Phase I Clinical Trial of a Candidate Herpes Zoster Vaccine

Study Overview
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Brief Summary
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This is a phase I, randomized, observer-blinded study to evaluate the safety, tolerability, and immunogenicity of BV211(a herpes zoster vaccine) in Adult Volunteers.

Official Title
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A Phase I, Randomized, Observer-blinded Study to Evaluate the Safety, Tolerability, and Immunogenicity of BV211 in Adult Volunteers

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Recombinant Zoster Vaccine
* Biological: Placebo
* Biological: Zoster Vaccine Recombinant, Adjuvanted


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy resident aged 30-70 years with body weight ≥ 50 kg for males and ≥ 45 kg for females, BMI within the range of 19.0-32.0 (including the boundary value), who can provide legal identification. Willing to participate in the study and sign ICF. Women of childbearing age shall take effective contraception measures 30 days before vaccination up to 6 months post full vaccination and not in lactation period. The pregnancy test on the day of vaccination shall be negative. Will attend all scheduled follow-up visits and follow the requirements of the clinical study. Exclusion Criteria: Smoking, and/or excessive alcohol use. Failed the screening test of illicit drugs, including THC. Axillary temperature above 37.3℃. History of herpes zoster. Received any herpes zoster vaccine. Received any vaccine within 14 days or live vaccine within 28 days before vaccination. Received gamma immunoglobulin or intravenous immunoglobulin within 3 months before vaccination. Have acute illness or are in the acute exacerbation phase of a chronic disease within 3 days before vaccination. Allergic history to any vaccine-related component; history of severe allergies to any vaccine. History of convulsions, epilepsy or encephalopathy (such as congenital brain hypoplasia, brain trauma, brain tumor, cerebral hemorrhage, cerebral infarction, brain infection, damage to nerve tissue in brain caused by chemical drug poisoning, etc.) and psychiatric history or family history of mental illness. Asplenia or functional asplenia, and asplenia or splenectomy caused by any reason. Primary or secondary immunocompromised or diagnosed with congenital or acquired immunodeficiency, infection of HIV, lymphoma, leukemia, SLE, JRA, inflammatory bowel disease or other autoimmune diseases. Received immunosuppressive therapy (such as long-term application of systemic glucocorticoids ≥ 14 days, dose ≥ 2 mg/kg/day or prednisone ≥ 20mg/day or equivalent to that dose of prednisone, excluding inhaled, intra-articular and topical steroid) within 3 months before vaccination. Serious cardiovascular diseases (pulmonary heart disease, pulmonary edema), liver and renal diseases and diabetes with complications. History of thrombocytopenia or other coagulation disorders, which may cause contraindications to intramuscular injection. Abnormal blood pressure (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) before vaccination; abnormal ECG Laboratory indicators out of the specified ranges (i.e., out of 1.5x of ULN or LLN), or with clinical significance as judged by the physician. Current/long-term history of alcohol abuse and/or history of drug abuse. Any other factors judged by investigator that may affect the safety of the subject or evaluation of the study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY<br>Young adult subjects received low dose of BV211 | Biological: Recombinant Zoster Vaccine<br>* 0.5mL, Intramuscular<br>* Other names: BV211;|
| Experimental: HY<br>Young adult subjects received high dose of BV211 | Biological: Recombinant Zoster Vaccine<br>* 0.5mL, Intramuscular<br>* Other names: BV211;|
| Placebo Comparator: Placebo<br>Young adult subjects received placebo | Biological: Placebo<br>* 0.5mL, Intramuscular<br>|
| Experimental: LO<br>Old adult subjects received low dose of BV211 | Biological: Recombinant Zoster Vaccine<br>* 0.5mL, Intramuscular<br>* Other names: BV211;|
| Experimental: HO<br>Old adult subjects received high dose of BV211 | Biological: Recombinant Zoster Vaccine<br>* 0.5mL, Intramuscular<br>* Other names: BV211;|
| Active Comparator: Control Vaccine<br>Old adult subjects received control vaccine | Biological: Zoster Vaccine Recombinant, Adjuvanted<br>* 0.5mL, Intramuscular<br>* Other names: Shingrix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety in terms of adverse reactions/events | Incidence rates of adverse reactions/events (ADRs/AEs) | 30 mins, 0-7 days, 8-30 days and 0-30 days | 
| Safety in terms of laboratory-based AEs | Incidence rates of abnormal laboratory indicators | 3 days after each vaccination | 
| Safety in terms of SAEs | Incidence rates of SAEs | Within 6 months after full vaccination | 
| Safety in terms of Adverse Events of Special Interest | Incidence rates of AESI | Within 6 months after full vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogencity in terms of GMT by ELISA or FAMA | GMC of anti-gE antibody and GMT of anti-VZV antibody | Days 1, 30, 60, 90 and 240 | 
| Immunogencity in terms of Seroconversion Rates | Seroconversion rates of anti-gE and anti-VZV antibody responses | Days 30, 60, 90 and 240 | 
| Immunogencity in terms of Geometric Mean Fold Increase | GMFI of anti-gE and anti-VZV antibody responses | Days 30, 60, 90 and 240 | 
| Immunogencity in terms of Cellular immunity | Frequency of CD4+ and CD8+T cells that express at least one cytokine | Days 1, 90 and 240 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herpes Zoster Vaccine, BV211