Clinical trial NCT00551629: A Study to Test the Safety and Effectiveness of an Investigational Vaccine in Infants (V419-002)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bacterial Infections; Virus Diseases
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-10-31
Enrollment: 708
Sex: ALL
Minimum age (years): 6
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants with level of anti-PRP antibodies >1.0 μg/mL at the Postdose 3 time point
timeFrame: At 5 months of age (1 month after 3rd vaccination)
measure: Percentage of participants with level of anti-HBsAg antibodies ≥10 mIU/L at the Postdose 3 time point
timeFrame: At 5 months of age (1 month after 3rd vaccination)
measure: 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
timeFrame: At 5 months of age (1 month after 3rd vaccination)
measure: Percentage of participants with level of anti-diphtheria antibodies ≥0.01 IU/mL at the Postdose 3 time point
timeFrame: At 5 months of age (1 month after 3rd vaccination)
measure: Percentage of participants with level of anti-tetanus antibodies ≥0.01 IU/mL at the Postdose 3 time point
timeFrame: At 5 months of age (1 month after 3rd vaccination)
measure: Percentage of participants with neutralizing anti-poliovirus antibodies (Types 1, 2, and 3) at ≥1:8 dilution at the Postdose 3 time point
timeFrame: At 5 months of age (1 month after 3rd vaccination)
Secondary outcomes:
measure: Number of participants with at least 1 adverse event (AE)
timeFrame: From 1st vaccination up to 14 days following last vaccination (up to 14.5 months)
measure: Number of participants who discontinued study treatment due to an AE
timeFrame: From 1st vaccination up to 14 days following last vaccination (up to 14.5 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.