Safety, Tolerability, and Immunogenicity of Measles, Mumps, Rubella, and Varicella (MMRV) Vaccine Made With an Alternative Manufacturing Process (AMP)(V221-027)

A Phase III Double-Blind, Randomized, Multicenter, Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Measles, Mumps, Rubella, Varicella (MMRV) Vaccine Made With an Alternative Manufacturing Process (AMP)

This study will compare the safety, tolerability, and immunogenicity of measles, mumps, rubella, and varicella (MMRV) vaccine made with an alternative manufacturing process with those of the 2006 process

Study Overview

• Status: Completed
• Conditions: Measles; Rubella; Mumps; Varicella
• Intervention / Treatment: Biological: MMRV (AMP); Biological: MMRV (2006 process)

• Study Type: Interventional
• Enrollment (Actual): 1412
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Negative clinical history for measles, mumps, rubella, varicella, and zoster

Exclusion Criteria:

• Received any measles, mumps, rubella, or varicella vaccine, either alone or in any combination at any time prior to the study, or is anticipated to receive any of these vaccines outside of study protocol, either alone or in any combination, during the study
• Received immune globulin, a blood transfusion or blood-derived products (does not include autologous blood/blood products) within 5 months (150 days) prior to any dose of the study vaccines or plans to receive these products while enrolled in this study
• Exposed to measles, mumps, rubella, varicella, or zoster within 4 weeks prior to the study vaccination
• Any congenital or acquired immune deficiency, neoplastic disease, or depressed immunity, including that resulting from steroid use or other immunosuppressive therapy
• Received 1) systemic immunomodulatory steroids [greater than the

equivalent of 2 mg/kg total daily dose of prednisone] within 3 months prior to

entering the study, or 2) any dose of systemic immunomodulatory steroids within

7 days prior to entering study, or 3) is expected to require systemic immunomodulatory steroids through the course of the study

• History of allergy or anaphylactoid reaction to gelatin, sorbitol, neomycin, egg proteins (eggs or egg products), chicken proteins, or any component of the study vaccines
• Received salicylates (eg, aspirin or aspirin-containing products) within 14 days prior to study vaccination
• Diagnosis of an active neurological disorder. Enrollment may be considered

when the disease process has been stabilized

• History of seizure disorder, including single febrile seizure
• Diagnosis of active untreated tuberculosis
• History of thrombocytopenia
• Born to a human immunodeficiency virus (HIV) infected mother

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMRV (AMP); Participants received two 0.5 mL subcutaneous injections of Mumps, Measles, Rubella, Varicella (MMRV) vaccine made with an alternative manufacturing process (AMP)	Biological: MMRV (AMP); Measles, mumps, rubella, and VZV vaccine made with an alternative manufacturing process. Participants will receive two 0.5 mL subcutaneous injections.
Active Comparator: MMRV (2006 process); Participants received two 0.5 mL subcutaneous injections of MMRV vaccine made with the 2006 manufacturing process	Biological: MMRV (2006 process); Measles, mumps, rubella, and VZV vaccine made with the 2006 manufacturing process. Participants will receive two 0.5 mL subcutaneous injections.; Other Names: ProQuad™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 gpELISA Units/mL	Sera were tested for VZV Immunoglobulin (IgG) antibody levels by a glycoprotein enzyme-linked immunosorbent assay (gpELISA)	Six weeks after vaccination 1
Percentage of Participants With Measles Virus Antibody Levels >=255 mIU/mL	Sera were tested for measles virus IgG antibody levels by an ELISA	Six weeks after vaccination 1
Percentage of Participants With Mumps Virus Antibody Levels >=10 Units/mL	Sera were tested for mumps virus IgG antibody levels by an enzyme-linked immunosorbent assay (ELISA)	Six weeks after vaccination 1
Percentage of Participants With Rubella Virus Antibody Levels >=10 International Units/mL (IU/mL)	Sera were tested for rubella virus IgG antibody levels by an ELISA	Six weeks after vaccination 1
Geometric Mean Titer (GMT) of VZV Antibodies	Sera were tested for VZV IgG antibody levels by gpELISA	Six weeks after vaccination 1
Geometric Mean Titer (GMT) of Measles Virus Antibodies	Sera were tested for measles virus IgG antibody levels by ELISA	Six weeks after vaccination 1
Geometric Mean Titer (GMT) of Mumps Virus Antibodies	Sera were tested for mumps virus IgG antibody levels by ELISA	Six weeks after vaccination 1
Geometric Mean Titer (GMT) of Rubella Virus Antibodies	Sera were tested for rubella virus IgG antibody levels by ELISA	Six weeks after vaccination 1
Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent)		Up to 5 days after vaccination 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Fever (>=102.2°F [39.0°C] or Oral Equivalent)		Up to 42 days after each vaccination
Percentage of Participants With Zoster-like Rash		Up to 42 days after each vaccination
Percentage of Participants With Mumps-like Symptoms		Up to 42 days after each vaccination
Percentage of Participants With Measles-like Rash		Up to 42 days after each vaccination
Percentage of Participants With Rubella-like Rash		Up to 42 days after each vaccination
Percentage of Participants With Varicella-like Rash		Up to 42 days after each vaccination
Percentage of Participants With an Injection-site Adverse Event	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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Injection-site AEs reported were solicited with a Vaccine Report Card.	Up to 5 days after each vaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Marshall GS, Senders SD, Shepard J, Twiggs JD, Gardner J, Hille D, Hartzel J, Valenzuela R, Stek JE, Helmond FA. A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process. Hum Vaccin Immunother. 2016 Aug 2;12(8):2188-2196. doi: 10.1080/21645515.2016.1165374. Epub 2016 May 5.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2012
• Primary Completion (Actual): July 2, 2013
• Study Completion (Actual): January 27, 2014

Study Registration Dates

• First Submitted: February 16, 2012
• First Submitted That Met QC Criteria: February 16, 2012
• First Posted (Estimate): February 22, 2012

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Stomatognathic Diseases; Mouth Diseases; DNA Virus Infections; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Salivary Gland Diseases; Togaviridae Infections; Rubivirus Infections; Rubulavirus Infections; Parotitis; Parotid Diseases; Measles; Herpes Zoster; Chickenpox; Rubella; Mumps
• Other Study ID Numbers: V221-027; P20930

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis