A Study to Test the Safety and Effectiveness of an Investigational Vaccine in Infants (V419-002)

Safety, Tolerability, and Immunogenicity of Four Different Formulations of a Liquid Hexavalent Combination Vaccine, HR5I (Haemophilus Influenzae Type b Conjugate, Recombinant Hepatitis B Surface Antigen, Diphtheria Toxoid, Tetanus Toxoid, 5-Component Acellular Pertussis Vaccine, and Inactivated Poliovirus Type 1, 2, and 3), When Administered to Healthy Hepatitis B Vaccine-Naïve Infants at 2, 3, 4, and 12 to 14 Months of Age

The purpose of this study is to evaluate the safety, tolerability and immunogenicity of 4 different 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 4 formulations of HR5I administered as a primary series at 2, 3, and 4 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: PR51 (6, 15)

Detailed Description

Participants will be randomized into 4 arms:

AR51 (12, 10): arm receiving vaccine formulation containing 12 mcg of polyribosylribitol phosphate (PRP) conjugates 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 PRP 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

PR51 (6, 15): arm receiving vaccine formulation containing 6 mcg of PRP-OMPC and 15 mcg of HBsAg

• Study Type: Interventional
• Enrollment (Actual): 708
• 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 :

• Documented HIV infection (child or mother)
• Documented HBsAg-seropositivity (child or mother)
• History of invasive Hib disease, hepatitis B, diphtheria, tetanus, pertussis, or poliovirus infection
• History of seizure disorder, developmental delay, or any other neurologic 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 vaccines being administered in this protocol
• Any history or condition that would exclude the child from receiving any vaccine administered under this protocol
• Any condition that, in the opinion of the investigator, 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, 3, and 4 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, 3, and 4 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, 3, and 4 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
Experimental: PR51 (6, 15); Participants were vaccinated with 0.5 ml of PR51 (6, 15) formulation via intramuscular injection as a primary series at 2, 3, and 4 months of age, and as a booster at 12 to 14 months of age.	Biological: PR51 (6, 15); vaccine formulation containing 6 mcg of PRP-OMPC and 15 mcg of HBsAg

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 5 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 5 months of age (1 month after 3rd vaccination)
Percentage of participants with a ≥4-fold rise in levels of antibodies to pertussis antigens (toxoid [PTxd], Filamentous Hemagglutinin [FHA], Fimbria 2 & Fimbria 3 [FIM], and Pertactin [PRN]) at the Postdose 3 time point	At 5 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 5 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 5 months of age (1 month after 3rd vaccination)
Percentage of participants with neutralizing anti-poliovirus antibodies (Types 1, 2, and 3) at ≥1:8 dilution at the Postdose 3 time point	At 5 months of age (1 month after 3rd vaccination)

Secondary Outcome Measures

Outcome Measure	Time Frame
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

• Halperin SA, Tapiero B, Diaz-Mitoma F, Law BJ, Hoffenbach A, Zappacosta PS, Radley D, McCarson BJ, Martin JC, Brackett LE, Boslego JW, Hesley TM, Bhuyan PK, Silber JL. Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age. Vaccine. 2009 Apr 28;27(19):2540-7. doi: 10.1016/j.vaccine.2008.11.115. Epub 2009 Jan 3.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 29, 2007
• First Submitted That Met QC Criteria: October 30, 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: V419-002; 2007_580 (Other Identifier: Merck Registration Number)