Back to resultsComparative Study of Immunogenicity and Safety of a 2-dose Regimen of ProQuad® Manufactured With rHA (V221-038)
Primary Purpose
Measles, Mumps, Rubella
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ProQuad® manufactured with recombinant Human Albumin (rHA)
Sponsored by
About this trial
This is an interventional prevention trial for Measles
Eligibility Criteria
Inclusion Criteria:
- Healthy subject of either gender of 9 months of age
- Negative clinical history of measles, mumps, rubella, varicella or zoster
- Informed consent form signed by both parents or legal representative
- Parent(s) or legal representative able to attend all the scheduled visits with the subject and to understand and comply with the study procedures
- Both parent or legal representative are over 18 years of age
- Subject is affiliated to a health social security system
Exclusion Criteria:
- Febrile illness in the previous 3 days
- Prior vaccination with a measles, mumps, rubella and/or varicella vaccine either alone or in any combination
- Exposure to measles, mumps, rubella, varicella and/or zoster in the previous 30 days
- Tuberculin test done in the previous 2 days
- Severe chronic disease
- Known active tuberculosis
- Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition
- Hereditary problems of fructose intolerance
- Prior known sensitivity or allergy to any component of the vaccine
- Known blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems
- Humoral or cellular immunodeficiency,
- 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]
- Family history of congenital or hereditary immunodeficiency
- Receipt of immunoglobulins or blood-derived products in the previous 150 days or scheduled to be administered through Visit 5
- Receipt of an inactivated vaccine in the previous 14 days
- Receipt of a live non-study vaccine in the previous 28 days
- Any medical condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives
- Current participation or scheduled participation in any other clinical study through Visit 5
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Arm 1: ProQuad® at 9 and 12 months
Arm 2: ProQuad® at 11 and 14 months
Arm 3: ProQuad at 12 and 15 months
Arm Description
Pediatric participants received ProQuad® Dose 1 at 9 months of age and ProQuad® Dose 2 at 12 months of age.
Pediatric participants received ProQuad® Dose 1 at 11 months of age and ProQuad® Dose 2 at 14 months of age.
Pediatric participants received ProQuad® Dose 1 at 12 months of age and ProQuad® Dose 2 at 15 months of age.
Outcomes
Primary Outcome Measures
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.
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.
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.
Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions
The percentage of participants with unsolicited injection-site reactions after ProQuad® Dose 1 was determined.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1
The percentage of participants with rashes of interest after ProQuad® Dose 1 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash.
Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2
The percentage of participants with rashes of interest after receiving ProQuad® Dose 2 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash.
Full Information
NCT ID
NCT00566527
First Posted
November 29, 2007
Last Updated
January 3, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00566527
Brief Title
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
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
November 29, 2007 (Actual)
Primary Completion Date
December 29, 2008 (Actual)
Study Completion Date
December 29, 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Measles, Mumps, Rubella, Varicella
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1620 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: ProQuad® at 9 and 12 months
Arm Type
Experimental
Arm Description
Pediatric participants received ProQuad® Dose 1 at 9 months of age and ProQuad® Dose 2 at 12 months of age.
Arm Title
Arm 2: ProQuad® at 11 and 14 months
Arm Type
Experimental
Arm Description
Pediatric participants received ProQuad® Dose 1 at 11 months of age and ProQuad® Dose 2 at 14 months of age.
Arm Title
Arm 3: ProQuad at 12 and 15 months
Arm Type
Active Comparator
Arm Description
Pediatric participants received ProQuad® Dose 1 at 12 months of age and ProQuad® Dose 2 at 15 months of age.
Intervention Type
Biological
Intervention Name(s)
ProQuad® manufactured with recombinant Human Albumin (rHA)
Intervention Description
A 2-dose regimen of ProQuad® (0.5 mL per dose) given via subcutaneous injection into the deltoid muscle at a 3-month interval. Each dose contains measles virus Enders' Edmonston strain (live attenuated), mumps virus Jeryl Lynn™ (Level B) strain (live attenuated), rubella virus Wistar RA 27 or 3 strain (live attenuated), and varicella virus Oka or Merck strain (live attenuated).
Primary Outcome Measure Information:
Title
Percentage of Participants in Arm 2 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2
Description
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)
Title
Percentage of Participants in Arm 1 and Arm 3 Meeting Antibody Immunogenicity Response Criteria Following ProQuad® Dose 2
Description
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)
Title
Percentage of Participants With Solicited Injection-site Adverse Reactions
Description
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)
Title
Percentage of Participants Experiencing Unsolicited Injection-site Adverse Reactions
Description
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)
Title
Percentage of Participants Experiencing a Systemic Adverse Event After ProQuad® Dose 1
Description
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)
Title
Percentage of Participants With Rectal (or Rectal Equivalent) Temperature ≥ 39.4°C
Description
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 Outcome Measure Information:
Title
Geometric Mean Titres (GMT) to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 1
Description
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)
Title
GMT to Measles, Mumps, Rubella, and Varicella After ProQuad® Dose 2
Description
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)
Title
Percentage of Participants With Varicella Antibody Titre ≥ 1.25 gpELISA Units/mL
Description
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)
Title
Percentage of Baseline Seronegative Participants Meeting Antibody Immunogenicity Response Criteria After ProQuad® Dose 1
Description
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)
Title
Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 1
Description
The percentage of participants with rashes of interest after ProQuad® Dose 1 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash.
Time Frame
Up to Day 28 (up to 4 weeks after ProQuad® Dose 1)
Title
Percentage of Participants With Non-injection Site Rashes of Interest Following ProQuad® Dose 2
Description
The percentage of participants with rashes of interest after receiving ProQuad® Dose 2 was determined. Rashes of interest consisted of measles-like rash, rubella-like rash, varicella-like rash, zoster-like rash, and mumps-like rash.
Time Frame
Day 132 (6 weeks after ProQuad® Dose 2)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
9 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy subject of either gender of 9 months of age
Negative clinical history of measles, mumps, rubella, varicella or zoster
Informed consent form signed by both parents or legal representative
Parent(s) or legal representative able to attend all the scheduled visits with the subject and to understand and comply with the study procedures
Both parent or legal representative are over 18 years of age
Subject is affiliated to a health social security system
Exclusion Criteria:
Febrile illness in the previous 3 days
Prior vaccination with a measles, mumps, rubella and/or varicella vaccine either alone or in any combination
Exposure to measles, mumps, rubella, varicella and/or zoster in the previous 30 days
Tuberculin test done in the previous 2 days
Severe chronic disease
Known active tuberculosis
Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition
Hereditary problems of fructose intolerance
Prior known sensitivity or allergy to any component of the vaccine
Known blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems
Humoral or cellular immunodeficiency,
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]
Family history of congenital or hereditary immunodeficiency
Receipt of immunoglobulins or blood-derived products in the previous 150 days or scheduled to be administered through Visit 5
Receipt of an inactivated vaccine in the previous 14 days
Receipt of a live non-study vaccine in the previous 28 days
Any medical condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives
Current participation or scheduled participation in any other clinical study through Visit 5
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
SPMSD
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22406278
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.
Results Reference
derived
Learn more about this trial
Comparative Study of Immunogenicity and Safety of a 2-dose Regimen of ProQuad® Manufactured With rHA (V221-038)
We'll reach out to this number within 24 hrs