clinically significant history of allergic conditions to other vaccines. 4）History of neurological disorders (convulsions, epilepsy, encephalopathy, etc.) or psychiatric disorders (bipolar disorder, schizophrenia, etc.) that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study; 5）Asplenia, or functional asplenia; 6）Congenital or acquired immunodeficiency or autoimmune disease; 7）Chronic administration (≥14 consecutive days) of glucocorticoid (reference value for dose: ≥20 mg/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; 8）Has severe cardiovascular diseases (cardiopulmonary disease, pulmonary edema), severe hepatic or renal diseases, and diabetes complications that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study; 9）History of thrombocytopenia or other coagulation disorders which may be contraindications for an IM; 10）Severe hypertension uncontrolled by medication with systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg; 11）Positive test for Hepatitis C virus (HCV), Hepatitis B surface antigen (HbsAg), Human immunodeficiency virus (HIV) at screening; 12）Any skin condition and/or tattoo that may interfere with the evaluation of safety at the injection site.
7. Clinically significant laboratory abnormalities determined by the investigator prior to vaccination.
8. A positive urine drug test or alcohol breath test or a history of drug or alcohol abuse in the past 1 years.
9. Recent participation in another clinical trial, with receipt of the investigational drug/vaccine within 30 days prior to screening. Current participation or those planning to participate in another clinical trial during the study.
10. 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: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1 (LYB004 25µg); Subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:2:1) to receive 25 μg LYB004, 50 μg LYB004 or SHINGRIX. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60.	Biological: LYB004 25µg; Subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:2:1) to receive 25 μg LYB004, 50 μg LYB004 or SHINGRIX. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60.
Experimental: Treatment 2 (LYB004 50µg); Subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:2:1) to receive 25 μg LYB004, 50 μg LYB004 or SHINGRIX. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60.	Biological: LYB004 50µg; Subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:2:1) to receive 25 μg LYB004, 50 μg LYB004 or SHINGRIX. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60.
Active Comparator: Treatment 3 (SHINGRIX); Subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:2:1) to receive 25 μg LYB004, 50 μg LYB004 or SHINGRIX. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60.	Biological: SHINGRIX; Subjects will be enrolled and stratified by age (50-59 years and 60-70 years in a 1:1 ratio) and randomized (2:2:1) to receive 25 μg LYB004, 50 μg LYB004 or SHINGRIX. The two-dose immunization schedule will be adopted, that is, LYB004 or SHINGRIX will be intramuscularly injected on Day 0 and Day 60.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the reactogenicity of LYB004 vaccine	The incidence and severity of any adverse events (AEs) within 30 minutes after each vaccination	Within 30 minutes after each vaccination
Evaluate the safety and reactogenicity of LYB004 vaccine	The incidence and severity of any solicited local and systemic AEs and unsolicited AEs within 0-7 days after each vaccination	Within 0-7 days after each vaccination
Evaluate the safety of LYB004 vaccine	The incidence and severity of any AEs within 8-30 days after each vaccination	Within 8-30 days after each vaccination
Evaluate the safety and tolerability in laboratory tests of LYB004 vaccine	The occurrence of clinically significant laboratory abnormalities 3 days, 14 days after each vaccination and 90 days after the first vaccination	3 days, 14 days after each vaccination and 90 days after the first vaccination
Evaluate the SAEs and AESIs of LYB004 vaccine	The incidence of any serious adverse events (SAEs) and adverse events of special interest (AESIs) from the first vaccination up to 6 months after the second vaccination	From the first vaccination up to 6 months after the second vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observe the humoral immunity of LYB004 vaccine	The geometric mean concentration (GMC in mIU/ml), geometric mean fold rise (GMFR), and serum seroconversion rate (%) of gE antibodies at 14 and 30 days after each vaccination; the geometric mean titer (GMT in 1:X), GMFR, and serum seroconversion rate (%) of VZV antibodies at 14 and 30 days after each vaccination	At 14 and 30 days after each vaccination
Observe the cellular immunity of LYB004 vaccine	The frequency and the cell mediated immunity (CMI) response rate (%) of gE-specific CD4^2+ and CD8^2+ T cells (expressing at least 2 different activation markers: IFN-γ, IL-2, TNF-α, and CD40L) per 10^6 CD4 and CD8 T cells at 30 days after the second vaccination	At 30 days after the second vaccination
Observe the persistence of humoral immunity of LYB004 vaccine	The GMC in mIU/ml, GMFR, and serum seroconversion rate (%) of gE antibodies at 6 months after the second vaccination; the GMT in 1:X, GMFR, and serum seroconversion rate (%) of VZV antibodies at 6 months after the second vaccination	At 6 months after full vaccination
Observe the persistence of cellular immunity of LYB004 vaccine	The frequency and the CMI response rate (%) of gE-specific CD4^2+ and CD8^2+T cells per 10^6 CD4 and CD8 T cells at 6 months after the second vaccination	At 6 months after full vaccination

Collaborators and Investigators

• Sponsor: Guangzhou Patronus Biotech Co., Ltd.
• Collaborators: Yantai Patronus Biotech Co., Ltd.
• Investigators: Principal Investigator: Christina Chang, M.D, Nucleus Network Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Shingles; Herpes zoster; Varicella-Zoster Virus; Recombinant Zoster Vaccine; Glycoprotein E
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster
• Other Study ID Numbers: LYB004-CT-AUS-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