Herpes Zoster
Conditions
Brief summary
The study evaluated immunogenicity, safety, and tolerability of ZOSTAVAX™ Vaccine (V211) administered concomitantly versus nonconcomitantly with Quadrivalent Influenza Virus vaccine (inactivated) in participants ≥50 years of age. The primary hypotheses tested 1) the noninferiority of concomitant versus nonconcomitant vaccination with regard to Varicella zoster virus (VZV) Geometric Mean Titer (GMT) antibody responses, 2) the acceptability of geometric mean fold rise in VZV antibody response after concomitant vaccination, and 3) the noninferiority of concomitant versus nonconcomitant vaccination with regard to influenza virus strain-specific GMT antibody responses.
Interventions
BIOLOGICALZOSTAVAX™
A single blinded administration of 0.65 mL subcutaneous injection on Day 1 (concomitant) or at Week 4 (nonconcomitant)
BIOLOGICALPlacebo to ZOSTAVAX™
A single blinded administration of 0.65 mL subcutaneous injection on Day 1 (nonconcomitant) or at Week 4 (concomitant)
BIOLOGICALInfluenza Vaccine
A single open-label administration of 0.5 mL intramuscular injection on Day 1
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 No maximum
Healthy volunteers
Yes
Inclusion criteria
* Has history of varicella or residence in a VZV-endemic area for ≥30 years * Is male, female not of reproductive potential, or female of reproductive potential and has a negative pregnancy test and agrees to avoid becoming pregnant throughout the study
Exclusion criteria
* Has history of hypersensitivity to any vaccine component * Has previously received any varicella or zoster vaccine * Has received an influenza vaccine for the 2015-16 season * Has history of Herpes zoster * Has received immunoglobulin, monoclonal antibodies, or any blood products within 5 months before study vaccination * Is pregnant or breastfeeding, or expecting to conceive during the study * Has used immunosuppressant therapy * Has known or suspected immune dysfunction * Has experienced Guillain-Barré syndrome within 6 weeks * Has severe thrombocytopenia or any other coagulation disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody | Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group) | Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group. |
| Geometric Mean Fold Rise From Baseline in VZV gpELISA Antibody Titers | Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group) | Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group. |
| Geometric Mean Titers of H1N1-specific Influenza Virus Antibody | Baseline and 4 weeks after Influenza vaccination (Week 4) | Antibodies to H1N1-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. |
| Geometric Mean Titers of H3N2-specific Influenza Virus Antibody | Baseline and 4 weeks after Influenza vaccination (Week 4) | Antibodies to H3N2-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. |
| Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody | Baseline and 4 weeks after Influenza vaccination (Week 4) | Antibodies to B-Yamagata-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. |
| Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody | Baseline and 4 weeks after Influenza vaccination (Week 4) | Antibodies to B-Victoria-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. |
Participant flow
Pre-assignment details
A total of 901 participants were screened and 882 were randomized to one of two vaccination groups.
Participants by arm
| Arm | Count |
|---|---|
| Concomitant Vaccination ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4 | 440 |
| Nonconcomitant Vaccination Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4 | 442 |
| Total | 882 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 3 |
Baseline characteristics
| Characteristic | Concomitant Vaccination | Nonconcomitant Vaccination | Total |
|---|---|---|---|
| Age, Continuous | 60.8 Years STANDARD_DEVIATION 7.2 | 61.3 Years STANDARD_DEVIATION 7.7 | 61.0 Years STANDARD_DEVIATION 7.5 |
| Sex: Female, Male Female | 266 Participants | 262 Participants | 528 Participants |
| Sex: Female, Male Male | 174 Participants | 180 Participants | 354 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 256 / 435 | 256 / 438 |
| serious Total, serious adverse events | 4 / 435 | 6 / 438 |
Outcome results
Primary
Geometric Mean Fold Rise From Baseline in VZV gpELISA Antibody Titers
Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group.
Time frame: Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group)
Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Concomitant Vaccination | Geometric Mean Fold Rise From Baseline in VZV gpELISA Antibody Titers | 1.9 Ratio of titers (Week 4 / Baseline) |
| Nonconcomitant Vaccination | Geometric Mean Fold Rise From Baseline in VZV gpELISA Antibody Titers | 2.1 Ratio of titers (Week 4 / Baseline) |
p-value: <0.00195% CI: [1.76, 2.05]Longitudinal regression
Primary
Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody
Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group.
Time frame: Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group)
Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody | Baseline, n=427, 409 | 206.0 gpELISA units/mL |
| Concomitant Vaccination | Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody | Week 4, n=409, 392 | 395.6 gpELISA units/mL |
| Nonconcomitant Vaccination | Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody | Baseline, n=427, 409 | 230.5 gpELISA units/mL |
| Nonconcomitant Vaccination | Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody | Week 4, n=409, 392 | 482.0 gpELISA units/mL |
p-value: <0.00195% CI: [0.8, 0.95]Longitudinal regression model
Primary
Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody
Antibodies to B-Victoria-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Time frame: Baseline and 4 weeks after Influenza vaccination (Week 4)
Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody | Baseline, n=426, 427 | 11.2 Titer |
| Concomitant Vaccination | Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody | Week 4, n=409, 405 | 33.9 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody | Baseline, n=426, 427 | 10.4 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody | Week 4, n=409, 405 | 32.3 Titer |
p-value: <0.00195% CI: [0.87, 1.13]Longitudinal regression
Primary
Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody
Antibodies to B-Yamagata-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Time frame: Baseline and 4 weeks after Influenza vaccination (Week 4)
Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody | Baseline, n=426, 427 | 14.6 Titer |
| Concomitant Vaccination | Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody | Week 4, n=409, 405 | 46.7 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody | Baseline, n=426, 427 | 12.6 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody | Week 4, n=409, 405 | 43.9 Titer |
p-value: <0.00195% CI: [0.88, 1.14]Longitudinal regression
Primary
Geometric Mean Titers of H1N1-specific Influenza Virus Antibody
Antibodies to H1N1-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Time frame: Baseline and 4 weeks after Influenza vaccination (Week 4)
Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers of H1N1-specific Influenza Virus Antibody | Baseline, n=426, 427 | 51.9 Titer |
| Concomitant Vaccination | Geometric Mean Titers of H1N1-specific Influenza Virus Antibody | Week 4, n=409, 405 | 207.3 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of H1N1-specific Influenza Virus Antibody | Baseline, n=426, 427 | 50.1 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of H1N1-specific Influenza Virus Antibody | Week 4, n=409, 405 | 200.5 Titer |
p-value: <0.00195% CI: [0.88, 1.18]Longitudinal regression
Primary
Geometric Mean Titers of H3N2-specific Influenza Virus Antibody
Antibodies to H3N2-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Time frame: Baseline and 4 weeks after Influenza vaccination (Week 4)
Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers of H3N2-specific Influenza Virus Antibody | Baseline, n=426, 427 | 29.5 Titer |
| Concomitant Vaccination | Geometric Mean Titers of H3N2-specific Influenza Virus Antibody | Week 4, n=409, 405 | 298.8 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of H3N2-specific Influenza Virus Antibody | Baseline, n=426, 427 | 31.1 Titer |
| Nonconcomitant Vaccination | Geometric Mean Titers of H3N2-specific Influenza Virus Antibody | Week 4, n=409, 405 | 272.0 Titer |
p-value: <0.00195% CI: [0.94, 1.29]Longitudinal regression