Clinical trial NCT00566527: Comparative Study of Immunogenicity and Safety of a 2-dose Regimen of ProQuad® Manufactured With rHA (V221-038)
Official title: An Open-label, Randomised, Comparative, Multi-centre Study of the Immunogenicity and Safety of a 2-dose Regimen of ProQuad® Manufactured With rHA Administered to Healthy Children From 9 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Measles
Mumps
Rubella
Varicella
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-12-03
Enrollment: 1620
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary study objectives are:

* To demonstrate that a 2-dose regimen of ProQuad® manufactured with recombinant Human Albumin (rHA) administered at a 3-month interval to healthy children of 11 months of age at the time of Dose 1 is as immunogenic as in healthy children of 12 months of age at the time of Dose 1.
* To demonstrate that a 2-dose regimen of ProQuad® rHA administered at a 3-month interval to healthy children of 9 months of age at the time of Dose 1 is as immunogenic as in healthy children of 12 months of age at the time of Dose 1.
* To demonstrate that a 2-dose regimen of ProQuad® rHA administered at a 3-month interval to healthy children of 11 months of age and 9 months of age at the time of Dose 1 is well-tolerated compared to children of 12 months of age at the time of Dose 1.

The first primary hypothesis was that a 2-dose regimen of ProQuad® rHA, administered at a 3-month interval to children of 11 months of age, would be non-inferior in terms of antibody response rates to measles, mumps, rubella, and varicella at Day 42 following Dose 2, to the same regimen in children of 12 months of age at the time of Dose 1.

If the first primary hypothesis was demonstrated, the second primary hypothesis was that a 2-dose regimen of ProQuad® rHA, administered at a 3-month interval to children of 9 months of age, would be non-inferior in terms of antibody response rates to measles, mumps, rubella, and varicella at Day 42 following Dose 2, to the same regimen in children of 12 months of age at the time of Dose 1.

The secondary study objectives are:

* To describe the antibody titres to measles, mumps, rubella and varicella at Day 42 following Dose 1 and Dose 2 of ProQuad® rHA administered to healthy children from 9 months of age.
* To evaluate the safety profile of Dose 1 and Dose 2 of ProQuad® rHA administered to healthy children from 9 months of age.


Eligibility criteria: Inclusion Criteria:

1. Healthy subject of either gender of 9 months of age
2. Negative clinical history of measles, mumps, rubella, varicella or zoster
3. Informed consent form signed by both parents or legal representative
4. Parent(s) or legal representative able to attend all the scheduled visits with the subject and to understand and comply with the study procedures
5. Both parent or legal representative are over 18 years of age
6. Subject is affiliated to a health social security system

Exclusion Criteria:

1. Febrile illness in the previous 3 days
2. Prior vaccination with a measles, mumps, rubella and/or varicella vaccine either alone or in any combination
3. Exposure to measles, mumps, rubella, varicella and/or zoster in the previous 30 days
4. Tuberculin test done in the previous 2 days
5. Severe chronic disease
6. Known active tuberculosis
7. Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition
8. Hereditary problems of fructose intolerance
9. Prior known sensitivity or allergy to any component of the vaccine
10. Known blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems
11. Humoral or cellular immunodeficiency,
12. Immunosuppressive therapy \[including systemic corticosteroids (a), given daily or on alternate days at high doses (\>=2 mg/kg/day prednisone equivalent or \>=20 mg/day if the subject's weight was \>10 kg) during at least 14 days in the previous 30 days\]
13. Family history of congenital or hereditary immunodeficiency
14. Receipt of immunoglobulins or blood-derived products in the previous 150 days or scheduled to be administered through Visit 5
15. Receipt of an inactivated vaccine in the previous 14 days
16. Receipt of a live non-study vaccine in the previous 28 days
17. Any medical condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives
18. Current participation or scheduled participation in any other clinical study through Visit 5

Primary outcomes:
measure: Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2
timeFrame: Day 132 (6 weeks after ProQuad® Dose 2)
measure: Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2
timeFrame: Day 132 (6 weeks after ProQuad® Dose 2)
measure: Percentage of Participants With Solicited Injection-site Adverse Reactions
timeFrame: Day 1 to Day 4 (up to 4 days after ProQuad® Dose 1)
measure: Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions
timeFrame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)
measure: Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1
timeFrame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)
measure: Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C
timeFrame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)
Secondary outcomes:
measure: Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1
timeFrame: Day 42 (6 weeks after ProQuad® Dose 1)
measure: GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2
timeFrame: Day 132 (6 weeks after ProQuad® Dose 2)
measure: Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL
timeFrame: Day 132 (6 weeks after ProQuad® Dose 2)
measure: Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1
timeFrame: Day 42 (6 weeks after ProQuad® Dose 1)
measure: Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1
timeFrame: Up to Day 28 (up to 4 weeks after ProQuad® Dose 1)
measure: Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2
timeFrame: Day 132 (6 weeks after ProQuad® Dose 2)
Other outcomes:
Locations:
Study officials:
affiliation: SPMSD
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Becker T, Gajdos V, Fiquet A, Thomas S, Richard P, Baudin M. Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad((R))) in infants from 9 months of age. Vaccine. 2012 Apr 26;30(20):3082-9. doi: 10.1016/j.vaccine.2012.02.062. Epub 2012 Mar 7.