Concomitant Use of Hepatitis A Vaccine With Measles, Mumps, Rubella and Varicella Vaccine and Pneumococcal 7-Valent Conjugate Vaccine in Healthy 12-Month-Old Children (V251-067)

An Open, Randomized, Multicenter Study of the Safety, Tolerability, & Immunogenicity of VAQTA™ Given Concomitantly With PROQUAD™ and PREVNAR™ in Healthy Children 12 Months of Age

Hepatitis A vaccine will be given either alone or together with measles, mumps, rubella, and varicella vaccine and pneumococcal 7-valent conjugate vaccine at the first dose and together with measles, mumps, rubella, and varicella [Oka/Merck] virus vaccine at the second dose. Immunogenicity and safety data will be collected after each dose of vaccine.

Study Overview

• Status: Completed
• Conditions: Hepatitis A Virus
• Intervention / Treatment: Biological: Comparator: VAQTA™ (Hepatitis A vaccine); Biological: Comparator: ProQuad™ (Measles, Mumps, Rubella and Varicella vaccine); Biological: Comparator: Prevnar™ (Pneumococcal 7-Valent Conjugate vaccine)

Detailed Description

Vaccines: V251, Hepatitis A Vaccine, Inactivated (VAQTA™) administered with Measles, Mumps, Rubella and Varicella Vaccine (ProQuad™) and Pneumococcal 7-Valent Conjugate Vaccine (Prevnar™) will have a Duration of Treatment: 2 Doses, 6 months apart.

Vaccine: Hepatitis A Vaccine, Inactivated (VAQTA™), administered alone will have a Duration of Treatment: 2 Doses, 6 months apart.

• Study Type: Interventional
• Enrollment (Actual): 653
• Phase: Phase 4

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:

• 12- to 15-month-old males and females with no active liver disease
• A negative history of hepatitis A, measles, mumps, rubella, chickenpox, and/or zoster

Exclusion Criteria:

• Males and females previously vaccinated with hepatitis A, measles, mumps, rubella, and/or chickenpox vaccine
• Any immune deficiency
• History of allergy to any of the vaccine components
• History of any seizure disorder

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
Active Comparator: 1; Arm 1: VAQTA™ 0.5 mL injection (2 doses 6 months apart), ProQuad™ 0.5 mL injection (2 doses 6 months apart), Prevnar™ 0.5 mL injection (one dose), all vaccines administered concomitantly. 28 weeks of study duration.	Biological: Comparator: VAQTA™ (Hepatitis A vaccine); VAQTA™ 0.5 mL injection; Biological: Comparator: ProQuad™ (Measles, Mumps, Rubella and Varicella vaccine); ProQuad™ 0.5 mL injection; Biological: Comparator: Prevnar™ (Pneumococcal 7-Valent Conjugate vaccine); Prevnar™ 0.5 mL injection
Active Comparator: 2; Arm 2: ProQuad™ 0.5 mL injection (2 doses ~8 months apart), Prevnar™ 0.5 mL injection (one dose), both administered concomitantly, VAQTA™ 0.5 mL injection (2 doses 6 months apart) administered alone. 34 weeks of study duration.	Biological: Comparator: VAQTA™ (Hepatitis A vaccine); VAQTA™ 0.5 mL injection; Biological: Comparator: ProQuad™ (Measles, Mumps, Rubella and Varicella vaccine); ProQuad™ 0.5 mL injection; Biological: Comparator: Prevnar™ (Pneumococcal 7-Valent Conjugate vaccine); Prevnar™ 0.5 mL injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Response to Hepatitis A - Participants With a Serological Response	Number of participants with titer ≥10 mIU/mL, i.e., seropositive for hepatitis A antibody, regardless of initial serostatus	4 weeks Postdose 2 of hepatitis A vaccine (VAQTA™)
Antibody Response to Varicella - Participants With a Serological Response	Participants with varicella baseline antibody titer <1.25 gpELISA units/mL and Postdose 1 titers ≥1.25 gpELISA units/mL (seroconversion) and ≥5 gpELISA units/mL (seroprotection)	6 weeks Postdose 1 of varicella-containing vaccine (ProQuad™)
Antibody Response to Streptococcus Pneumoniae - Geometric Mean Titers	Serum antibodies to serotype-specific pneumococcal polysaccharides were determined by enzyme-linked immunosorbent assay	6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Participants With 1 or More Systemic Adverse Experience	Systemic adverse experiences are unfavorable or unintended changes in the body after getting study vaccine. They are collected the first 14 days after receipt of dose 1 of hepatitis A vaccine (VAQTA™) (Days 1 to 14) within the 6 week study period.	6 weeks post dose 1
Participants With 1 or More Systemic Adverse Experience	Systemic adverse experiences are unfavorable or unintended changes in the body after getting study vaccine. They are collected the first 14 days after receipt of dose 2 of hepatitis A vaccine (VAQTA™) (Days 1 to 14) within the 4 week study period.	4 weeks post dose 2
Participants With 1 or More Systemic Adverse Experience.	Systemic adverse experiences are unfavorable or unintended changes in the body after getting study vaccine. Collected the first 14 days after each of the 2 doses of hepatitis A vaccine (VAQTA™) (Days 1 to 14), given 6 months apart	6 months
Participants With 1 or More Injection-site Adverse Experience	Injection-site adverse experiences collected the first 5 days after receipt of dose 1 of hepatitis A vaccine (VAQTA™) (Days 1 to 5) within the 6 week study period.	6 weeks post dose 1
Participants With 1 or More Injection-site Adverse Experience	Injection-site adverse experiences collected the first 5 days after receipt of dose 2 of hepatitis A vaccine (VAQTA™) (Days 1 to 5) within the 4 week study period.	4 weeks post dose 2
Participants With 1 or More Injection-site Adverse Experience	Injection-site adverse experiences collected the first 5 days after receipt of each dose of hepatitis A vaccine (VAQTA™) (Days 1 to 5) over the 6 months in which the 2 doses of vaccine were administered.	6 months
Participants With Elevated Temperature (≥102.2F/ ≥39.0C)	Elevated temperatures measured the first 5 days after receipt of dose 1 of hepatitis A vaccine (VAQTA™) (Days 1 to 5) within the 6 week study period.	6 weeks post dose 1
Participants With Elevated Temperature (≥102.2F/ ≥39.0C)	Elevated temperatures measured the first 5 days after receipt of dose 2 of hepatitis A vaccine (VAQTA™) (Days 1 to 5) within the 4 week study period.	4 weeks post dose 2
Participants With Elevated Temperature (≥102.2F/ ≥39.0C)	Elevated temperatures measured the first 5 days after receipt of each dose of hepatitis A vaccine (VAQTA™) (Days 1 to 5) over the 6 months in which the 2 doses of vaccine were administered.	6 months
Participants With 1 or More Serious Vaccine-related Adverse Experience	Serious vaccine-related adverse experience causes death, persistent or significant disability, causes or prolong a hospital stay, is a cancer, an overdose, or life-threatening. They were collected during the entire study and believed due to study vaccine	6 weeks post dose 1
Participants With 1 or More Serious Vaccine-related Adverse Experience	Serious vaccine-related adverse experience causes death, persistent or significant disability, causes or prolong a hospital stay, is a cancer, an overdose, or life-threatening. They were collected during the entire study and believed due to study vaccine	4 weeks post dose 2
Participants With 1 or More Serious Vaccine-related Adverse Experience	Serious vaccine-related adverse experience causes death, persistent or significant disability, causes or prolong a hospital stay, is a cancer, an overdose, or life-threatening. They were collected during the entire study and believed due to study vaccine	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Response to Hepatitis A - Geometric Mean Titer	Geometric Mean Titer of hepatitis A antibody, regardless of initial serostatus	4 weeks Postdose 2 of hepatitis A vaccine (VAQTA™)
Antibody Response to Varicella - Geometric Mean Titer	Geometric Mean Titer of varicella antibody, baseline antibody titer was <1.25 gpELISA units/mL	6 weeks Postdose 1 of varicella-containing vaccine (ProQuad™)
Antibody Response to S. Pneumoniae Serotype 4 - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 4	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Antibody Response to S. Pneumoniae Serotype 6B - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 6B	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Antibody Response to S. Pneumoniae Serotype 9V - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 9V	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Antibody Response to S. Pneumoniae Serotype 14 - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 14	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Antibody Response to S. Pneumoniae Serotype 18C - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 18C	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Antibody Response to S. Pneumoniae Serotype 19F - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 19F	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Antibody Response to S. Pneumoniae Serotype 23F - Participants With a Serological Response	Number of participants with a postvaccination titer >=0.2 mcg/mL for S. pneumoniae serotype 23F	6 weeks postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Yetman RJ, Shepard JS, Duke A, Stek JE, Petrecz M, Klopfer SO, Kuter BJ, Schodel FP, Lee AW. Concomitant administration of hepatitis A vaccine with measles/mumps/rubella/varicella and pneumococcal vaccines in healthy 12- to 23-month-old children. Hum Vaccin Immunother. 2013 Aug;9(8):1691-7. doi: 10.4161/hv.24873. Epub 2013 Jun 6.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: April 7, 2006
• First Submitted That Met QC Criteria: April 7, 2006
• First Posted (Estimate): April 11, 2006

Study Record Updates

• Last Update Posted (Actual): April 13, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Hepatitis A Virus
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V251-067; 2005_075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No