A Study of the Safety and Tolerability of V419 in Healthy Infants at 2,4, 6 and 12 to 14 Months of Age (V419-003)

Safety, Tolerability, and Immunogenicity of 3 Different Formulations of a Liquid Hexavalent Combination Vaccine, HR5I When Administered to Healthy Hepatitis B Vaccine-Naive Infants at 2, 4, 6, and 12-14 Months of Age

The purpose of this study is to evaluate the safety, tolerability and immunogenicity of 3 formulations of the HR5I vaccine (Haemophilus influenzae type b conjugate, recombinant hepatitis B surface antigen, diphtheria, tetanus, 5-component acellular pertussis, and inactivated poliovirus Types 1, 2, and 3). The primary hypothesis is that at least 1 of the 3 formulations of HR5I administered as a primary series at 2, 4, and 6 months of age will be acceptable (similar to targeted rates) with respect to Postdose 3 antibody responses to all antigens.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections; Virus Diseases
• Intervention / Treatment: Biological: AR51 (12, 10); Biological: PR51 (3, 10); Biological: PR51 (6, 10); Biological: PENTACEL™; Biological: RECOMBIVAX HB™

Detailed Description

Participants will be randomized into 4 arms:

AR51 (12, 10): arm receiving vaccine formulation containing 12 mcg of polyribosylribitol phosphate (PRP) conjugated to tetanus toxoid (PRP-T) and 10 mcg of Hepatitis B surface antigen (HBsAg)

PR51 (3, 10): arm receiving vaccine formulation containing 3 mcg of polyribosylribitol phosphate conjugated to the outer membrane protein complex of Neisseria meningitides (PRP-OMPC) and 10 mcg of HBsAg

PR51 (6, 10): arm receiving vaccine formulation containing 6 mcg of PRP-OMPC and 10 mcg of HBsAg

PENTACEL™ + RECOMBIVAX HB™: open-label control group receiving PENTACEL™ (licensed vaccine for diphtheria, tetanus, pertussis, poliomyelitis, and invasive disease due to Haemophilus influenzae type b) and RECOMBIVAX HB™ (licensed vaccine for hepatitis)

• Study Type: Interventional
• Enrollment (Actual): 756
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infants 2 months of age who have not received prior vaccinations for Haemophilus influenzae type b (Hib), hepatitis B, Diptheria/Pertussis/Tetanus (DPT), or Polio

Exclusion Criteria:

• HIV infection in participant (child/mother)
• Documented HBsAg seropositivity in the participant (child or mother)
• History of invasive Hib disease, hepatitis B, diphtheria, tetanus, pertussis, or poliovirus infection
• History of seizure disorder
• Underlying medical conditions such as inborn errors of metabolism, failure to thrive, or any major congenital abnormalities requiring surgery
• Prior or anticipated receipt of immune globulin, blood, or blood products
• Known hypersensitivity to any component of the investigational or marketed vaccines being administered in this protocol
• Any history or condition that would exclude the participant from receiving any vaccine administered under this protocol based on the contraindications that appear in the package circulars for each component of these vaccines
• Any condition that, in the opinion of the investigator, is not stable or may interfere with the evaluation of the study objectives

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AR51 (12, 10); Participants were vaccinated with 0.5 ml of AR51 (12,10) formulation via intramuscular injection as a primary series at 2, 4, and 6 months of age, and as a booster at 12 to 14 months of age.	Biological: AR51 (12, 10); vaccine formulation containing 12 mcg of PRP-T and 10 mcg of HBsAg
Experimental: PR51 (3, 10); Participants were vaccinated with 0.5 ml of PR51 (3,10) formulation via intramuscular injection as a primary series at 2, 4, and 6 months of age, and as a booster at 12 to 14 months of age.	Biological: PR51 (3, 10); vaccine formulation containing 3 mcg of PRP-OMPC and 10 mcg of HBsAg
Experimental: PR51 (6, 10); Participants were vaccinated with 0.5 ml of PR51 (6,10) formulation via intramuscular injection as a primary series at 2, 4, and 6 months of age, and as a booster at 12 to 14 months of age.	Biological: PR51 (6, 10); vaccine formulation containing 6 mcg of PRP-OMPC and 10 mcg of HBsAg
Active Comparator: PENTACEL™ + RECOMBIVAX HB™; Participants were vaccinated with 0.5 ml each of PENTACEL™ + RECOMBIVAX HB™ via intramuscular injection as a primary series at 2, 4, and 6 months of age, and with 0.5 ml PENTACEL™ as a booster at 12 to 14 months of age.	Biological: PENTACEL™; licensed vaccine for diphtheria, tetanus, pertussis, poliomyelitis, and invasive disease due to Haemophilus influenzae type b, administered open-label; Biological: RECOMBIVAX HB™; licensed vaccine for hepatitis, administered open-label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with level of anti-PRP antibodies >1.0 μg/mL at the Postdose 3 time point	At 7 months of age (1 month after 3rd vaccination)
Percentage of participants with level of anti-HBsAg antibodies ≥10 mIU/L at the Postdose 3 time point	At 7 months of age (1 month after 3rd vaccination)
Percentage of participants with a ≥4-fold rise in levels of antibodies to pertussis antigens at the Postdose 3 time point	At 7 months of age (1 month after 3rd vaccination)
Percentage of participants with level of anti-diphtheria antibodies ≥0.01 IU/mL at the Postdose 3 time point	At 7 months of age (1 month after 3rd vaccination)
Percentage of participants with level of anti-tetanus antibodies ≥0.01 IU/mL at the Postdose 3 time point	At 7 months of age (1 month after 3rd vaccination)
Percentage of participants with neutralizing anti-poliovirus type antibodies at ≥1:8 dilution at the Postdose 3 time point	At 7 months of age (1 month after 3rd vaccination)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with level of anti-PRP antibodies >1.0 μg/mL at the Postdose 2 time point	At 6 months of age (2 months after 2nd vaccination)
Percentage of participants with level of anti-HBsAg antibodies ≥10 mIU/L at the Postdose 2 time point	At 6 months of age (2 months after 2nd vaccination)
Percentage of participants with a ≥4-fold rise in level of antibodies to pertussis antigens at the Postdose 2 time point	At 6 months of age (2 months after 2nd vaccination)
Percentage of participants with level of anti-diphtheria antibodies ≥0.01 IU/mL at the Postdose 2 time point	At 6 months of age (2 months after 2nd vaccination)
Percentage of participants with level of anti-tetanus antibodies ≥0.01 IU/mL at the Postdose 2 time point	At 6 months of age (2 months after 2nd vaccination)
Percentage of participants with neutralizing anti-poliovirus type antibodies at ≥1:8 dilution at the Postdose 2 time point	At 6 months of age (2 months after 2nd vaccination)
Number of participants with at least 1 adverse event (AE)	From 1st vaccination up to 14 days following last vaccination (up to 14.5 months)
Number of participants who discontinued study treatment due to an AE	From 1st vaccination up to 14 days following last vaccination (up to 14.5 months)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Diaz-Mitoma F, Halperin SA, Tapiero B, Hoffenbach A, Zappacosta PS, Radley D, Bradshaw S, Martin JC, Boslego JW, Hesley TM, Bhuyan PK, Silber JL. Safety and immunogenicity of three different formulations of a liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 4, 6 and 12-14 months of age. Vaccine. 2011 Feb 1;29(6):1324-31. doi: 10.1016/j.vaccine.2010.11.053. Epub 2010 Dec 4.

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): January 1, 2003
• Study Completion (Actual): January 1, 2003

Study Registration Dates

• First Submitted: October 29, 2007
• First Submitted That Met QC Criteria: October 29, 2007
• First Posted (Estimate): October 31, 2007

Study Record Updates

• Last Update Posted (Estimate): October 30, 2015
• Last Update Submitted That Met QC Criteria: October 29, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Virus Diseases; Bacterial Infections
• Other Study ID Numbers: V419-003; 2007_581 (Other Identifier: Merck Registration Number)