Safety and Immunogenicity of Recombinant Herpes Zoster Vaccine (CHO Cells) in Healthy Subjects Aged 18 Years and Above

Herpes Zoster Clinical Trial

Official title:

A Phase I, Single Center, Randomized, Blinded, Controlled Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Immunogenicity of Recombinant Herpes Zoster Vaccine (CHO Cells) in Healthy Subjects Aged 18 Years and Above

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05636436
• Other study ID #: MKKCT-100-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 7, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: MAXVAX Biotechnology Limited Liability Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purposes of the study are to evaluate the safety and tolerability of different dose levels of recombinant herpes zoster vaccine (CHO Cells) with 2 doses at 2-month intervals in healthy subjects aged 18 years and older, and to preliminarily explore immunogenicity.

Description:

The clinical trial will be a single-center, randomized, blind, controlled study in which two dose levels of vaccine will be tested in healthy adults aged 18 to 49 years and 50 years and older, with progression from low dose level to high dose level and younger age group to the older age group based on assessment of safety and tolerability. The younger cohort (aged 18 to 49 years) will consist of 60 subjects, 30 per dose level, and these 30 subjects will be randomized into three subgroups, including vaccine group, adjuvant group and normal saline group, with randomization ratio of 2:2:1. The older cohort (aged 50 years and older) will consist of 72 subjects, 36 per dose level, and these 36 subjects will be randomized into four subgroups, including vaccine group, adjuvant group, Shingrix® group and normal saline group, with randomization ratio of 2:2:1:1.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 132
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Permanent residents aged 18 years and above;

2. Subjects voluntarily agree to participate in the study and signed an informed consent;

3. Be able to participate in all scheduled visits and comply with the protocol requirements.

Exclusion Criteria:

1. Axillary temperature>37.0?;

2. History of herpes zoster within 5 years before vaccination;

3. Prior vaccination with chickenpox vaccine or herpes zoster vaccine;

4. Female participant who is pregnant ( urine pregnancy test was positive) or breastfeeding, or has pregnancy plans within 1 year after the last vaccination;

5. Receipt of live vaccine within 28 days, or any other vaccine within 14 days prior to vaccination;

6. Receipt of immunoglobulin or intravenous immunoglobulin within 3 months before vaccination;

7. Acute diseases or acute exacerbation of chronic disease within 3 days before vaccination;

8. A known allergy to any components of the study vaccine (especially allergic to aminoglycoside antibiotics), or history of severe allergy to any previous vaccination;

9. History of convulsions, epilepsy, encephalopathy (such as congenital brain dysplasia, brain trauma, brain tumor, cerebral hemorrhage, cerebral infarction, brain infection disease, nerve tissue damage caused by chemical drug poisoning, etc.) or mental illness and family history;

10. Asplenia or functional asplenia, or splenectomy caused by any condition;

11. Primary or secondary impairment of immune function or diagnosed congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease or other autoimmune diseases;

12. Receipt of immunosuppressive therapy within 3 months before vaccination (such as long-term use of systemic glucocorticoid =14 days, dose =2mg/kg/day or =20mg/day prednisone or equivalent dose), but inhaled, intra-articular and topical steroids are acceptable;

13. Severe cardiovascular disease(eg. Pulmonary heart disease, Pulmonary Edema); Severe liver or kidney disease; or diabetes with complication;

14. History of thrombocytopenia or other coagulation disorders, which may cause intramuscular injection contraindications;

15. Abnormal blood pressure during physical examination before vaccination (systolic pressure = 140 mmHg and/or diastolic pressure = 90 mmHg);

16. Abnormal and clinically significant laboratory test results as determined by the investigator before vaccination;

17. Current or history of alcohol and/or drug abuse;

18. Any condition that, in the opinion the investigator, may affect the safety of the subject or the evaluation of the study results.

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Zoster

Intervention

Biological:
• Low Dose Recombinant Herpes Zoster Vaccine (CHO cells)
0.5 mL per dose, containing a total of 50 µg recombinant varicella zoster virus glycoprotein E, adjuvanted with low dose MA105.
• High Dose Recombinant Herpes Zoster Vaccine (CHO cells)
0.5 mL per dose, containing a total of 50 µg recombinant varicella zoster virus glycoprotein E, adjuvanted with high dose MA105.
• Low dose adjuvant
0.5 mL per dose, containing low dose MA105 adjuvant.
• High dose adjuvant
0.5 mL per dose, containing high dose MA105 adjuvant.
• Positive control
0.5 mL per dose, containing a total of 50 µg recombinant varicella zoster virus glycoprotein E, adjuvanted with AS01B.
• Placebo
0.5 mL per dose, containing 4.5 mg sodium chloride.

Locations

Country	Name	City	State
China	Yanjin District Center for Disease Control and Prevention	Xinxiang	Henan

Sponsors (2)

Lead Sponsor	Collaborator
MAXVAX Biotechnology Limited Liability Company	Henan Center for Disease Control and Prevention

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence and severity of adverse events	Incidence and severity of adverse events within 30 minutes after each vaccination. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Within 30 minutes after each vaccination.
Primary	The incidence and severity of adverse events	Incidence and severity of adverse events within 7 days after each vaccination. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Within 7 days after each vaccination.
Primary	The incidence and severity of adverse events	Incidence and severity of adverse events during Day 8 to 30 after each vaccination. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Day 8 to 30 after each vaccination.
Primary	The incidence and severity of adverse events	Incidence and severity of adverse events within 30 days after each vaccination. The severity of solicited and unsolicited adverse events will be graded from grade 1 to grade 4, other adverse events will be graded from grade 1 to grade 5.	Within 30 days after each vaccination.
Primary	Incidence of abnormal and clinically significant laboratory test results	Laboratory test includes hematology, blood biochemistry and urine analysis.	Day 4 after each vaccination .
Secondary	Incidence of Serious Adverse Event	Incidence of Serious Adverse Event (SAE) from the first vaccination to 12 months after full vaccination.	From the first vaccination to 12 months after full vaccination (From Day 0 to Day 420).
Secondary	Potential Immune Mediated Disorder	Incidence of Potential Immune Mediated Disorder (pIMD) from the first vaccination to 12 months after full vaccination.	From the first vaccination to 12 months after full vaccination (From Day 0 to Day 420).
Secondary	Geometric mean concentration (GMC) of anti-gE antibody and anti-VZV antibody	Measured by ELISA.	Prior to each vaccination (Day 0, Day 60).
Secondary	Geometric mean concentration (GMC) of anti-gE antibody and anti-VZV antibody	Measured by ELISA.	Day 14 after each vaccination (Day 14, Day 74).
Secondary	Geometric mean concentration (GMC) of anti-gE antibody and anti-VZV antibody	Measured by ELISA.	Month 1 after each vaccination (Day 30, Day 90).
Secondary	Geometric mean concentration (GMC) of anti-gE antibody and anti-VZV antibody	Measured by ELISA.	Month 6 and 12 after the second vaccination (Day 240, Day 420).
Secondary	Seroconversion rate of anti-gE antibody and anti-VZV antibody	Seroconversion is defined as a =4 fold rise in antibody concentration compared with baseline for those antibody concentration was =Cut-off value at baseline; or a =4 fold Cut-off value in antibody concentration compared with baseline for those antibody concentration was	Prior to the second vaccination (Day 60).
Secondary	Seroconversion rate of anti-gE antibody and anti-VZV antibody	Seroconversion is defined as a =4 fold rise in antibody concentration compared with baseline for those antibody concentration was =Cut-off value at baseline; or a =4 fold Cut-off value in antibody concentration compared with baseline for those antibody concentration was	Day 14 after each vaccination (Day 14, Day 74).
Secondary	Seroconversion rate of anti-gE antibody and anti-VZV antibody	Seroconversion is defined as a =4 fold rise in antibody concentration compared with baseline for those antibody concentration was =Cut-off value at baseline; or a =4 fold Cut-off value in antibody concentration compared with baseline for those antibody concentration was	Month 1 after each vaccination (Day 30, Day 90).
Secondary	Positive rate of anti-gE antibody and anti-VZV antibody	Positive rate is defined as percentage of subjects with antibody concentration =Cut-off value.	Prior to each vaccination (Day 0, Day 60).
Secondary	Positive rate of anti-gE antibody and anti-VZV antibody	Positive rate is defined as percentage of subjects with antibody concentration =Cut-off value.	Day 14 after each vaccination (Day 14, Day 74).
Secondary	Positive rate of anti-gE antibody and anti-VZV antibody	Positive rate is defined as percentage of subjects with antibody concentration =Cut-off value.	Month 1 after each vaccination (Day 30, Day 90).
Secondary	Positive rate of anti-gE antibody and anti-VZV antibody	Positive rate is defined as percentage of subjects with antibody concentration =Cut-off value.	Month 6 and 12 after the second vaccination (Day 240, Day 420).
Secondary	Geometric mean increase(GMI) of anti-gE antibody and anti-VZV antibody concentration	The antibody concentration prior to the second vaccination compared with that at baseline (Day 0).	Prior to the second vaccination (Day 60).
Secondary	Geometric mean increase(GMI) of anti-gE antibody and anti-VZV antibody concentration	The antibody concentration at Day 14 after each vaccination compared with that at baseline (Day 0).	Day 14 after each vaccination (Day 14, Day 74).
Secondary	Geometric mean increase(GMI) of anti-gE antibody and anti-VZV antibody concentration	The antibody concentration at 1 month after each vaccination compared with that at baseline (Day 0).	Month 1 after each vaccination (Day 30, Day 90)
Secondary	Four-fold increase rate of the anti-gE antibody and anti-VZV antibody concentration	The antibody concentration prior to the second vaccination compared with that at baseline (Day 0).	Prior to the second vaccination (Day 60).
Secondary	Four-fold increase rate of the anti-gE antibody and anti-VZV antibody concentration	The antibody concentration at Day 14 after each vaccination compared with that at baseline (Day 0).	Day 14 after each vaccination (Day 14, Day 74).
Secondary	Four-fold increase rate of the anti-gE antibody and anti-VZV antibody concentration	The antibody concentration at month 1 after each vaccination compared with that at baseline (Day 0).	Month 1 after each vaccination (Day 30, Day 90).
Secondary	Frequency of gE-specific CD4+ T-cells expressing at least 1 Immunological activation marker	The analysis focused on CD4+ T-cells expressing at least 1 immunological activation marker among Interferon gamma (IFN-?), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-a) and CD40 Ligand (CD40L).	Prior to the first vaccination (Day 0).
Secondary	Frequency of gE-specific CD4+ T-cells expressing at least 1 Immunological activation marker	The analysis focused on CD4+ T-cells expressing at least 1 immunological activation marker among Interferon gamma (IFN-?), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-a) and CD40 Ligand (CD40L).	Month 1 after the second vaccination (Day 90).
Secondary	Frequency of gE-specific CD4+ T-cells expressing at least 1 Immunological activation marker	The analysis focused on CD4+ T-cells expressing at least 1 immunological activation marker among Interferon gamma (IFN-?), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-a) and CD40 Ligand (CD40L).	Month 6, 12 after the second vaccination (Day 240, Day 420).
Secondary	Cellular immune response	Cellular immune response is defined as the frequency of gE-specific CD4+ T-cells (expressing at least 1 Immunological activation marker) =2 fold increase compared with baseline for those the frequency of gE-specific CD4+ T-cells =Cut-off value at baseline; or the frequency of gE-specific CD4+ T-cells (expressing at least 1 Immunological activation marker) =Cut-off value for those the frequency of gE-specific CD4+ T-cells	Prior to the first vaccination (Day 0).
Secondary	Cellular immune response	Cellular immune response is defined as the frequency of gE-specific CD4+ T-cells (expressing at least 1 Immunological activation marker) =2 fold increase compared with baseline for those the frequency of gE-specific CD4+ T-cells =Cut-off value at baseline; or the frequency of gE-specific CD4+ T-cells (expressing at least 1 Immunological activation marker) =Cut-off value for those the frequency of gE-specific CD4+ T-cells	Month 1 after the second vaccination (Day 90).
Secondary	Cellular immune response	Cellular immune response is defined as the frequency of gE-specific CD4+ T-cells (expressing at least 1 Immunological activation marker) =2 fold increase compared with baseline for those the frequency of gE-specific CD4+ T-cells =Cut-off value at baseline; or the frequency of gE-specific CD4+ T-cells (expressing at least 1 Immunological activation marker) =Cut-off value for those the frequency of gE-specific CD4+ T-cells	Month 6, 12 after the second vaccination (Day 240, Day 420)