Trial to Evaluate the Safety, Tolerability, and Immunogenicity of an Investigational Herpes Zoster Vaccine (Z-1018) Compared to Shingrix® in Healthy Adult Volunteers

Study Overview
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Brief Summary
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This is a randomized, active-controlled, dose-escalation multi-center study of 2 doses (Day 1 and Week 8) of an investigational herpes zoster (HZ) vaccine (Z-1018), combining herpes zoster antigen- (gE) with a Toll-like receptor 9 (TLR9) agonist adjuvant (CpG 1018) with and without alum in approximately 150 healthy volunteers 50 to 69 years of age (inclusive).

Official Title
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A Phase 1 Randomized, Subject-Blinded, Active-Controlled, Dose Escalation, Multicenter Trial to Evaluate the Safety, Tolerability, and Immunogenicity of an Investigational Herpes Zoster Vaccine (Z-1018) Compared to Shingrix® in Healthy Adult Volunteers Between the Ages of 50 and 69 Years

Conditions
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Shingles, Herpes Zoster, Vaccine-Preventable Diseases

Intervention / Treatment
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* Biological: Z-1018
* Biological: Z-1018
* Biological: Z-1018
* Biological: Z-1018
* Biological: Shingrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 50 to 69 years of age Be in good health in the opinion of the investigator, based upon medical history, physical examination, and laboratory evaluation Must be able to comprehend and follow all required study procedures and be available for all visits scheduled in the study Seronegative for human immunodeficiency virus (HIV) Exclusion Criteria: History of HZ Previous vaccination against varicella or HZ If female of childbearing potential, is pregnant, breastfeeding, or planning a pregnancy Known history of HIV (HIV 1/2 antibodies) Has a history of sensitivity to any component of study vaccines Has received any blood products or immunoglobulin within 90 days prior to study injection, or is likely to require infusion of blood products during the study period Has received the following prior to the first injection: 14 days: any non-live vaccine 28 days: Any live vaccine, including a COVID-19 vaccine Systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication, with the exception of inhaled steroids Granulocyte or granulocyte-macrophage colony-stimulating factor Any other investigational medicinal agent, including a COVID-19 vaccine Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose Is undergoing chemotherapy or expected to receive chemotherapy during the study period; has a diagnosis of cancer within the last 5 years other than squamous cell or basal cell carcinoma of the skin History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator History of autoimmune disease

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Z-1018 Dose Level 1<br>100 mcg gE + 3000 mcg CpG 1018 | Biological: Z-1018<br>* contains gE at a dose of 100 mcg to be combined with a Toll-like receptor 9 agonist adjuvant, CpG 1018 at dose of 3000 mcg<br>|
| Experimental: Z-1018 Dose Level 1a<br>100 mcg gE + 3000 mcg CpG 1018 + alum | Biological: Z-1018<br>* contains gE at a dose of 100 mcg to be combined with a Toll-like receptor 9 agonist adjuvant, CpG 1018 at dose of 3000 mcg with aluminum hydroxide (alum)<br>|
| Experimental: Z-1018 Dose Level 2<br>100 mcg gE + 6000 mcg CpG 1018 | Biological: Z-1018<br>* contains gE at a dose of 100 mcg to be combined with a Toll-like receptor 9 agonist adjuvant, CpG 1018 at dose of 6000 mcg<br>|
| Experimental: Z-1018 Dose Level 2a<br>100 mcg gE + 6000 mcg CpG 1018 + alum | Biological: Z-1018<br>* contains gE at a dose of 100 mcg to be combined with a Toll-like receptor 9 agonist adjuvant, CpG 1018 at dose of 6000 mcg, with aluminum hydroxide (alum)<br>|
| Active Comparator: Shingrix<br> | Biological: Shingrix<br>* a suspension for injection supplied as a single-dose vial of 50 mcg varicella zoster virus (VZV) glycoprotein E (gE) antigen and AS01B adjuvant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of solicited local and systemic post-injection reactions (PIRs) 7 days after administration of study vaccine |  | Day 1 to day 7 | 
| Frequency of solicited local and systemic post-injection reactions (PIRs) 7 days after administration of study vaccine. |  | Day 57 to day 63 | 
| Number of AEs (Adverse Events) |  | Day 1 through week 20 | 
| Number of SAEs (Serious Adverse Events) |  | Through week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of CD4+ T cells |  | At week 12 | 
| Measure Geometric mean concentration (GMC) of IgG antibodies to varicella-zoster virus (VZV) antigen glycoprotein E (gE) |  | At week 12 | 
| Response rate of vaccine |  | At week 12 |