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
Overview
- Phase
- Phase 1
- Intervention
- Z-1018
- Conditions
- Shingles
- Sponsor
- Dynavax Technologies Corporation
- Enrollment
- 764
- Locations
- 12
- Primary Endpoint
- Part 1 and Part 2: Percentage of participants with solicited local and systemic post-injection reactions (PIRs)
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to participate; informed consent provided for the study
- •Male or female ≥ 50 years of age (Part 1: 50 through 69 years of age, inclusive; Part 2: ≥ 70 years of age
- •In good health in the opinion of the investigator, based upon medical history, physical examination, and laboratory evaluation
- •Able to comprehend and follow all required trial procedures and be available for all visits scheduled in the trial
- •Seronegative for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) as assessed during Screening
- •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
- •History of HZ
- •Previous vaccination against varicella (chicken pox) or HZ
- •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)
- •Confirmed SARS-CoV-2/COVID-19 infection as assessed during Screening within 7 days of first trial injection.
- •If female of childbearing potential, is pregnant (known before or established at the time of screening), breastfeeding, or planning a pregnancy or to breastfeed
- •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
- •History of sensitivity to any component of the trial vaccines
- •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
Arms & Interventions
Z-1018 A1 (Part 1)
Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85.
Intervention: Z-1018
Z-1018 A2 (Part 1)
Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85.
Intervention: Z-1018
Z-1018 B1(a) (Part 1)
Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 57.
Intervention: Z-1018
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.
Intervention: Z-1018
Z-1018 B1(b) (Part 1)
Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85
Intervention: Z-1018
Z-1018 B2(b) (Part 1)
Participants will receive a dose of Z-1018 by intramuscular (IM) injection on Day 1 and Day 85
Intervention: Z-1018
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.
Intervention: Z-1018
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.
Intervention: Z-1018
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.
Intervention: Z-1018
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.
Intervention: Z-1018
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.
Intervention: Shingrix
Outcomes
Primary Outcomes
Part 1 and Part 2: Percentage of participants with solicited local and systemic post-injection reactions (PIRs)
Time Frame: Up to 7 days following each dose
Solicited local and systemic post-injection reactions (PIRs)
Part 1 and Part 2: Percentage of participants with Adverse events (AEs)
Time Frame: 28 days following each dose
Adverse events (AEs)
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)
Time Frame: Day 1 through 12 months after the last dose of study injection
Serious adverse events (SAEs) Medically-attended adverse events (MAEs) Immune-mediated adverse events of special interest (imAESIs)
Part 2: Vaccine response
Time Frame: 4 weeks after the second study injection
Composite vaccine response rate in glycoprotein E (gE) -specific CD4+ T cells and anti-gE IgG antibodies in the Per Protocol (PP) population
Part 2: Anti-gE IgG antibody concentration
Time Frame: 4 weeks after the second study injection
Geometric mean concentration (GMC) and geometric mean ratio of IgG antibodies to varicella-zoster virus (VZV) antigen-gE in the Per Protocol (PP) population
Secondary Outcomes
- Part 1: GMC of IgG antibodies to VZV antigen-gE 4 weeks after the second study injection(4 weeks after the second study injection)
- Part 1: Geometric mean ratio (GMR) of IgG antibodies to VZV antigen gE(4 weeks after the second study injection)
- Part 1: Geometric mean fold increase (GMFI) of IgG antibodies to VZV antigen gE(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(4 weeks after the second study injection)
- Part 2: VRR for gE-specific CD4+ T cells(4 weeks after second study injection)