Immunogenicity and Safety Study of ZOSTAVAX Administered by Intramuscular or Subcutaneous Route to Participants Aged From 50 Years Old (V211-045)

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

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

Study Overview

• Status: Completed
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: ZOSTAVAX

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZOSTAVAX intramuscular (IM) route; Single dose of 0.65 mL via IM injection	Biological: ZOSTAVAX; 1 dose 0.65 mL; Other Names: V211
Active Comparator: ZOSTAVAX subcutaneous (SC) route; Single dose of 0.65 mL via SC injection	Biological: ZOSTAVAX; 1 dose 0.65 mL; Other Names: V211

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	4 week post-vaccination
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	Pre-vaccination (Day 0) and 4 week post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Pre-vaccination (Day 0) and 4 week post-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)	4 week post-vaccination
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.	Pre-vaccination (Day 0) and 4 week post-vaccination
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.	up to 28 days after vaccination
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.	up to Day 28 after vaccination
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.	up to 35 days after vaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2011
• Primary Completion (Actual): October 15, 2012
• Study Completion (Actual): October 15, 2012

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 8, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster
• Other Study ID Numbers: V211-045 (Other Identifier: Merck Protocol Number); ZTV03C (Other Identifier: MCMVaccBV (SPMSD) Protocol Number); 2009-012458-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• 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