A Study to Evaluate Safety and Tolerability of a Recombinant Herpes Zoster Vaccine

Study Overview
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Brief Summary
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This clinical trial is to study the safety and tolerability of a recombinant herpes zoster vaccine (LZ901) and sponsored by Beijing Luzhu Biotechnology Co., Ltd. It is a phase I, randomized, double-blind, placebo-controlled, dose escalation study in healthy people aged 50 to 70 years inclusive. The study is to protect adults against shingles (herpes zoster / varicella zoster virus(VZV)). There will be about 66 participators who will receive two-dose injection at the upper arm. LZ901 vaccine is made up of a tetramer of VZV glycoprotein E (VZV gE-Fc) and adsorbed with aluminum hydroxide adjuvant. This adjuvant can raise the immune response to a lot of antigens. It is the most widely used and safe adjuvant in various types of vaccines worldwide. In this study: The participation is voluntary. Before the study, participants will receive some tests for screening. If qualified, investigators will officially invite them to join this study. The study vaccine is LZ901 with two different dose levels (50μg/0.5 mL, 100μg/0.5 mL). The placebo, which is saline solution, has no active drug. Participants will receive one of three as above mentioned. Participants will be enrolled in one of four cohorts. If participants are enrolled in Cohorts 1 or 2, they will receive LZ901. If participants are enrolled in Cohorts 3 or 4, they will have a 2 out of 3 chance (66%) of receiving LZ901 and 1 out of 3 chance (33%) of receiving placebo. In Cohort 3 and 4, the study staff and participants will not know which study treatment participants will be receiving. However, the study doctor can get this information in case of an emergency. Participants will stay at the clinic for 30 minutes after each vaccination to observe if there are any uncomfortable. This study will last about 8 months and will include about 8 study visits to the clinic. During this period, participants will receive a follow-up phone call and/or email by the study staff to follow the condition closely for safety, and record on diary/contact card. Participants will receive some tests during the study, include safety tests such as physical examination, vital signs measurements, blood tests, urinalysis. Participants will be measured the levels of specific antibodies to see if the vaccine works well. This study is for research purposes only. Participants may not receive any direct benefits from participating in this study but have a chance to be in a study that may help others in the future.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase I Clinical Study to Evaluate Safety and Tolerability of a Recombinant Herpes Zoster Vaccine (LZ901) in Subjects Aged 50 to 70 Years Inclusive

Conditions
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Herpes Zoster, Vaccine-Preventable Diseases

Intervention / Treatment
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* Biological: Low Dose Recombinant Herpes Zoster Vaccine (LZ901)
* Biological: High Dose Recombinant Herpes Zoster Vaccine (LZ901)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females able to provide legal identity certificate, aged 50 to 70 years inclusive at the time of signing the ICF; Able to understand the study procedures, voluntarily agree to participate in the study, and sign the ICF; Subjects are healthy or have well controlled mild medical conditions as determined by the investigator； Female subjects are not pregnant or lactating. Female subjects with childbearing potential* should take reliable contraceptive measures**, and have no pregnancy and fertility plan within 7 months; *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). Post-menopausal should be confirmed with FSH and Estradiol levels. **Reliable, medically acceptable forms of contraception: For 3 months prior to screening - hormonal contraceptive (e.g., oral, patch, injectable, depot or vaginal ring), or implantable device (implantable rod or intrauterine device), or For at least 1 month prior to screening - a double barrier method (e.g., diaphragm, cervical cap, or condom in conjunction with spermicide or sponge), or Subjects of reproductive age that are abstinent are acceptable provided they agree to a double barrier method should they become sexually active during the study. and subjects agree to continue birth control for at least 7 months. Able to attend all scheduled follow-up visits and able to comply with protocol requirements; Oral temperature < 37.5℃/99.5℉. Exclusion Criteria: Subjects with a personal history or family history of convulsion, epilepsy, encephalopathy, and psychosis; Subjects who received immunosuppressive therapy within 3 months before vaccination (e.g., long-term use of systemic glucocorticoids for ≥ 14 days, dose ≥ 2 mg/kg/day or ≥ 20 mg/day prednisone or equivalence); Allergic to any component of the investigational vaccine, or have a history of a severe allergy to any vaccination; Impaired immune function or diagnosed with congenital or acquired immunodeficiency disease, positive serology for Hepatitis B Surface Antigen, Hepatitis C Antibody and human immunodeficiency virus (HIV); History of varicella or herpes zoster vaccination; History of HZ; Received an inactivated or recombinant vaccine within 14 days or any live vaccine within 28 days prior to vaccination; Subjects who have acute diseases within 3 days before vaccination, or acute stage or exacerbation of chronic diseases within 1 month before vaccination; Subjects with tattoos to the upper arm deltoid area or have infectious skin disease; History of thrombocytopenia or other coagulation disorders, which may cause contraindications to intramuscular injection; History of asplenia or functional asplenia, and asplenia or splenectomy due to any condition; Subjects with ≥ Grade 2 laboratory abnormalities and Grade 1 laboratory abnormalities that the investigator consider clinically significant; Participating in other clinical studies of investigational or un-registered products (drugs, vaccines or devices, etc.), or planning to participate in other clinical studies before the end of this clinical study; Any conditions that in the opinion of the investigator may affect subject safety or assessments (disease factors such as extensive psoriasis, unexplained skin rash, eczema, chronic pain syndrome, or social factors such as plans to move elsewhere before the end of the study). A positive screen for alcohol, drugs of abuse at screening period and Day 0 (before vaccination).

Ages Eligible for Study
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Minimum Age: 50 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort1: Low dose sentinel group<br>Three subjects will be first enrolled into low dose sentinel group in open-label, prior to initiation of dosing in each dose level main group. | Biological: Low Dose Recombinant Herpes Zoster Vaccine (LZ901)<br>* 0.5 mL per dose, containing a total of 50 µg recombinant herpes zoster virus glycoprotein E, adjuvanted with alumina adjuvant.<br>|
| Experimental: Cohort2: High dose sentinel group<br>After reviewing the safety through 7 days after the first dose of LZ901, if no safety signals occur, another 3 subjects will be enrolled into high dose sentinel group in open-label. | Biological: High Dose Recombinant Herpes Zoster Vaccine (LZ901)<br>* 0.5 mL per dose, containing a total of 100 µg recombinant herpes zoster virus glycoprotein E, adjuvanted with alumina adjuvant.<br>|
| Placebo Comparator: Cohort3: Low dose main group<br>If also no safety signals occur through 7 days after the first dose of LZ901 in high dose sentinel group, 30 subjects will be randomized in a 2:1 ratio to receive two doses of LZ901 or placebo in a double-blind fashion in low dose main group. | Biological: Low Dose Recombinant Herpes Zoster Vaccine (LZ901)<br>* 0.5 mL per dose, containing a total of 50 µg recombinant herpes zoster virus glycoprotein E, adjuvanted with alumina adjuvant.<br>Drug: Placebo<br>* 0.5 mL per dose, containing 4.5 mg sodium chloride.<br>* Other names: Saline solution;|
| Placebo Comparator: Cohort4: High dose main group<br>Subjects will be enrolled in high dose main group also after the safety review through 7 days after the first dose of LZ901 or placebo in low dose main group. | Biological: High Dose Recombinant Herpes Zoster Vaccine (LZ901)<br>* 0.5 mL per dose, containing a total of 100 µg recombinant herpes zoster virus glycoprotein E, adjuvanted with alumina adjuvant.<br>Drug: Placebo<br>* 0.5 mL per dose, containing 4.5 mg sodium chloride.<br>* Other names: Saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited AEs | A solicited AE is a pre-specified outcome that the subject is asked to record as present or not. The solicited AEs can be classified as vaccination site (local) AEs and Solicited systemic AEs based on the occurrence site. | From Day 0 through Day 6 after each vaccination. | 
| Unsolicited AEs | Unsolicited AEs include all AEs, except solicited AEs reported Days 0 6 after the study intervention. | From Days 0 29 after each vaccination. | 
| AEs leading to withdrawal | The incidence of AEs leading subjects to withdrawal according to criteria for subject treatment discontinuation and withdrawal from study. | From Day 0 until the outcome is clear after the following up, up to the end of study. | 
| SAEs and MAAEs | The incidence of all serious adverse events (SAEs) and medically attended adverse events (MAAEs). | From Day 0 through 6 months after the full course vaccination. | 
| Abnormal laboratory tests results | The incidence of abnormal laboratory tests results. | On Day 3 (+ 1 day) after each study intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seropositivity rate of anti-gE antibody | The percentage of seropositive subjects of anti-gE antibody. | On Day 30 after each study intervention. | 
| The seropositivity rate of anti-VZV antibody | The percentage of seropositive subjects of anti-VZV antibody. | On Day 30 after each study intervention. | 
| Geometric mean concentration (GMC) of anti-gE | Measured by ELISA. | On Day 30 after each study intervention. | 
| Geometric mean titer (GMT) of anti-VZV | Measured by fluorescent antibody to the membrane antigen (FAMA). | On Day 30 after each study intervention. | 
| The seroconversion rate of anti-VZV antibody | Seroconversion refers to at least a 4-fold increase in the anti-VZV antibody titer at the endpoint as compared to the prevaccination concentration (for subjects seropositive pre-vaccination) or a 4-fold increase at the endpoint as compared to the anti-VZV antibody titer cut-off value for seropositivity (for subjects seronegative pre-vaccination). | On Day 30 after each study intervention. | 
| The seroconversion rate of anti-gE antibody | Seroconversion refers to at least a 4-fold increase in the anti-gE Ab concentration at the endpoint as compared to the prevaccination concentration (for subjects seropositive pre-vaccination) or a 4-fold increase at the endpoint as compared to the anti-gE Ab cut-off value for seropositivity (for subjects seronegative pre-vaccination). | On Day 30 after each study intervention. | 
| Change of anti-Fc antibody | Change of anti-Fc antibody on Day 30 after each study intervention compared with pre-immunization. | From pre-immunization to Day 30 after each study intervention. | 

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