Comparative Study of Immunogenicity and Safety of a 2-dose Regimen of ProQuad® Manufactured With rHA (V221-038)

Merck Sharp & Dohme LLC1,620 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 9 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2

Immunogenicity response rates were compared in participants with baseline seronegativity from Arm 2 (received ProQuad® Dose 1 at 11 months) and Arm 3 (received ProQuad® Dose 1 at 12 months). 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). 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.

Time frame: Day 132 (6 weeks after ProQuad® Dose 2)

Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2

Immunogenicity response rates were compared in participants with baseline seronegativity from Arm 1 (received ProQuad® Dose 1 at 9 months) and Arm 3 (received ProQuad® Dose 1 at 12 months). Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. 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.

Time frame: Day 132 (6 weeks after ProQuad® Dose 2)

Percentage of Participants With Solicited Injection-site Adverse Reactions

The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 1.

Time frame: Day 1 to Day 4 (up to 4 days after ProQuad® Dose 1)

Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions

The percentage of participants with unsolicited injection-site reactions after ProQuad® Dose 1 was determined.

Time frame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)

Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1

The percentage of participants with systemic adverse events after ProQuad® Dose 1 was determined.

Time frame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)

Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C

The percentage of participants with a rectal (or rectal equivalent) temperature ≥ 39.4°C after ProQuad® Dose 1 was determined.

Time frame: Up to Day 28 (up to 28 days after ProQuad® Dose 1)

Secondary Outcomes

Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1

Antibody titres (GMT) to measles, mumps, rubella, and varicella were determined after the first ProQuad® dose in participants with seronegative baseline values. Baseline seronegativity criteria were as follows: measles antibody titre \<255 mIU/mL; mumps antibody titre \<10 ELISA Ab units mL; rubella antibody titre \<10 IU/mL; and varicella antibody titre \<1.25 gpELISA units/mL.

Time frame: Day 42 (6 weeks after ProQuad® Dose 1)

GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2

Antibody titres (GMT) to measles, mumps, rubella, and varicella were determined after the second ProQuad® dose in participants with seronegative baseline values. Baseline seronegativity criteria were as follows: measles antibody titre \<255 mIU/mL; mumps antibody titre \<10 ELISA Ab units mL; rubella antibody titre \<10 IU/mL; and varicella antibody titre \<1.25 gpELISA units/mL.

Time frame: Day 132 (6 weeks after ProQuad® Dose 2)

Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL

The percentage of participants with varicella antibody titre ≥ 1.25 gpELISA units/mL 6 weeks after each ProQuad® dose was determined.

Time frame: Day 132 (6 weeks after ProQuad® Dose 2)

Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1

The percentage of baseline seronegative participants meeting measles, mumps, rubella, and varicella antibody response criteria after the first ProQuad® dose was determined. Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. 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.

Time frame: Day 42 (6 weeks after ProQuad® Dose 1)

Comparative Study of Immunogenicity and Safety of a 2-dose Regimen of ProQuad® Manufactured With rHA (V221-038)

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes