Immunogenicity and Safety Study of Proquad® and Infanrix® Hexa When Administered Concomitantly (V221-035)

Study Overview
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Brief Summary
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Primary Objective: To demonstrate that ProQuad® can be administered concomitantly with a booster dose of Infanrix® hexa to healthy children 12 to 23 months of age without impairing either the antibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b; or to the 3 pertussis antibody titres measured at 42 days following vaccination. Secondary Objectives: To describe the antibody titres and the antibody response rates to measles, mumps, rubella, varicella, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b as measured at 42 days following vaccination by an Infanrix® hexa primary series schedule and all data are pooled. To evaluate the safety profile of ProQuad® when administered concomitantly with a booster dose of Infanrix® hexa by an Infanrix® hexa primary series schedule and all data are pooled.

Official Title
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An Open, Randomised, Comparative, Multicentre Study of the Immunogenicity and Safety of Concomitant Versus Separate Administration of a Combined Measles, Mumps, Rubella and Varicella Live Vaccine (ProQuad®) and a Booster Dose of Infanrix® Hexa in Healthy Children 12 to 23 Months of Age

Conditions
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Varicella, Measles, Mumps, Rubella, Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, Haemophilus Infections

Intervention / Treatment
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* Biological: ProQuad®
* Biological: Infanrix® hexa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants of either gender Aged 12 to 23 months No clinical history of measles, mumps, rubella, varicella and zoster For Italy: Primary vaccination with the combined diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine Infanrix® hexa as a 2-dose schedule, with receipt of the second dose ≥ 6 months prior to inclusion For Germany: Primary vaccination with the combined diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine Infanrix® hexa as a 3-dose schedule, with receipt of the third dose ≥ 6 months prior to inclusion Consent form signed by parent(s) according to local regulations or by the legal representative properly informed about the study Parent(s)/legal representative able to understand the protocol requirements and to fill in the Diary Card. Exclusion Criteria: Prior receipt of measles, mumps, rubella and/or varicella vaccine either alone or in any combination Any recent (<= 30 days) exposure to measles, mumps, rubella, varicella and/or zoster Receipt of any other diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and/or Haemophilus influenzae type b containing vaccine (either alone or in any combination) than Infanrix® hexa Any recent (<= 3 days) history of febrile illness Any severe chronic disease Active untreated tuberculosis Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition Any known blood dyscrasia, leukemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic or lymphatic systems Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection Prior known sensitivity/allergy to any component of the vaccines including neomycin, sorbitol or gelatin Any immune impairment or humoral/cellular deficiency, neoplastic disease or depressed immunity Any recent (<= 2 days) tuberculin test or scheduled tuberculin test through Visit 2 Any previous (<= 150 days) receipt of immune serum globulin or any blood-derived products or scheduled to be administered through Visit 2 Any recent (<= 30 days) receipt of an inactivated or a live non-study vaccine or scheduled non-study vaccination through Visit 2 Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives Any recent (≤30 days) participation or scheduled participation in any other clinical trial through Visit 2

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ProQuad® + Infanrix® hexa<br>Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42). | Biological: ProQuad®<br>* Participants received a 0.5 mL subcutaneous injection of ProQuad® containing the following live attenuated virus strains: measles virus Enders' Edmonston strain (≥3.00 log10 50% cell culture infectious dose [CCID]50), mumps virus Jeryl Lynn™ (Level B) strain (≥4.30 log10 CCID50), rubella virus Wistar RA 27/3 strain (≥3.00 log10 CCID50), and varicella virus Oka/Merck strain (≥3.99 log10 plaque-forming units [PFU]).<br>Biological: Infanrix® hexa<br>* Participants received a 0.5 mL intramuscular injection of Infanrix® hexa containing the following: diphtheria toxoid (≥30 IU), tetanus toxoid (≥40 IU), 3-component acellular pertussis (pertussis taxoid, filamentous haemagglutinin, and pertactin) (25 ug), Hepatitis B surface antigen recombinant (S protein) (10 ug), inactivated poliovirus types 1-3 (type 1: 40 D-antigen units; type 2: 8 D-antigen units; type 3: 32 D-antigen units), and Haemophilus influenzae type B (Hib) polysaccharide conjugate to tetanus toxoid (20-40 ug).<br>|
| Active Comparator: ProQuad®<br>Pediatric (12 to 23 months of age) participants received ProQuad® on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42). | Biological: ProQuad®<br>* Participants received a 0.5 mL subcutaneous injection of ProQuad® containing the following live attenuated virus strains: measles virus Enders' Edmonston strain (≥3.00 log10 50% cell culture infectious dose [CCID]50), mumps virus Jeryl Lynn™ (Level B) strain (≥4.30 log10 CCID50), rubella virus Wistar RA 27/3 strain (≥3.00 log10 CCID50), and varicella virus Oka/Merck strain (≥3.99 log10 plaque-forming units [PFU]).<br>|
| Active Comparator: Infanrix® hexa<br>Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42). | Biological: Infanrix® hexa<br>* Participants received a 0.5 mL intramuscular injection of Infanrix® hexa containing the following: diphtheria toxoid (≥30 IU), tetanus toxoid (≥40 IU), 3-component acellular pertussis (pertussis taxoid, filamentous haemagglutinin, and pertactin) (25 ug), Hepatitis B surface antigen recombinant (S protein) (10 ug), inactivated poliovirus types 1-3 (type 1: 40 D-antigen units; type 2: 8 D-antigen units; type 3: 32 D-antigen units), and Haemophilus influenzae type B (Hib) polysaccharide conjugate to tetanus toxoid (20-40 ug).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella | The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 2: ProQuad® was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre <255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre <10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre <10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre <1.25 gpELISA units/mL. Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA). | Day 42 | 
| Percentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B | The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: Hepatitis B antibody titre ≥10 IU/mL and Haemophilus Influenzae Type b antibody titre ≥1 ug/mL. Hepatitis B antibody levels were determined using anti-HBs ORTHO ECi Immunodiagnostic Assay. Haemophilus Influenzae Type b antibody (anti-polyribosylribitol phosphate [PRP]) levels were determined with radioimmunoassay (RIA) or with enzyme immunoassay (EIA). | Day 42 | 
| Post-vaccination Geometric Mean Titres (GMT) to Pertussis | The GMT to pertussis were compared in Arm1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa. Anti-pertussis toxin (anti-PT), anti-filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) were determined using ELISA on solid phase based on sandwich principle. | Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mumps and Rubella, Haemophilus influenzae type b (Infanrix® hexa)