Herpes Zoster
Conditions
Keywords
immunology
Brief summary
The study plans to learn more about how the shingles vaccine, Shingrix (SRX), successfully prevents shingles in older people. Two vaccines are currently approved by the Food and Drug Administration (FDA) to prevent shingles. Zostavax is a live virus vaccine which has been available since 2006 and prevents shingles about 50% of the time, though it is less effective the older a person is when they receive it. Shingrix, which was approved by the FDA in 2017, is not a live virus, but has an additive in the vaccine to boost immune response. It is about 97% effective at preventing shingles regardless of a person's age and so far has been effective for at least 4 years after vaccination. Because Zostavax has live virus in it, giving a challenge dose of Zostavax - vOka varicella zoster virus - to people who have received both vaccines (Zostavax or Shingrix) in the past, will allow researchers to learn more about how the body works to prevent shingles and how any shingles vaccination helps protect against shingles.
Detailed description
The primary endpoint of this study was the area under the concentration/time curve of quantitative VZV DNA in plasma. However, all the VZV DNA measurements were below the lower limit of quantitation of the assay. Due to this unexpected outcome, we performed a qualitative analysis of presence or absence of VZV DNA in plasma at Day ≥3 after the vOka challenge.
Interventions
BIOLOGICALZostavax
Intradermal injection of Zostavax
BIOLOGICALShingrix
Given to subjects in Arm 4 who've never had a herpes zoster vaccine
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 50-85 * General good health * Women of non-childbearing potential must be postmenopausal or have undergone hysterectomy or bilateral oophorectomy * ARM 1 ONLY: Documented evidence of immunization with ZVL or SRX at least 5 years previously * ARM 2 ONLY; Documented evidence of immunization with ZVL 6-12 months prior to enrollment * ARM 3 ONLY: Have never received any shingles vaccination
Exclusion criteria
* Prior history of herpes zoster (HZ) * Blood products received in the 3 months prior to study enrollment or planned for the subsequent week for Arm 1; Arm 2 requires same exclusion; Arm 3 extends the exclusion to the week after the vOka challenge, which is 6 months after completing SRX administration. * Significant immune suppressive illness or therapy * Concomitant vaccine received within 2 (inactive) or 4 (live) weeks prior to the study or during the first week of the study. * Women of childbearing potential. * Pregnancy or breastfeeding. * Participation in a concurrent clinical study in which the subject will be exposed to and investigational product during the period starting 7 days before the first dose of study vaccine through the completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of Varicella-Zoster Virus (VZV) DNAemia | Until VZV DNA is undetectable in the blood, measured up to Day 7 | Varicella-Zoster Virus (VZV) DNAemia will be measured by polymerase chain reaction (PCR) as a surrogate for viremia over the first 7 days after vOka intradermal (ID) challenge. The outcome measure will be the area under the concentration time curve of the VZV DNAemia expressed in DNA copies/ml of blood. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ZVL >5 Years Previously (Cohort 1) Participants have received Zostavax (ZVL) at least 5 years previously. Will be administered intradermal vOka varicella zoster virus (ZVL) in non-dominant deltoid. A skin biopsy will be performed at the injection site on 20 subjects.
Zostavax: Intradermal injection of Zostavax | 18 |
| ZVL 6-12 Months Previously (Cohort 3) Participants who received ZVL 6-12 months previously will be administered an intradermal dose of vOka varicella zoster virus (ZVL) in non-dominant deltoid.
Zostavax: Intradermal injection of Zostavax | 32 |
| No Previous ZVL (Cohort 4 Participants who've never received a shingles vaccine will be given the 2 standard doses of RZV. Six months later they will be given the intradermal dose of vOka varicella zoster virus (ZVL) in the non-dominant deltoid.
Zostavax: Intradermal injection of Zostavax
Shingrix: Given to subjects in Arm 4 who've never had a herpes zoster vaccine | 35 |
| SRX >5 Years Previously (Cohort 2) Participants have received Shingrix at least 5 years previously. Will be administered intradermal vOka varicella zoster virus (ZVL) in non-dominant deltoid. A skin biopsy will be performed at the injection site on 20 subjects.
Zostavax: Intradermal injection of Zostavax | 20 |
| Total | 105 |
Baseline characteristics
| Characteristic | ZVL >5 Years Previously (Cohort 1) | ZVL 6-12 Months Previously (Cohort 3) | No Previous ZVL (Cohort 4 | SRX >5 Years Previously (Cohort 2) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 2 Participants | 7 Participants | 11 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 30 Participants | 28 Participants | 9 Participants | 78 Participants |
| Age, Continuous | 65.14 years | 56.37 years | 61.15 years | 67.79 years | 60.74 years |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 1 Participants | 5 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 16 Participants | 25 Participants | 33 Participants | 18 Participants | 92 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 18 participants | 32 participants | 35 participants | 20 participants | 104 participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 25 Participants | 12 Participants | 66 Participants |
| Sex: Female, Male Male | 4 Participants | 17 Participants | 10 Participants | 8 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 32 | 0 / 35 | 0 / 20 |
| other Total, other adverse events | 0 / 18 | 0 / 32 | 16 / 35 | 1 / 20 |
| serious Total, serious adverse events | 0 / 18 | 0 / 32 | 0 / 35 | 0 / 20 |
Outcome results
Primary
Magnitude of Varicella-Zoster Virus (VZV) DNAemia
Varicella-Zoster Virus (VZV) DNAemia will be measured by polymerase chain reaction (PCR) as a surrogate for viremia over the first 7 days after vOka intradermal (ID) challenge. The outcome measure will be the area under the concentration time curve of the VZV DNAemia expressed in DNA copies/ml of blood.
Time frame: Until VZV DNA is undetectable in the blood, measured up to Day 7
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ZVL >5 Years Previously (Cohort 1) | Magnitude of Varicella-Zoster Virus (VZV) DNAemia | NA DNA copies per/mL |
| ZVL 6-12 Months Previously (Cohort 3) | Magnitude of Varicella-Zoster Virus (VZV) DNAemia | NA DNA copies per/mL |
| No Previous ZVL (Cohort 4 | Magnitude of Varicella-Zoster Virus (VZV) DNAemia | NA DNA copies per/mL |
| SRX >5 Years Previously (Cohort 2) | Magnitude of Varicella-Zoster Virus (VZV) DNAemia | NA DNA copies per/mL |