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Safety and Immunogenicity of Zoster Vaccine (ZOSTAVAX™) Made With an Alternative Manufacturing Process (AMP) (V211-042 AM1)

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ClinicalTrials.gov Identifier: NCT01505647
Recruitment Status : Completed
First Posted : January 6, 2012
Results First Posted : July 3, 2013
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Herpes Zoster
Shingles
Interventions Biological: Zoster Vaccine, Live (AMP)
Biological: Zoster Vaccine, Live
Enrollment 498
Recruitment Details  
Pre-assignment Details One participant in the ZOSTAVAX™ (AMP) group was randomized but not vaccinated, making the number of participants vaccinated in this group 331
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description Zoster Vaccine, Live Alternative Manufacturing Process (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1 Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
Period Title: Day 1 Through Day 42 Follow-up
Started 332 166
Vaccinated 331 166
Completed 329 166
Not Completed 3 0
Reason Not Completed
Lost to Follow-up             1             0
Physician Decision             1             0
Withdrawal by Subject             1             0
Period Title: Day 43 Through Day 182 Follow-up
Started 329 166
Completed 328 163
Not Completed 1 3
Reason Not Completed
Death             0             1
Lost to Follow-up             1             2
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™ Total
Hide Arm/Group Description Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1 Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1 Total of all reporting groups
Overall Number of Baseline Participants 332 166 498
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 332 participants 166 participants 498 participants
62.9  (7.1) 62.4  (7.0) 62.8  (7.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 166 participants 498 participants
Female
196
  59.0%
99
  59.6%
295
  59.2%
Male
136
  41.0%
67
  40.4%
203
  40.8%
1.Primary Outcome
Title Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody
Hide Description VZV antibody titers were determined by glycoprotein enzyme-linked immunosorbent assay (gpELISA)
Time Frame Day 1 and Week 6 postvaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis included all vaccinated participants except those who had protocol deviations that interfered with the assessment of antibody response, developed suspected varicella or herpes zoster rashes before blood sampling, or reported an exposure to varicella or herpes zoster
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description:
Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1
Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
Overall Number of Participants Analyzed 330 166
Geometric Mean (95% Confidence Interval)
Unit of Measure: Units/mL
Day 1 postvaccination; n = 330, 166
235.7
(211.7 to 262.5)
208.2
(176.4 to 245.7)
Week 6 postvaccination; n = 320, 164
532.6
(489.2 to 579.9)
457.1
(403.3 to 518.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ZOSTAVAX™ (AMP), ZOSTAVAX™
Comments The hypothesis tested is that the GMT at Week 6 postvaccination with ZOSTAVAX™ (AMP) vaccine is non-inferior to that with the current process vaccine
Type of Statistical Test Non-Inferiority or Equivalence
Comments The GMT induced by ZOSTAVAX™ (AMP) vaccine is statistically non-inferior to that induced by the current process vaccine if the lower bound of the 95% confidence interval of the GMT ratio is >0.67.
Statistical Test of Hypothesis P-Value <0.001
Comments The threshold for statistical significance is 0.025 (1-sided). The P-value was not adjusted.
Method Longitudinal regression model
Comments The analyzed GMT ratio, 95% confidence interval, and P-value were based on a longitudinal regression model adjusting for age and vaccination group
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.98 to 1.20
Estimation Comments [Not Specified]
2.Primary Outcome
Title Geometric Mean Fold Rise (GMFR) in VZV Antibody Titers
Hide Description VZV antibody titers were determined by gpELISA. The GMFR reports the geometric mean of the ratio of individual participant VZV antibody titers at Week 6 / Day 1 (Baseline).
Time Frame Day 1 (Baseline) to Week 6 postvaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis included all vaccinated participants except those who had protocol deviations that interfered with the assessment of antibody response, developed suspected varicella or herpes zoster rashes before blood sampling, or reported an exposure to varicella or herpes zoster.
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description:
Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1
Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
Overall Number of Participants Analyzed 320 164
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
2.3
(2.1 to 2.4)
2.2
(2.0 to 2.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ZOSTAVAX™ (AMP)
Comments The hypothesis tested was that ZOSTAVAX™ (AMP) induces an acceptable GMFR in VZV antibody titer from prevaccination to 6 weeks postvaccination
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The threshold for statistical significance is 0.025 (1-sided). The P-value was not adjusted.
Method t-test, 1 sided
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With One or More Adverse Experiences (AEs)
Hide Description

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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse experience.

Time Frame Day 1 to Day 42 postvaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis included all vaccinated participants with safety follow-up data. One participant in the AMP vaccine group was vaccinated but lost to follow-up without safety follow-up.
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description:
Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1
Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
Overall Number of Participants Analyzed 330 166
Measure Type: Number
Unit of Measure: Participants
205 99
4.Secondary Outcome
Title Number of Participants With One or More Serious Adverse Experience (SAE) Day 1 to 42 Postvaccination
Hide Description An SAE is defined as any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an "other important medical event" based on medical judgement
Time Frame Day 1 to Day 42 postvaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis included all vaccinated participants with safety follow-up data. One participant in the AMP vaccine group was vaccinated but lost to follow-up without safety follow-up.
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description:
Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1
Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
Overall Number of Participants Analyzed 330 166
Measure Type: Number
Unit of Measure: Participants
1 2
5.Secondary Outcome
Title Number of Participants With One or More Serious Adverse Experience Day 1 to 182 Postvaccination
Hide Description An SAE is defined as any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an "other important medical event" based on medical judgement
Time Frame Day 1 to Day 182 postvaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis included all vaccinated participants with safety follow-up data. One participant in the AMP vaccine group was vaccinated but lost to follow-up without safety follow-up.
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description:
Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1
Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
Overall Number of Participants Analyzed 330 166
Measure Type: Number
Unit of Measure: Participants
4 8
Time Frame Serious Adverse Events: Day 1 to Day 182 postvaccination; Other Adverse Events: Day 1 to Day 42 postvaccination
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ZOSTAVAX™ (AMP) ZOSTAVAX™
Hide Arm/Group Description Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1 Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1
All-Cause Mortality
ZOSTAVAX™ (AMP) ZOSTAVAX™
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
ZOSTAVAX™ (AMP) ZOSTAVAX™
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/330 (1.21%)      8/166 (4.82%)    
Cardiac disorders     
Cardiac failure congestive  0/330 (0.00%)  0 1/166 (0.60%)  1
Ear and labyrinth disorders     
Vertigo  0/330 (0.00%)  0 1/166 (0.60%)  1
Gastrointestinal disorders     
Acquired oesophageal web  1/330 (0.30%)  1 0/166 (0.00%)  0
Gastrointestinal haemorrhage  0/330 (0.00%)  0 1/166 (0.60%)  1
Ileus paralytic  0/330 (0.00%)  0 1/166 (0.60%)  1
Hepatobiliary disorders     
Bile duct stone  0/330 (0.00%)  0 1/166 (0.60%)  1
Cholangitis  0/330 (0.00%)  0 1/166 (0.60%)  1
Gallbladder perforation  0/330 (0.00%)  0 1/166 (0.60%)  1
Infections and infestations     
Enterocolitis infectious  0/330 (0.00%)  0 1/166 (0.60%)  1
Gastroenteritis salmonella  1/330 (0.30%)  1 0/166 (0.00%)  0
Injury, poisoning and procedural complications     
Traumatic liver injury  0/330 (0.00%)  0 1/166 (0.60%)  1
Concussion  0/330 (0.00%)  0 1/166 (0.60%)  1
Musculoskeletal and connective tissue disorders     
Muscle spasms  1/330 (0.30%)  1 0/166 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  0/330 (0.00%)  0 1/166 (0.60%)  1
Psychiatric disorders     
Psychotic disorder  1/330 (0.30%)  1 0/166 (0.00%)  0
Depression  0/330 (0.00%)  0 1/166 (0.60%)  1
Respiratory, thoracic and mediastinal disorders     
Chylothorax  0/330 (0.00%)  0 1/166 (0.60%)  1
Pleural effusion  1/330 (0.30%)  1 0/166 (0.00%)  0
1
Term from vocabulary, MedDRA (15.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ZOSTAVAX™ (AMP) ZOSTAVAX™
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   186/330 (56.36%)      85/166 (51.20%)    
General disorders     
Injection-site erythema  135/330 (40.91%)  138 66/166 (39.76%)  68
Injection-site pain  146/330 (44.24%)  153 68/166 (40.96%)  69
Injection-site pruritus  22/330 (6.67%)  23 13/166 (7.83%)  15
Injection-site swelling  106/330 (32.12%)  107 53/166 (31.93%)  56
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01505647    
Other Study ID Numbers: V211-042
First Submitted: January 4, 2012
First Posted: January 6, 2012
Results First Submitted: April 10, 2013
Results First Posted: July 3, 2013
Last Update Posted: April 12, 2017