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)

Phase 2

Completed

• Conditions: Bacterial Infections; Virus Diseases
• Interventions: Biological: PR51 (6, 10); Biological: PENTACEL™; Biological: PR51 (3, 10); Biological: AR51 (12, 10); Biological: RECOMBIVAX HB™

• Registration Number: NCT00551915
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

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 Timeline

• Study Start: 2001-05
• Primary Completion: 2003-01
• Study Completion: 2003-01
• Study First Submitted: 2007-10-29
• Study First Submitted QC: 2007-10-29
• Study First Posted: 2007-10-31
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-29
• Last Update Posted: 2015-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 756

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PR51 (6, 10)	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.
PENTACEL™ + RECOMBIVAX HB™	PENTACEL™	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.
PR51 (3, 10)	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.
AR51 (12, 10)	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.
PENTACEL™ + RECOMBIVAX HB™	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)