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

Primary Purpose

Herpes Zoster, Vaccine-Preventable Diseases

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Low Dose Recombinant Herpes Zoster Vaccine (LZ901)
High Dose Recombinant Herpes Zoster Vaccine (LZ901)
Placebo
Sponsored by
Beijing Luzhu Biotechnology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Herpes Zoster focused on measuring Herpes Zoster, Vaccine

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

  • Frontage Clinical Services, Inc.Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Cohort1: Low dose sentinel group

Cohort2: High dose sentinel group

Cohort3: Low dose main group

Cohort4: High dose main group

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
Unsolicited AEs
Unsolicited AEs include all AEs, except solicited AEs reported Days 0~6 after the study intervention.
AEs leading to withdrawal
The incidence of AEs leading subjects to withdrawal according to criteria for subject treatment discontinuation and withdrawal from study.
SAEs and MAAEs
The incidence of all serious adverse events (SAEs) and medically attended adverse events (MAAEs).
Abnormal laboratory tests results
The incidence of abnormal laboratory tests results.

Secondary Outcome Measures

The seropositivity rate of anti-gE antibody
The percentage of seropositive subjects of anti-gE antibody.
The seropositivity rate of anti-VZV antibody
The percentage of seropositive subjects of anti-VZV antibody.
Geometric mean concentration (GMC) of anti-gE
Measured by ELISA.
Geometric mean titer (GMT) of anti-VZV
Measured by fluorescent antibody to the membrane antigen (FAMA).
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).
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).
Change of anti-Fc antibody
Change of anti-Fc antibody on Day 30 after each study intervention compared with pre-immunization.

Full Information

First Posted
February 9, 2023
Last Updated
March 23, 2023
Sponsor
Beijing Luzhu Biotechnology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05750017
Brief Title
A Study to Evaluate Safety and Tolerability of a Recombinant Herpes Zoster Vaccine
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2023 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
March 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Luzhu Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Herpes Zoster, Vaccine-Preventable Diseases
Keywords
Herpes Zoster, Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort1: Low dose sentinel group
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort2: High dose sentinel group
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort3: Low dose main group
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Cohort4: High dose main group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Low Dose Recombinant Herpes Zoster Vaccine (LZ901)
Intervention Description
0.5 mL per dose, containing a total of 50 µg recombinant herpes zoster virus glycoprotein E, adjuvanted with alumina adjuvant.
Intervention Type
Biological
Intervention Name(s)
High Dose Recombinant Herpes Zoster Vaccine (LZ901)
Intervention Description
0.5 mL per dose, containing a total of 100 µg recombinant herpes zoster virus glycoprotein E, adjuvanted with alumina adjuvant.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline solution
Intervention Description
0.5 mL per dose, containing 4.5 mg sodium chloride.
Primary Outcome Measure Information:
Title
Solicited AEs
Description
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.
Time Frame
From Day 0 through Day 6 after each vaccination.
Title
Unsolicited AEs
Description
Unsolicited AEs include all AEs, except solicited AEs reported Days 0~6 after the study intervention.
Time Frame
From Days 0~29 after each vaccination.
Title
AEs leading to withdrawal
Description
The incidence of AEs leading subjects to withdrawal according to criteria for subject treatment discontinuation and withdrawal from study.
Time Frame
From Day 0 until the outcome is clear after the following up, up to the end of study.
Title
SAEs and MAAEs
Description
The incidence of all serious adverse events (SAEs) and medically attended adverse events (MAAEs).
Time Frame
From Day 0 through 6 months after the full course vaccination.
Title
Abnormal laboratory tests results
Description
The incidence of abnormal laboratory tests results.
Time Frame
On Day 3 (+ 1 day) after each study intervention.
Secondary Outcome Measure Information:
Title
The seropositivity rate of anti-gE antibody
Description
The percentage of seropositive subjects of anti-gE antibody.
Time Frame
On Day 30 after each study intervention.
Title
The seropositivity rate of anti-VZV antibody
Description
The percentage of seropositive subjects of anti-VZV antibody.
Time Frame
On Day 30 after each study intervention.
Title
Geometric mean concentration (GMC) of anti-gE
Description
Measured by ELISA.
Time Frame
On Day 30 after each study intervention.
Title
Geometric mean titer (GMT) of anti-VZV
Description
Measured by fluorescent antibody to the membrane antigen (FAMA).
Time Frame
On Day 30 after each study intervention.
Title
The seroconversion rate of anti-VZV antibody
Description
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).
Time Frame
On Day 30 after each study intervention.
Title
The seroconversion rate of anti-gE antibody
Description
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).
Time Frame
On Day 30 after each study intervention.
Title
Change of anti-Fc antibody
Description
Change of anti-Fc antibody on Day 30 after each study intervention compared with pre-immunization.
Time Frame
From pre-immunization to Day 30 after each study intervention.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frank Lee, MD
Phone
(201) 416-7745
Ext
(201) 416-7753
Email
flee@frontagelab.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sumitha Reddy, MD
Phone
(201) 416-7760
Email
sreddy@frontagelab.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Lee, MD
Organizational Affiliation
Frontage Clinical Services, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Frontage Clinical Services, Inc.
City
Secaucus
State/Province
New Jersey
ZIP/Postal Code
07094
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frank Lee, MD
Phone
201-416-7745
Ext
(201) 416-7753
Email
flee@frontagelab.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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