Clinical trial NCT05750017: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Herpes Zoster
Vaccine-Preventable Diseases
Keywords: Herpes Zoster
Vaccine
Lead sponsor: Beijing Luzhu Biotechnology Co., Ltd.
Sponsor class: OTHER
First posted: 2023-03-01
Enrollment: 66
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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:

1. The participation is voluntary.
2. Before the study, participants will receive some tests for screening. If qualified, investigators will officially invite them to join this study.
3. 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.
4. 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.
5. 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.
6. Participants will stay at the clinic for 30 minutes after each vaccination to observe if there are any uncomfortable.
7. 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.
8. 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.


Eligibility criteria: Inclusion Criteria:

1. Males and females able to provide legal identity certificate, aged 50 to 70 years inclusive at the time of signing the ICF;
2. Able to understand the study procedures, voluntarily agree to participate in the study, and sign the ICF;
3. Subjects are healthy or have well controlled mild medical conditions as determined by the investigator；
4. 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.
5. Able to attend all scheduled follow-up visits and able to comply with protocol requirements;
6. Oral temperature \< 37.5℃/99.5℉.

Exclusion Criteria:

1. Subjects with a personal history or family history of convulsion, epilepsy, encephalopathy, and psychosis;
2. 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);
3. Allergic to any component of the investigational vaccine, or have a history of a severe allergy to any vaccination;
4. 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);
5. History of varicella or herpes zoster vaccination;
6. History of HZ;
7. Received an inactivated or recombinant vaccine within 14 days or any live vaccine within 28 days prior to vaccination;
8. Subjects who have acute diseases within 3 days before vaccination, or acute stage or exacerbation of chronic diseases within 1 month before vaccination;
9. Subjects with tattoos to the upper arm deltoid area or have infectious skin disease;
10. History of thrombocytopenia or other coagulation disorders, which may cause contraindications to intramuscular injection;
11. History of asplenia or functional asplenia, and asplenia or splenectomy due to any condition;
12. Subjects with ≥ Grade 2 laboratory abnormalities and Grade 1 laboratory abnormalities that the investigator consider clinically significant;
13. 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;
14. 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).
15. A positive screen for alcohol, drugs of abuse at screening period and Day 0 (before vaccination).

Primary outcomes:
measure: Solicited AEs
timeFrame: From Day 0 through Day 6 after each vaccination.
measure: Unsolicited AEs
timeFrame: From Days 0~29 after each vaccination.
measure: AEs leading to withdrawal
timeFrame: From Day 0 until the outcome is clear after the following up, up to the end of study.
measure: SAEs and MAAEs
timeFrame: From Day 0 through 6 months after the full course vaccination.
measure: Abnormal laboratory tests results
timeFrame: On Day 3 (+ 1 day) after each study intervention.
Secondary outcomes:
measure: The seropositivity rate of anti-gE antibody
timeFrame: On Day 30 after each study intervention.
measure: The seropositivity rate of anti-VZV antibody
timeFrame: On Day 30 after each study intervention.
measure: Geometric mean concentration (GMC) of anti-gE
timeFrame: On Day 30 after each study intervention.
measure: Geometric mean titer (GMT) of anti-VZV
timeFrame: On Day 30 after each study intervention.
measure: The seroconversion rate of anti-VZV antibody
timeFrame: On Day 30 after each study intervention.
measure: The seroconversion rate of anti-gE antibody
timeFrame: On Day 30 after each study intervention.
measure: Change of anti-Fc antibody
timeFrame: From pre-immunization to Day 30 after each study intervention.
Other outcomes:
Locations:
city: Secaucus
country: United States
facility: Frontage Clinical Services, Inc.
state: New Jersey
Study officials:
affiliation: Frontage Clinical Services, Inc.
name: Frank Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: