Safety and Immunogenicity of an Investigational Herpes Zoster Vaccine (Z-1018) Compared to Shingrix® in Healthy Adults 50 Years of Age and Over

A Phase 1/2 Randomized, Observer-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 Participants 50 Years of Age and Over

This is a randomized, active-controlled, observer-blinded, dose-escalation multi-center trial of 2 doses of an investigational HZ vaccine (Z-1018) in approximately 764 healthy adults.

Study Overview

• Status: Active, not recruiting
• Conditions: Herpes Zoster; Vaccine-Preventable Diseases; Shingles
• Intervention / Treatment: Biological: Z-1018; Biological: Shingrix

Detailed Description

Part 1 will enroll approximately 440 participants 50 through 69 years of age (YOA) [inclusive] to 1 of 10 arms of Z-1018 or to Shingrix.

Part 2 will enroll approximately 324 participants ≥ 70 YOA to 1 arm of Z-1018 (selected from Part 1) to be administered in a 1:1 randomization ratio with Shingrix. Part 2 only: after completing the 12-month post-vaccination visit, Part 2 participants will be followed for an additional 4 years for immunopersistence and for herpes zoster (HZ) and post herpetic neuralgia (PHN).

• Study Type: Interventional
• Enrollment (Estimated): 764
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Paratus Clinical Research Western Syndney
    • Botany, New South Wales, Australia, 2019
      • Emeritus Research
    • Brookvale, New South Wales, Australia, 2100
      • Canopy Clinical Northern Beaches
    • Kanwal, New South Wales, Australia, 2259
      • Paratus Clinical Research Central Coast
    • Miranda, New South Wales, Australia, 2228
      • Sutherland Shire Clinical Research
    • Waitara, New South Wales, Australia, 2077
      • Innovate Clinical Research
    • Wollongong, New South Wales, Australia, 2500
      • Canopy Clinical Wollongong
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Paratus Clinical Research Brisbane
  • Victoria
    • Bayswater, Victoria, Australia, 3153
      • Veritus Research
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
    • East Melbourne, Victoria, Australia, 3002
      • Doherty Clinical Trials Limited
• New Zealand
  • Auckland, New Zealand, 0632
    • Optimal Clinical Trials Ltd - North
  • Auckland, New Zealand, 1010
    • Optimal Clinical Trials Ltd - Central
  • Christchurch, New Zealand, 8011
    • New Zealand Clinical Research
  • Wellington, New Zealand, 0621
    • Momentum Wellington
  • Wellington, New Zealand, 5036
    • Momentum Clinical Research Kapiti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Willing to participate; informed consent provided for the study
2. Male or female ≥ 50 years of age (Part 1: 50 through 69 years of age, inclusive; Part 2: ≥ 70 years of age
3. In good health in the opinion of the investigator, based upon medical history, physical examination, and laboratory evaluation
4. Able to comprehend and follow all required trial procedures and be available for all visits scheduled in the trial
5. Seronegative for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) as assessed during Screening
6. If female of child-bearing potential and heterosexually active, has practiced adequate contraception for at least 28 days prior to vaccination, has negative pregnancy tests just prior to vaccination, and has agreed to continue adequate contraception through 3 months following the final study injection.

Exclusion Criteria:

1. History of HZ
2. Previous vaccination against varicella (chicken pox) or HZ
3. Febrile illness within 7 days of the first trial injection (defined as at least 1 measured body temperature of ≥ 38°C, regardless of route of measurement)
4. Confirmed SARS-CoV-2/COVID-19 infection as assessed during Screening within 7 days of first trial injection.
5. If female of childbearing potential, is pregnant (known before or established at the time of screening), breastfeeding, or planning a pregnancy or to breastfeed
6. Known or suspected immunodeficiency (including but not limited to HIV/AIDS), or immunocompromised state, as assessed by medical history, past or current laboratory studies, and/or physical examination
7. History of sensitivity to any component of the trial vaccines

8. Has received the following prior to Day 1 trial injection:

   a) ≤ 14 days: i) Any licensed or authorized inactivated vaccines (including vaccines containing mRNA or CpG)

   b) ≤ 28 days: i) Any live vaccine ii) Systemic corticosteroids (≥ 20 mg/ day of prednisone or equivalent for more than 14 consecutive days) or other immunomodulators or immune suppressive medication, with the exception of inhaled steroids iii) Any investigational medicinal agent

   c) ≤ 90 days: i) Granulocyte or granulocyte-macrophage colony-stimulating factor ii) Immunoglobulins or any blood products (receipt of certain monoclonal antibodies may on a case-by-case basis be non-exclusionary if approved via consultation with Sponsor Medical Monitor) iii) Antisense oligonucleotides iv) Drugs/investigational agents with very long half-lives (defined as ≥ 60 days) (eg, radioactive iodine-125, amiodarone, nirsevimab, and evinacumab) v) Infusion of blood products

   d) ≤ 6 months before Day 1 (or likely to require during the trial period): i) chronic administration of immunosuppressants or other immune-modifying drugs

   e) At any time: DNA plasmids or other genetic therapy intended to integrate permanently into host cells

9. Is undergoing chemotherapy or expected to receive chemotherapy during the trial period; and/or has a diagnosis of cancer within the last 5 years other than squamous cell or basal cell carcinoma of the skin
10. History or current evidence of any condition, therapy, laboratory abnormality, or other finding that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
11. Underlying chronic medical condition requiring ongoing follow-up and monitoring by a healthcare provider that might affect the immune response to vaccine (eg, diabetes mellitus, chronic kidney disease)
12. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
13. Current or historical autoimmune disease
14. Any skin condition and/or tattoo on both arms that may interfere with the evaluation of safety at the injection site, in the opinion of the treating investigator
15. Any other finding that the Investigator considers will make the participant unsuitable for the trial or unable to comply with the trial requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Z-1018 A1 (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 A2 (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 B1(a) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 57.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 B2(a) (Part 1 and Part 2); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 57.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 B1(b) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 B2(b) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 Formulation C1(a) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 57.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 Formulation C2(a) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 57.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 Formulation C1(b) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85.	Biological: Z-1018; Formulation for injection
Experimental: Z-1018 Formulation C2(b) (Part 1); Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85.	Biological: Z-1018; Formulation for injection
Experimental: Shingrix (Part 1 and Part 2); Participants will receive a dose of Shingrix by intramuscular (IM) injection on Day 1 and Day 57, or Day 1 and Day 85.	Biological: Shingrix; Formulation for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Percentage of participants with solicited local and systemic post-injection reactions (PIRs)	Solicited local and systemic post-injection reactions (PIRs)	Up to 7 days following each dose
Part 1 and Part 2: Percentage of participants with Adverse events (AEs)	Adverse events (AEs)	28 days following each dose
Part 1 and Part 2: Percentage of participants with serious adverse events (SAEs), medically-attended adverse events (MAEs), and immune-mediated adverse events of special interest (imAESIs)	Serious adverse events (SAEs) Medically-attended adverse events (MAEs) Immune-mediated adverse events of special interest (imAESIs)	Day 1 through 12 months after the last dose of study injection
Part 2: Vaccine response	Composite vaccine response rate in glycoprotein E (gE) -specific CD4+ T cells and anti-gE IgG antibodies in the Per Protocol (PP) population	4 weeks after the second study injection
Part 2: Anti-gE IgG antibody concentration	Geometric mean concentration (GMC) and geometric mean ratio of IgG antibodies to varicella-zoster virus (VZV) antigen-gE in the Per Protocol (PP) population	4 weeks after the second study injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: GMC of IgG antibodies to VZV antigen-gE 4 weeks after the second study injection	GMC to VZV gE in the Per Protocol (PP) population	4 weeks after the second study injection
Part 1: Geometric mean ratio (GMR) of IgG antibodies to VZV antigen gE	Geometric mean ratio (GMR) of IgG antibodies to VZV antigen gE in the Per Protocol (PP) population	4 weeks after the second study injection
Part 1: Geometric mean fold increase (GMFI) of IgG antibodies to VZV antigen gE	Geometric mean fold increase (GMFI) of IgG antibodies to VZV antigen gE in the Per Protocol (PP) population	4 weeks after the second study injection
Part 1 and Part 2: Vaccine response rate (VRR) for anti-gE IgG antibodies to VZV antigen gE	Vaccine response rate (VRR) for anti-gE IgG antibodies to VZV antigen gE in the Per Protocol (PP) population	4 weeks after the second study injection
Part 2: VRR for gE-specific CD4+ T cells	VRR for gE-specific CD4+ T cells in the Per Protocol (PP) population	4 weeks after second study injection

Collaborators and Investigators

• Sponsor: Dynavax Technologies Corporation
• Investigators: Study Chair: Robert Janssen, MD, Dynavax Technologies Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2031

Study Registration Dates

• First Submitted: July 8, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Vaccine-Preventable Diseases; Herpes Zoster
• Other Study ID Numbers: DV2-ZOS-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No