Immunogenicity and Safety Study of ZOSTAVAX Administered by Intramuscular or Subcutaneous Route to Participants Aged From 50 Years Old (V211-045)
Primary Purpose
Herpes Zoster
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ZOSTAVAX
Sponsored by
About this trial
This is an interventional prevention trial for Herpes Zoster
Eligibility Criteria
Inclusion Criteria:
- Adults aged >=50 years
- Varicella history-positive or residence for >30 years in a country with endemic VZV infection
Exclusion Criteria:
- Febrile illness
- History of hypersensitivity or anaphylactoid reaction to any of the vaccine components
- Prior herpes zoster episode clinically diagnosed or exposure to varicella or herpes zoster within the 4 weeks prior to vaccination
- Prior receipt of varicella or zoster vaccine
- Active untreated tuberculosis
- Thrombocytopenia, any other coagulation disorder contraindicating intramuscular injection
- Receipt of medication / vaccine that may interfere with study assessments
- Known or suspected immune dysfunction
- User of recreational / illicit drugs or subject with alcohol abuse or dependence within the last year
- Any condition that might interfere with the interpretation of the study,
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ZOSTAVAX intramuscular (IM) route
ZOSTAVAX subcutaneous (SC) route
Arm Description
Single dose of 0.65 mL via IM injection
Single dose of 0.65 mL via SC injection
Outcomes
Primary Outcome Measures
Geometric Mean Titre (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks Post-vaccination
Blood samples taken at 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA).
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: IM Route
Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination
Secondary Outcome Measures
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: SC Route
Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-vaccination/GMT Pre-vaccination
Geometric Mean Count (GMCs) of VZV Interferon Gamma ((IFN-γ) Enzyme-Linked ImmunoSpot (ELISPOT) Antibodies
Blood samples taken 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMC's. Results were reported as ELISPOT count/10^6 Peripheral Blood Mononuclear Cells (PBMC)
Geometric Mean Fold Rise (GMFR) of IFN-γ ELISPOT Antibodies
Blood samples taken pre-vaccination and 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMFR.
Percentage of Participants Who Report at Least 1 Injection-site Adverse Reaction
Participants entered data into daily diary card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain for 1st 4 days post-vaccination. Additionally, injection site reactions not prompted on diary card (unsolicited) were collected up 28 days post-vaccination. All injection site reactions (solicited or unsolicited) were recorded.
Percentage of Participants Who Report at Least 1 Systemic Adverse Event
An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) were summarized. These events included rashes of interest: i.e. Varicella, Varicella-like rashes, Herpes zoster or shingles and Herpes zoster-like rashes and other systemic adverse events.
Percentage of Participants Who Report at Least 1 Serious Adverse Event
A serious adverse event (SAE) is 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. The percentage of participants who reported an SAE within 35 days of vaccination were recorded.
Full Information
NCT ID
NCT01391546
First Posted
July 7, 2011
Last Updated
December 20, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01391546
Brief Title
Immunogenicity and Safety Study of ZOSTAVAX Administered by Intramuscular or Subcutaneous Route to Participants Aged From 50 Years Old (V211-045)
Official Title
An Open-label, Randomised, Comparative, Multicentre Study of the Immunogenicity and Safety of ZOSTAVAX When Administered by Intramuscular Route or Subcutaneous Route to Subjects of 50 Years of Age and Older
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
June 20, 2011 (Actual)
Primary Completion Date
October 15, 2012 (Actual)
Study Completion Date
October 15, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
PRIMARY OBJECTIVES
Two co-primary objectives are:
To demonstrate that the immunogenicity of ZOSTAVAX administered by intramuscular route (IM) is non-inferior to ZOSTAVAX administered by subcutaneous route (SC)
To demonstrate that ZOSTAVAX administered by IM route induces an acceptable fold-rise of varicella zoster virus (VZV) antibody titre from pre to 4-week post-vaccination
SECONDARY OBJECTIVES
Immunogenicity objectives
To evaluate the immunogenicity as measured by VZV antibody titre at 4 weeks following ZOSTAVAX administered by IM or SC route
To evaluate the immune response as measured by a second assay, the VZV Interferon gamma Enzyme-linked immunospot (ELISPOT) at 4 weeks following ZOSTAVAX administered by IM or SC route
Safety objective
- To describe the safety profile of ZOSTAVAX administered by IM or SC route
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Herpes Zoster
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
354 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ZOSTAVAX intramuscular (IM) route
Arm Type
Experimental
Arm Description
Single dose of 0.65 mL via IM injection
Arm Title
ZOSTAVAX subcutaneous (SC) route
Arm Type
Active Comparator
Arm Description
Single dose of 0.65 mL via SC injection
Intervention Type
Biological
Intervention Name(s)
ZOSTAVAX
Other Intervention Name(s)
V211
Intervention Description
1 dose 0.65 mL
Primary Outcome Measure Information:
Title
Geometric Mean Titre (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks Post-vaccination
Description
Blood samples taken at 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA).
Time Frame
4 week post-vaccination
Title
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: IM Route
Description
Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination
Time Frame
Pre-vaccination (Day 0) and 4 week post-vaccination
Secondary Outcome Measure Information:
Title
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: SC Route
Description
Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-vaccination/GMT Pre-vaccination
Time Frame
Pre-vaccination (Day 0) and 4 week post-vaccination
Title
Geometric Mean Count (GMCs) of VZV Interferon Gamma ((IFN-γ) Enzyme-Linked ImmunoSpot (ELISPOT) Antibodies
Description
Blood samples taken 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMC's. Results were reported as ELISPOT count/10^6 Peripheral Blood Mononuclear Cells (PBMC)
Time Frame
4 week post-vaccination
Title
Geometric Mean Fold Rise (GMFR) of IFN-γ ELISPOT Antibodies
Description
Blood samples taken pre-vaccination and 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMFR.
Time Frame
Pre-vaccination (Day 0) and 4 week post-vaccination
Title
Percentage of Participants Who Report at Least 1 Injection-site Adverse Reaction
Description
Participants entered data into daily diary card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain for 1st 4 days post-vaccination. Additionally, injection site reactions not prompted on diary card (unsolicited) were collected up 28 days post-vaccination. All injection site reactions (solicited or unsolicited) were recorded.
Time Frame
up to 28 days after vaccination
Title
Percentage of Participants Who Report at Least 1 Systemic Adverse Event
Description
An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) were summarized. These events included rashes of interest: i.e. Varicella, Varicella-like rashes, Herpes zoster or shingles and Herpes zoster-like rashes and other systemic adverse events.
Time Frame
up to Day 28 after vaccination
Title
Percentage of Participants Who Report at Least 1 Serious Adverse Event
Description
A serious adverse event (SAE) is 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. The percentage of participants who reported an SAE within 35 days of vaccination were recorded.
Time Frame
up to 35 days after vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Adults aged >=50 years
Varicella history-positive or residence for >30 years in a country with endemic VZV infection
Exclusion Criteria:
Febrile illness
History of hypersensitivity or anaphylactoid reaction to any of the vaccine components
Prior herpes zoster episode clinically diagnosed or exposure to varicella or herpes zoster within the 4 weeks prior to vaccination
Prior receipt of varicella or zoster vaccine
Active untreated tuberculosis
Thrombocytopenia, any other coagulation disorder contraindicating intramuscular injection
Receipt of medication / vaccine that may interfere with study assessments
Known or suspected immune dysfunction
User of recreational / illicit drugs or subject with alcohol abuse or dependence within the last year
Any condition that might interfere with the interpretation of the study,
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
25555381
Citation
Diez-Domingo J, Weinke T, Garcia de Lomas J, Meyer CU, Bertrand I, Eymin C, Thomas S, Sadorge C. Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged >/=50 years: a randomised non-inferiority clinical trial. Vaccine. 2015 Feb 4;33(6):789-95. doi: 10.1016/j.vaccine.2014.12.024. Epub 2014 Dec 30.
Results Reference
result
Learn more about this trial
Immunogenicity and Safety Study of ZOSTAVAX Administered by Intramuscular or Subcutaneous Route to Participants Aged From 50 Years Old (V211-045)
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