Concomitant Use of Hepatitis A Vaccine, Inactivated With Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) and Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Given to Healthy Children 15 Months of Age (V251-068)

An Open, Randomized, Multicenter Study of the Safety, Tolerability, and Immunogenicity of VAQTA™ Given Concomitantly With PedvaxHIB™ and Infanrix™ in Healthy Children 15 Months of Age

This two-stage study evaluates the immunogenicity, safety, and tolerability of the administration of VAQTA™ (Hepatitis A Vaccine, Inactivated) concomitantly with PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]) and Infanrix™ (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, GlaxoSmithKline) versus the administration of VAQTA™ in healthy children 15 months of age at study entry.

Study Overview

• Status: Completed
• Conditions: Hepatitis A Virus
• Intervention / Treatment: Biological: Comparator: VAQTA™; Biological: Comparator: Infanrix™; Biological: Comparator: PedvaxHIB™

Detailed Description

In stage I, VAQTA™ given concomitantly with Infanrix™ and/or PedvaxHIB™ was evaluated.

In stage 2: Two (2) doses of the VAQTA™ vaccine were administered at least 6 months apart. Safety data was collected after each dose.

• Study Type: Interventional
• Enrollment (Actual): 1274
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage 1) Healthy males and females 15 months of age with no active liver disease and a negative history of hepatitis A who have been vaccinated against Haemophilus influenzae type b (Hib), diphtheria, tetanus, and pertussis diseases
• Stage 2) Healthy males and females 12 to 17 months of age with no active liver disease and a negative history of hepatitis A

Exclusion Criteria:

• Stage 1) Males and females previously vaccinated with hepatitis A vaccine, any immune deficiency, a history of allergy to any of the vaccine components, a history of seizure disorder or a neurologic disorder that would contraindicate pertussis vaccine, or a bleeding disorder
• Stage 2) Males and females previously vaccinated with hepatitis A vaccine, any immune deficiency, a history of allergy to any of the vaccine components, or a history of bleeding 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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VAQTA™, PedvaxHIB™ and Infanrix™/VAQTA™ (Stage 1); Day 1: VAQTA™ (first dose), PedvaxHIB™ and Infanrix™ were administered concomitantly at different injection sites. Week 24: The second dose of VAQTA™ was administered.	Biological: Comparator: VAQTA™; VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.; Biological: Comparator: Infanrix™; Infanrix™ (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, GlaxoSmithKline). One intramuscular 0.5-mL injection of Infanrix™ was administered at the first study visit.; Biological: Comparator: PedvaxHIB™; PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.; Other Names: One intramuscular 0.5-mL injection of PedvaxHIB™ was administered to all subjects at the first study; visit in all treatment groups in the study.
Experimental: PedvaxHIB™ and Infanrix™/VAQTA™/VAQTA™ (Stage 1); Day 1: PedvaxHIB™ and Infanrix™ were administered concomitantly at different injection sites. Week 4: The first dose of VAQTA™ was administered. Week 28: The second dose of VAQTA™ was administered.	Biological: Comparator: VAQTA™; VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.; Biological: Comparator: Infanrix™; Infanrix™ (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, GlaxoSmithKline). One intramuscular 0.5-mL injection of Infanrix™ was administered at the first study visit.; Biological: Comparator: PedvaxHIB™; PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.; Other Names: One intramuscular 0.5-mL injection of PedvaxHIB™ was administered to all subjects at the first study; visit in all treatment groups in the study.
Experimental: VAQTA™, PedvaxHIB™/VAQTA™ (Stage 1); Day 1: VAQTA™ (first dose) and PedvaxHIB™ were administered concomitantly at different injection sites. Week 24: The second dose of VAQTA™ was administered.	Biological: Comparator: VAQTA™; VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.; Biological: Comparator: PedvaxHIB™; PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.; Other Names: One intramuscular 0.5-mL injection of PedvaxHIB™ was administered to all subjects at the first study; visit in all treatment groups in the study.
Experimental: PedvaxHIB™/VAQTA™/VAQTA™ (Stage 1); Day 1: PedvaxHIB™ was administered. Week 4: The first dose of VAQTA™ was administered. Week 28: The second dose of VAQTA™ was administered.	Biological: Comparator: VAQTA™; VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.; Biological: Comparator: PedvaxHIB™; PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.; Other Names: One intramuscular 0.5-mL injection of PedvaxHIB™ was administered to all subjects at the first study; visit in all treatment groups in the study.
Experimental: VAQTA™/VAQTA™ (Stage 2); Day 1: The first dose of VAQTA™ was administered. Week 24: The second dose of VAQTA™ was administered.	Biological: Comparator: VAQTA™; VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seropositivity Rate (SPR) to Hepatitis A	SPR is the percent of participants with Hepatitis A antibody titers >= 10 milli-International Units/milliliter (mIU/mL), 4 weeks after dose 2 of VAQTA™ regardless of their initial serostatus. Antibody titers to Hepatitis A virus (HAV) were detected in participants' serum samples using an Enzyme Immunoassay (EIA).	4 weeks after dose 2 of VAQTA™
Antibody Response Rate to Haemophilus Influenzae Type b (Hib)	Antibodies to the Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) are assessed in participants serum using radioimmunoassay (RIA). The limit of detection (LOD) for the RIA is 6.60 ng/mL. The antibody response rate is defined as the percentage of participants with anti-PRP titers >1.0 mcg/mL, 4 weeks postvaccination with PedvaxHIB™.	4 weeks postvaccination with PedvaxHIB™
Number of Participants With Adverse Events (AE)	Systemic and injection site AEs were collected from participants receiving; VAQTA™ concomitantly with Infanrix™ and PedvaxHIB™ or PedvaxHIB™ (Stage I); VAQTA™ non-concomitantly with Infanrix™ and PedvaxHIB™ or PedvaxHIB™ (Stage I); VAQTA™ administered alone (Stage II) Safety data was collected on a standardized Vaccination Report Card (VRC) following each dose. Participants returned the VRC after the safety follow-up period for each dose of VAQTA™. AEs determined by the investigator to be possibly, probably or definitely related to the vaccine are reported as Vaccine-related AE.	Days 1 to 14 after any dose of VAQTA™ for systemic AEs, and Days 1 to 5 after any dose of VAQTA™ for injection-site AEs
Geometric Mean Titers (GMTs) to Antibodies for the Pertussis Toxin (PT), Pertussis Filamentous Hemagglutinin Antibody (FHA), and Pertactin (PRN) Components of Infanrix™	GMTs for antibodies to PT, FHA, and PRN were measured in serum samples of participants vaccinated with Infanrix™. IgG antibodies to PT were assessed using the anti-pertussis toxin enzyme-linked immunosorbent assay (anti-PT ELISA), with the LOD of 2.4 ELU/mL. IgG antibodies to FHA were assessed using the anti-pertussis filamentous hemagglutinin enzyme-linked immunosorbent assay (anti-FHA ELISA), with the LOD of 2.0 ELU/mL. IgG antibodies to PRN were assessed using the anti-pertussis pertactin enzyme-linked immunosorbent assay (anti-PRN ELISA), with the LOD of 3.3 ELU/mL.	4 weeks postvaccination with Infanrix™

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Petrecz M, Ramsey KP, Stek JE, Martin JC, Klopfer SO, Kuter B, Schodel FP, Lee AW. Concomitant use of VAQTA with PedvaxHIB and Infanrix in 12 to 17 month old children. Hum Vaccin Immunother. 2016;12(2):503-11. doi: 10.1080/21645515.2015.1080395.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: February 8, 2006
• First Submitted That Met QC Criteria: February 8, 2006
• First Posted (Estimate): February 10, 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
• Other Study ID Numbers: V251-068; 2005_076

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