Trial Outcomes & Findings for A Study to Evaluate the Safety and Immunogenicity of Inactivated Varicella Zoster Virus (VZV) Vaccine in Adults With Autoimmune Disease (V212-009) (NCT NCT01527383)
NCT ID: NCT01527383
Last Updated: 2019-01-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
354 participants
Primary outcome timeframe
Baseline and ~28 days after Vaccination 4 (~Day 118)
Results posted on
2019-01-14
Participant Flow
A total of 362 participants were screened and 354 were enrolled.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
292
|
62
|
|
Overall Study
Vaccination 1 (Day 1)
|
291
|
62
|
|
Overall Study
Vaccination 2 (~Day 30)
|
283
|
61
|
|
Overall Study
Vaccination 3 (~Day 60)
|
278
|
58
|
|
Overall Study
Vaccination 4 (~Day 90)
|
277
|
58
|
|
Overall Study
COMPLETED
|
277
|
58
|
|
Overall Study
NOT COMPLETED
|
15
|
4
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
0
|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
|
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
Participant moved
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
Baseline Characteristics
A Study to Evaluate the Safety and Immunogenicity of Inactivated Varicella Zoster Virus (VZV) Vaccine in Adults With Autoimmune Disease (V212-009)
Baseline characteristics by cohort
| Measure |
V212
n=292 Participants
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.
|
Placebo
n=62 Participants
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.
|
Total
n=354 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to 49 years
|
118 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Age, Customized
50 to 59 years
|
89 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
|
Age, Customized
60 to 69 years
|
65 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Age, Customized
70 to 79 years
|
20 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Age, Customized
80+ years
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
189 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
226 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
103 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
128 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
43 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
248 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
301 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
23 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
239 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
288 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
26 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Autoimmune Therapy Regimen: Biologic or Non-biologic
Biologic autoimmune therapy regimen
|
142 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
170 Participants
n=5 Participants
|
|
Autoimmune Therapy Regimen: Biologic or Non-biologic
Non-biologic autoimmune therapy regimen
|
150 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
184 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
V212
n=176 Participants
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.
|
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.
|
|---|---|---|
|
Geometric Mean Fold Rise (GMFR) in Varicella-Zoster (VZV) Antibody Responses Measured by Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA)
|
1.57 Ratio
Interval 1.44 to 1.72
|
—
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
V212
n=176 Participants
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.
|
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.
|
|---|---|---|
|
GMFR in VZV Antibody Response Measured by VZV Interferon-gamma (IFN-g) Enzyme-linked Immunospot (ELISPOT) Assay
|
2.01 Ratio
Interval 1.57 to 2.58
|
—
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
V212
n=289 Participants
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.
|
Placebo
n=62 Participants
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.
|
|---|---|---|
|
Percentage of Participants With a Serious Adverse Event
|
2.8 Percentage of participants
|
1.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 5 after any vaccinationPopulation: All participants who received at least one dose of vaccine and had safety follow-up
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.
Outcome measures
| Measure |
V212
n=289 Participants
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.
|
Placebo
n=62 Participants
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.
|
|---|---|---|
|
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card
Injection-site erythema
|
46.0 Percentage of participants
|
1.6 Percentage of participants
|
|
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card
Injection-site pain
|
42.2 Percentage of participants
|
14.5 Percentage of participants
|
|
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card
Injection-site swelling
|
40.1 Percentage of participants
|
4.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
V212
n=289 Participants
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.
|
Placebo
n=62 Participants
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.
|
|---|---|---|
|
Percentage of Participants With a Systemic Adverse Event Prompted on the Vaccination Report Card
|
51.6 Percentage of participants
|
46.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 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
Elevated temperature is defined as ≥100.4 °F (≥38.0 °C), oral equivalent. The percentage of participants with VRC-prompted elevated temperature was assessed.
Outcome measures
| Measure |
V212
n=284 Participants
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.
|
Placebo
n=61 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Elevated Temperature Prompted on the Vaccination Report Card
|
7.0 Percentage of participants
|
4.9 Percentage of participants
|
Adverse Events
V212
Serious events: 9 serious events
Other events: 171 other events
Deaths: 1 deaths
Placebo
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
V212
n=289 participants at risk
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.
|
Placebo
n=62 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia haemolytic autoimmune
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Eye disorders
Keratitis
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Infections and infestations
Pneumonia
|
0.69%
2/289 • Number of events 2 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/289 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
1.6%
1/62 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Infections and infestations
Urinary tract infection
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Vascular disorders
Deep vein thrombosis
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Nervous system disorders
Amnesia
|
0.35%
1/289 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
Other adverse events
| Measure |
V212
n=289 participants at risk
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.
|
Placebo
n=62 participants at risk
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.
|
|---|---|---|
|
General disorders
Injection site erythema
|
46.0%
133/289 • Number of events 318 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
1.6%
1/62 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
General disorders
Injection site pain
|
42.2%
122/289 • Number of events 270 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
14.5%
9/62 • Number of events 11 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
General disorders
Injection site pruritus
|
8.3%
24/289 • Number of events 44 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
0.00%
0/62 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
General disorders
Injection site swelling
|
40.1%
116/289 • Number of events 255 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
4.8%
3/62 • Number of events 3 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
17/289 • Number of events 19 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
1.6%
1/62 • Number of events 1 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
|
Nervous system disorders
Headache
|
7.3%
21/289 • Number of events 30 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
3.2%
2/62 • Number of events 2 • Up to Day 140
All participants who received at least one dose of vaccine and had safety follow-up
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER