Herpes Zoster
Conditions
Keywords
Shingles
Brief summary
This is a study to evaluate the safety and immunogenicity of V212 vaccine in adults with autoimmune disease, including participants with rheumatoid arthritis, psoriatic arthritis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, and other similar diseases. The primary hypothesis is that vaccination with V212 vaccine will elicit significant VZV-specific immune responses at approximately 28 days after vaccination 4. The statistical criterion for significance requires that the lower bound of the 2-sided 95% confidence interval of the geometric mean fold rise in vaccine recipients is \>1.0.
Interventions
BIOLOGICALV212
V212 viral antigen for HZ
BIOLOGICALPlacebo
Placebo comparator to V212 vaccine
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with an autoimmune disease * Clinically stable disease for at least 30 days before enrollment * Not likely to undergo hematopoietic stem cell transplantation during the study period * Receiving at least one parenteral or oral biologic agent, such as a Tumor Necrosis factor (TNF) alpha inhibitor, or a parenteral or oral non-biologic therapy, at a stable dose for at least 3 months, with no planned or anticipated changes * History of varicella, antibodies to VZV, or residence for at least 30 years in a country with endemic VZV infection, or if participant is less than 30 years old, attended primary or secondary school in a country with endemic VZV infection
Exclusion criteria
* Prior history of Herpes Zoster (shingles) within 1 year before enrollment * Prior varicella or zoster vaccine * Active central nervous system lupus erythematosus requiring therapeutic intervention within 90 days of enrollment * Prior or planned therapy containing rituximab or other anti-Cluster of Differentiation (CD) 20 monoclonal antibodies from 3 months before enrollment through 28 days postdose 4 * Systemic corticosteroid therapy, prednisone, or equivalent over 40 mg daily at the time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) | Baseline and ~28 days after Vaccination 4 (~Day 118) | Serum samples were tested for antibody response using a gpELISA. The GMFR is response at approximately 28 days postdose 4 / response predose on Day 1. |
| GMFR in VZV Antibody Response Measured by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay | Baseline and ~28 days after Vaccination 4 (~Day 118) | Serum samples were tested for activity using a VZV ELISPOT assay. The assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10\^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at \ 28 days after Vaccination 4 / GMC predose on Day 1. |
| Percentage of Participants With a Serious Adverse Event | Up to ~28 days after Vaccination 4 (~Day 118) | 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, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAE was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Up to Day 5 after any vaccination | 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 were erythema, pain, and swelling. The percentage of participants with one or more VRC-prompted injection-site AE was assessed. |
| Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | Up to ~28 days after Vaccination 4 (~Day 118) | 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 HZ-like rashes. The percentage of participants with one or more VRC-prompted systemic AE was assessed. |
| Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | Up to ~28 days after Vaccination 4 (~Day 118) | Elevated temperature is defined as ≥100.4 °F (≥38.0 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed. |
Participant flow
Pre-assignment details
A total of 362 participants were screened and 354 were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| V212 Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. | 292 |
| Placebo Participants received placebo as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose. | 62 |
| Total | 354 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Participant moved | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Screen failure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | V212 | Placebo | Total |
|---|---|---|---|
| Age, Customized 18 to 49 years | 118 Participants | 27 Participants | 145 Participants |
| Age, Customized 50 to 59 years | 89 Participants | 14 Participants | 103 Participants |
| Age, Customized 60 to 69 years | 65 Participants | 12 Participants | 77 Participants |
| Age, Customized 70 to 79 years | 20 Participants | 6 Participants | 26 Participants |
| Age, Customized 80+ years | 0 Participants | 3 Participants | 3 Participants |
| Autoimmune Therapy Regimen: Biologic or Non-biologic Biologic autoimmune therapy regimen | 142 Participants | 28 Participants | 170 Participants |
| Autoimmune Therapy Regimen: Biologic or Non-biologic Non-biologic autoimmune therapy regimen | 150 Participants | 34 Participants | 184 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 9 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 248 Participants | 53 Participants | 301 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 5 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 26 Participants | 8 Participants | 34 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 239 Participants | 49 Participants | 288 Participants |
| Sex: Female, Male Female | 189 Participants | 37 Participants | 226 Participants |
| Sex: Female, Male Male | 103 Participants | 25 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 289 | 0 / 62 |
| other Total, other adverse events | 171 / 289 | 11 / 62 |
| serious Total, serious adverse events | 9 / 289 | 1 / 62 |
Outcome results
Primary
Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA)
Serum samples were tested for antibody response using a gpELISA. The GMFR is response at approximately 28 days postdose 4 / response predose on Day 1.
Time frame: Baseline and ~28 days after Vaccination 4 (~Day 118)
Population: Participants with Day 1 and/or postdose data available. This outcome measure applied only to participants who received V212; placebo participants were not assessed for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V212 | Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) | 1.57 Ratio |
p-value: <0.0001Longitudinal regression
Primary
GMFR in VZV Antibody Response Measured by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay
Serum samples were tested for activity using a VZV ELISPOT assay. The assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10\^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at \ 28 days after Vaccination 4 / GMC predose on Day 1.
Time frame: Baseline and ~28 days after Vaccination 4 (~Day 118)
Population: Participants with Day 1 and/or postdose data available. This outcome measure applied only to participants who received V212; placebo participants were not assessed for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V212 | GMFR in VZV Antibody Response Measured by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay | 2.01 Ratio |
p-value: <0.0001Longitudinal regression
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, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAE was assessed.
Time frame: Up to ~28 days after Vaccination 4 (~Day 118)
Population: All participants who received at least one dose of vaccine and had safety follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V212 | Percentage of Participants With a Serious Adverse Event | 2.8 Percentage of participants |
| Placebo | Percentage of Participants With a Serious Adverse Event | 1.6 Percentage of participants |
Secondary
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 were erythema, pain, and swelling. The percentage of participants with one or more VRC-prompted injection-site AE was assessed.
Time frame: Up to Day 5 after any vaccination
Population: All participants who received at least one dose of vaccine and had safety follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| V212 | Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Injection-site erythema | 46.0 Percentage of participants |
| V212 | Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Injection-site pain | 42.2 Percentage of participants |
| V212 | Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Injection-site swelling | 40.1 Percentage of participants |
| Placebo | Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Injection-site erythema | 1.6 Percentage of participants |
| Placebo | Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Injection-site pain | 14.5 Percentage of participants |
| Placebo | Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | Injection-site swelling | 4.8 Percentage of participants |
Secondary
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 HZ-like rashes. The percentage of participants with one or more VRC-prompted systemic AE was assessed.
Time frame: Up to ~28 days after Vaccination 4 (~Day 118)
Population: All participants who received at least one dose of vaccine and had safety follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V212 | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 51.6 Percentage of participants |
| Placebo | Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card | 46.8 Percentage of participants |
Secondary
Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card
Elevated temperature is defined as ≥100.4 °F (≥38.0 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed.
Time frame: Up to ~28 days after Vaccination 4 (~Day 118)
Population: All participants who received at least one dose of vaccine and had safety follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V212 | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 7.0 Percentage of participants |
| Placebo | Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card | 4.9 Percentage of participants |