Herpes Zoster
Conditions
Keywords
Herpes Zoster (Shingles)
Brief summary
The purpose of this study was to assess the safety and tolerability of gamma-irradiated varicella-zoster virus (VZV) vaccine A (Part 1) and gamma-irradiated VZV vaccine B and C (Part 2) and to determine if they were immunogenic when administered to healthy individuals, as measured by VZV-specific antibody responses by glycoprotein enzyme-linked immunosorbent assay (gpELISA). The primary hypothesis was that gamma-irradiated VZV vaccine A (Part 1) and gamma-irradiated VZV vaccine B and C (Part 2) would elicit an acceptable VZV-specific immune response. The secondary hypothesis for Part 1 of the study was that heat-treated VZV vaccine would elicit an acceptable VZV-specific immune response.
Interventions
BIOLOGICALComparator: V212
0.65 mL subcutaneous injection of heat-treated Varicella zoster virus (VZV) vaccine or alternative inactivation method VZV vaccine A, B, C; 4-dose regimen administered \ 30 days apart
BIOLOGICALComparator: Placebo
Placebo; 4-dose regimen administered \ 30 days apart.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be 50 to 59 years of age * No fever on vaccination days * Must have had chickenpox or lived in an area where the chickenpox virus is prevalent for 30 or more years * Females of child-bearing potential must use acceptable forms of birth control
Exclusion criteria
* Prior history of shingles * Prior receipt of any chickenpox or shingles vaccine * Pregnant or breastfeeding * Received or expect to receive a live virus vaccine (such as measles, mumps, rubella) from 4 weeks before the first visit through the last visit * Received or expect to receive an inactivated vaccine (such as tetanus or pneumonia) from 7 days before the first visit through the last visit * Received immunoglobulin or blood products * Receiving treatment that may weaken the immune system * Have an immune system disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Geometric Mean Fold Rise of the Varicella-Zoster Virus (VZV)-Specific Immune Responses Measured by Glycoprotein Enzyme-Linked Immunosorbent Assay in Gamma-Irradiated VZV Vaccine A Recipients | Baseline and ~28 days Postdose 4 (~Day 118) | Serum samples were tested for antibody response using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) in gamma-irradiated VZV vaccine A recipients. The geometric mean fold rise (GMFR) is the response at approximately 28 days postdose 4 / response predose on Day 1. This outcome measure applied only to participants who received VZV vaccine A; heat-treated VZV vaccine and placebo participants were not assessed for this outcome. |
| Part 2: Geometric Mean Fold Rise of the VZV-Specific Immune Responses Measured by gpELISA in Gamma-Irradiated VZV Vaccine B Recipients | Baseline and ~28 days Postdose 4 (~Day 118) | Serum samples were tested for antibody response using gpELISA in gamma-irradiated VZV vaccine B recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1. |
| Part 2: Geometric Mean Fold Rise of the VZV-Specific Immune Responses Measured by gpELISA in Gamma-Irradiated VZV Vaccine C Recipients | Baseline and ~28 days Postdose 4 (~Day 118) | Serum samples were tested for antibody response using gpELISA in gamma-irradiated VZV vaccine C recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1. |
| Percentage of Participants With a Serious Adverse Event | Up to ~28 days Postdose 4 (Up to ~118 days) | A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, or is a congenital anomaly or birth defect. The percentage of participants with one or more SAEs was assessed. |
| Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card | Up to Day 5 post any vaccination (Up to ~5 days) | An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Vaccination Report Card (VRC)-prompted injection-site AEs included redness, swelling, and pain/tenderness/soreness. The percentage of participants with one or more VRC prompted injection-site AE was assessed with incidence \> 0% in one or more vaccination groups. |
| Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | Up to ~28 days Postdose 4 (Up to ~118 days) | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. VRC-prompted systemic AEs included non-injection-site varicella-like and herpes zoster (HZ)-like rashes. The percentage of participants with one or more VRC-prompted systemic AE was assessed with incidence \> 0% in one or more vaccination groups. |
| Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | Up to ~28 days Postdose 4 (Up to ~118 days) | Elevated temperature is defined as ≥100.5 °F (≥38.1 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed. |
| Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event | Up to Dose 4 (Up to ~90 days) | An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. The percentage of participants who discontinued the study drug due to one or more AEs was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Geometric Mean Fold Rise of the Heat-Treated VZV-Specific Immune Responses Measured by gpELISA | Baseline and ~28 days Postdose 4 (~Day 118) | Serum samples were tested for antibody response using gpELISA in heat-treated VZV vaccine recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1. |
Participant flow
Recruitment details
The study was performed in 2 parts - Part 1 and Part 2, with a total of 160 participants.
Pre-assignment details
In Part 1, all participants received heat-treated varicella zoster virus (VZV) vaccine, gamma-irradiated VZV vaccine A or placebo administered as a 4-dose regimen approximately every 30 days. In Part 2, all participants received either gamma-irradiated VZV vaccine B or C administered as a 4-dose regimen approximately every 30 days.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Heat-treated Varicella-Zoster Virus (VZV) Vaccine Participants received an 0.65 mL subcutaneous injection of heat-treated VZV vaccine A; 4-dose regimen administered \
30 days apart. | 65 |
| Part 1: Gamma-Irradiated VZV Vaccine A Participants received an 0.65 mL subcutaneous injection of alternative inactivation method VZV vaccine A; 4-dose regimen administered \
30 days apart. | 63 |
| Part 1: Placebo Participants received a 4-dose placebo regimen administered \
30 days apart. | 33 |
| Part 2: Gamma-Irradiated VZV Vaccine B Participants received an 0.65 mL subcutaneous injection of alternative inactivation method VZV vaccine B; 4-dose regimen administered \
30 days apart. | 64 |
| Part 2: Gamma-Irradiated VZV Vaccine C Participants received an 0.65 mL subcutaneous injection of alternative inactivation method VZV vaccine C; 4-dose regimen administered \
30 days apart. | 65 |
| Total | 290 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 4 | 3 |
Baseline characteristics
| Characteristic | Part 1: Heat-treated Varicella-Zoster Virus (VZV) Vaccine | Part 1: Gamma-Irradiated VZV Vaccine A | Part 1: Placebo | Part 2: Gamma-Irradiated VZV Vaccine B | Part 2: Gamma-Irradiated VZV Vaccine C | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.0 Years STANDARD_DEVIATION 2.6 | 54.0 Years STANDARD_DEVIATION 2.5 | 54.0 Years STANDARD_DEVIATION 2.9 | 53.9 Years STANDARD_DEVIATION 3 | 54.6 Years STANDARD_DEVIATION 3.1 | 54.1 Years STANDARD_DEVIATION 2.8 |
| Sex: Female, Male Female | 44 Participants | 45 Participants | 25 Participants | 42 Participants | 37 Participants | 193 Participants |
| Sex: Female, Male Male | 21 Participants | 18 Participants | 8 Participants | 22 Participants | 28 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 61 | 0 / 32 | 0 / 63 | 0 / 65 |
| other Total, other adverse events | 47 / 64 | 48 / 61 | 20 / 32 | 47 / 63 | 43 / 65 |
| serious Total, serious adverse events | 0 / 64 | 1 / 61 | 0 / 32 | 1 / 63 | 0 / 65 |
Outcome results
Primary
Part 1: Geometric Mean Fold Rise of the Varicella-Zoster Virus (VZV)-Specific Immune Responses Measured by Glycoprotein Enzyme-Linked Immunosorbent Assay in Gamma-Irradiated VZV Vaccine A Recipients
Serum samples were tested for antibody response using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) in gamma-irradiated VZV vaccine A recipients. The geometric mean fold rise (GMFR) is the response at approximately 28 days postdose 4 / response predose on Day 1. This outcome measure applied only to participants who received VZV vaccine A; heat-treated VZV vaccine and placebo participants were not assessed for this outcome.
Time frame: Baseline and ~28 days Postdose 4 (~Day 118)
Population: The analysis population included all gamma-irradiated VZV vaccine A participants who received all 4 vaccinations with no protocol deviations; heat-treated VZV vaccine, vaccine B, vaccine C and placebo participants were not assessed for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Part 1: Geometric Mean Fold Rise of the Varicella-Zoster Virus (VZV)-Specific Immune Responses Measured by Glycoprotein Enzyme-Linked Immunosorbent Assay in Gamma-Irradiated VZV Vaccine A Recipients | 2.18 Ratio |
p-value: <0.0001Longitudinal regression (LR)
Primary
Part 2: Geometric Mean Fold Rise of the VZV-Specific Immune Responses Measured by gpELISA in Gamma-Irradiated VZV Vaccine B Recipients
Serum samples were tested for antibody response using gpELISA in gamma-irradiated VZV vaccine B recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1.
Time frame: Baseline and ~28 days Postdose 4 (~Day 118)
Population: The analysis population included all gamma-irradiated VZV vaccine B participants who received all 4 vaccinations with no protocol deviations; heat-treated VZV vaccine, vaccine A, vaccine C and placebo participants were not assessed for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Part 2: Geometric Mean Fold Rise of the VZV-Specific Immune Responses Measured by gpELISA in Gamma-Irradiated VZV Vaccine B Recipients | 1.90 Ratio |
p-value: <0.0001Longitudinal regression (LR)
Primary
Part 2: Geometric Mean Fold Rise of the VZV-Specific Immune Responses Measured by gpELISA in Gamma-Irradiated VZV Vaccine C Recipients
Serum samples were tested for antibody response using gpELISA in gamma-irradiated VZV vaccine C recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1.
Time frame: Baseline and ~28 days Postdose 4 (~Day 118)
Population: The analysis population included all gamma-irradiated VZV vaccine C participants who received all 4 vaccinations and had no protocol deviations; heat-treated VZV vaccine, vaccine A, vaccine B and placebo participants were not assessed for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Part 2: Geometric Mean Fold Rise of the VZV-Specific Immune Responses Measured by gpELISA in Gamma-Irradiated VZV Vaccine C Recipients | 1.58 Ratio |
p-value: <0.0001Longitudinal regression (LR)
Primary
Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. The percentage of participants who discontinued the study drug due to one or more AEs was assessed.
Time frame: Up to Dose 4 (Up to ~90 days)
Population: The analysis population included all participants who received at least one dose of vaccine and who had any safety follow-up based on the actual vaccination received. Participants were excluded if they received an incorrect vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event | 0.0 Percentage of Participants |
| Part 1: Gamma-Irradiated VZV Vaccine A | Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event | 0.0 Percentage of Participants |
| Part 1: Placebo | Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event | 0.0 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine B | Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event | 1.6 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine C | Percentage of Participants Who Discontinued the Study Drug Due to an Adverse Event | 0.0 Percentage of Participants |
95% CI: [-10.8, 5.7]
95% CI: [-10.8, 6]
Primary
Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Vaccination Report Card (VRC)-prompted injection-site AEs included redness, swelling, and pain/tenderness/soreness. The percentage of participants with one or more VRC prompted injection-site AE was assessed with incidence \> 0% in one or more vaccination groups.
Time frame: Up to Day 5 post any vaccination (Up to ~5 days)
Population: The analysis population included all participants who received at least one dose of vaccine and who had any safety follow-up based on the actual vaccination received. Participants were excluded if they received an incorrect vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card | 57.8 Percentage of Participants |
| Part 1: Gamma-Irradiated VZV Vaccine A | Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card | 62.3 Percentage of Participants |
| Part 1: Placebo | Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card | 21.9 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine B | Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card | 63.5 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine C | Percentage of Participants With an Injection-Site Adverse Event Prompted on the Vaccination Report Card | 50.8 Percentage of Participants |
p-value: <0.00195% CI: [15.2, 52.6]Miettinen & Nurminen
p-value: <0.00195% CI: [19.6, 57]Miettinen & Nurminen
Primary
Percentage of Participants With a Serious Adverse Event
A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, or is a congenital anomaly or birth defect. The percentage of participants with one or more SAEs was assessed.
Time frame: Up to ~28 days Postdose 4 (Up to ~118 days)
Population: The analysis population included all participants who received at least one dose of vaccine and who had any safety follow-up based on the actual vaccination received. Participants were excluded if they received an incorrect vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Percentage of Participants With a Serious Adverse Event | 0.0 Percentage of Participants |
| Part 1: Gamma-Irradiated VZV Vaccine A | Percentage of Participants With a Serious Adverse Event | 1.6 Percentage of Participants |
| Part 1: Placebo | Percentage of Participants With a Serious Adverse Event | 0.0 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine B | Percentage of Participants With a Serious Adverse Event | 1.6 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine C | Percentage of Participants With a Serious Adverse Event | 0.0 Percentage of Participants |
95% CI: [-10.8, 5.7]
95% CI: [-9.2, 8.8]
Primary
Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. VRC-prompted systemic AEs included non-injection-site varicella-like and herpes zoster (HZ)-like rashes. The percentage of participants with one or more VRC-prompted systemic AE was assessed with incidence \> 0% in one or more vaccination groups.
Time frame: Up to ~28 days Postdose 4 (Up to ~118 days)
Population: The analysis population included all participants who received at least one dose of vaccine and who had any safety follow-up based on the actual vaccination received. Participants were excluded if they received an incorrect vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 45.3 Percentage of Participants |
| Part 1: Gamma-Irradiated VZV Vaccine A | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 54.1 Percentage of Participants |
| Part 1: Placebo | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 50.0 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine B | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 52.4 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine C | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 41.5 Percentage of Participants |
95% CI: [-25.3, 16.1]
95% CI: [-16.9, 24.9]
Primary
Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card
Elevated temperature is defined as ≥100.5 °F (≥38.1 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed.
Time frame: Up to ~28 days Postdose 4 (Up to ~118 days)
Population: The analysis population included all participants who received at least one dose of vaccine and who had any safety follow-up based on the actual vaccination received. Participants were excluded if they received an incorrect vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 1.6 Percentage of Participants |
| Part 1: Gamma-Irradiated VZV Vaccine A | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 1.6 Percentage of Participants |
| Part 1: Placebo | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 0.0 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine B | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 3.2 Percentage of Participants |
| Part 2: Gamma-Irradiated VZV Vaccine C | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 1.5 Percentage of Participants |
p-value: 0.4895% CI: [-9.3, 8.4]Miettinen & Nurminen
p-value: 0.46995% CI: [-9.2, 8.8]Miettinen & Nurminen
Secondary
Part 1: Geometric Mean Fold Rise of the Heat-Treated VZV-Specific Immune Responses Measured by gpELISA
Serum samples were tested for antibody response using gpELISA in heat-treated VZV vaccine recipients. The GMFR is the response at approximately 28 days postdose 4 / response predose on Day 1.
Time frame: Baseline and ~28 days Postdose 4 (~Day 118)
Population: The analysis population included all heat-treated VZV vaccine participants who received all 4 vaccinations and had no protocol deviations; vaccine A, vaccine B, vaccine C and placebo participants were not assessed for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Gamma- Irradiated VZV Vaccine A | Part 1: Geometric Mean Fold Rise of the Heat-Treated VZV-Specific Immune Responses Measured by gpELISA | 2.10 Ratio |
p-value: <0.0001Longitudinal data analysis (LDA)