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

Primary Purpose

Varicella, Measles, Mumps

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ProQuad®
Infanrix® hexa
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Varicella focused on measuring Mumps and Rubella, Haemophilus influenzae type b (Infanrix® hexa)

Eligibility Criteria

12 Months - 23 Months (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

ProQuad® + Infanrix® hexa

ProQuad®

Infanrix® hexa

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

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).
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).
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.

Secondary Outcome Measures

Full Information

First Posted
February 5, 2007
Last Updated
February 19, 2018
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00432042
Brief Title
Immunogenicity and Safety Study of Proquad® and Infanrix® Hexa When Administered Concomitantly (V221-035)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
January 12, 2007 (Actual)
Primary Completion Date
March 27, 2008 (Actual)
Study Completion Date
March 27, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Varicella, Measles, Mumps, Rubella, Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, Haemophilus Infections
Keywords
Mumps and Rubella, Haemophilus influenzae type b (Infanrix® hexa)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
955 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ProQuad® + Infanrix® hexa
Arm Type
Experimental
Arm Description
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).
Arm Title
ProQuad®
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Infanrix® hexa
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
ProQuad®
Intervention Description
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]).
Intervention Type
Biological
Intervention Name(s)
Infanrix® hexa
Intervention Description
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).
Primary Outcome Measure Information:
Title
Percentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella
Description
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).
Time Frame
Day 42
Title
Percentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B
Description
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).
Time Frame
Day 42
Title
Post-vaccination Geometric Mean Titres (GMT) to Pertussis
Description
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.
Time Frame
Day 42

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
23 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Fiquet, MD
Organizational Affiliation
SPMSD
Official's Role
Study Director
Facility Information:
City
Alsfeld
Country
Germany
City
Bad Saulgau
Country
Germany
City
Bad Sobernheim
Country
Germany
City
Bad Säckingen
Country
Germany
City
Berlin
Country
Germany
City
Bielefeld
Country
Germany
City
Birkenfeld
Country
Germany
City
Bramsche
Country
Germany
City
Bretten
Country
Germany
City
Brunsbüttel
Country
Germany
City
Datteln
Country
Germany
City
Detmold
Country
Germany
City
Espelkamp
Country
Germany
City
Ettenheim
Country
Germany
City
Friedrichshafen
Country
Germany
City
Gerolstein
Country
Germany
City
Gifhorn
Country
Germany
City
Gütersloh
Country
Germany
City
Hamburg
Country
Germany
City
Heilbronn
Country
Germany
City
Herbolzheim
Country
Germany
City
Karlsruhe
Country
Germany
City
Kehl
Country
Germany
City
Koblenz
Country
Germany
City
Lauffen
Country
Germany
City
Mannheim
Country
Germany
City
Marbach
Country
Germany
City
Mönchengladbach
Country
Germany
City
München
Country
Germany
City
Neustadt A.d. Aisch
Country
Germany
City
Nidderau
Country
Germany
City
Oberhausen
Country
Germany
City
Oberkirch
Country
Germany
City
Offenburg
Country
Germany
City
Pegnitz
Country
Germany
City
Rodorf
Country
Germany
City
Schwieberdingen
Country
Germany
City
Schwäbisch Hall
Country
Germany
City
Traunreut
Country
Germany
City
Veitshöchheim
Country
Germany
City
Wanzleben
Country
Germany
City
Welzheim
Country
Germany
City
Wildeshausen
Country
Germany
City
Zwiesel
Country
Germany
City
Chiavari
Country
Italy
City
Ferrara
Country
Italy
City
Latisana
Country
Italy
City
Ragusa
Country
Italy
City
Sassari
Country
Italy
City
Taranto
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25765966
Citation
Deichmann KA, Ferrera G, Tran C, Thomas S, Eymin C, Baudin M. Immunogenicity and safety of a combined measles, mumps, rubella and varicella live vaccine (ProQuad (R)) administered concomitantly with a booster dose of a hexavalent vaccine in 12-23-month-old infants. Vaccine. 2015 May 11;33(20):2379-86. doi: 10.1016/j.vaccine.2015.02.070. Epub 2015 Mar 9.
Results Reference
derived

Learn more about this trial

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

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