Concomitant Use of Hepatitis A Vaccine With Measles, Mumps, Rubella and Varicella Vaccine and Pneumococcal 7-Valent Conjugate Vaccine in Healthy 12-Month-Old Children - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment
Condition:	Hepatitis A Virus
Interventions:	Biological: Comparator: VAQTA™ (Hepatitis A vaccine) Biological: Comparator: ProQuad™ (Measles, Mumps, Rubella and Varicella vaccine) Biological: Comparator: Prevnar™ (Pneumococcal 7-Valent Conjugate vaccine)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
39 clinical sites in the United States Date first participant visit: 14-Apr-2006 Date last participant visit: 25-Mar-2008

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

39 clinical sites in the United States

Date first participant visit: 14-Apr-2006

Date last participant visit: 25-Mar-2008

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Arm 1: VAQTA™ + ProQuad™ + Prevnar™	VAQTA™ (hepatitis A vaccine) + ProQuad™ (measles, mumps, rubella, and varicella vaccine) + Prevnar™ (pneumococcal 7-valent conjugate vaccine) administered at the same time at first study visit. Second doses of VAQTA™ and ProQuad™ administered together 24 weeks later at third study visit.
Arm 2: VAQTA™ Separate From ProQuad™ and Prevnar™	VAQTA™ (hepatitis A vaccine) dose 1 administered separately from ProQuad™ (measles, mumps, rubella, and varicella vaccine) and Prevnar™ (pneumococcal 7-valent conjugate vaccine). A second dose of VAQTA™ administered 24 weeks after the first dose at third study visit.

Participant Flow: Overall Study

	Arm 1: VAQTA™ + ProQuad™ + Prevnar™	Arm 2: VAQTA™ Separate From ProQuad™ and Prevnar™
STARTED	330	323
Visit 1	330	323
Visit 2	305	294
Visit 3	273	261
Visit 4	262	240
COMPLETED	262	230
NOT COMPLETED	68	93
Adverse Event	0	1
Lost to Follow-up	25	42
Protocol Violation	3	8
Withdraw by Participant	20	20
Participant Moved	11	10
Unspecified	9	12

	Arm 1: VAQTA™ + ProQuad™ + Prevnar™	Arm 2: VAQTA™ Separate From ProQuad™ and Prevnar™	Total
Number of Participants [units: participants]	330	323	653
Age [units: years] Mean ± Standard Deviation	12.4 ± 0.80	12.5 ± 0.89	12.4 ± 0.85
Gender [units: participants]
Female	156	166	322
Male	174	157	331

Outcome Measures

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1. Primary:

Antibody Response to Hepatitis A - Participants With a Serological Response [ 4 weeks Postdose 2 of hepatitis A vaccine (VAQTA™) ]

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2. Primary:

Antibody Response to Varicella - Participants With a Serological Response [ 6 weeks Postdose 1 of varicella-containing vaccine (ProQuad™) ]

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3. Primary:

Antibody Response to S. Pneumoniae Serotype 4 - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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4. Primary:

Antibody Response to S. Pneumoniae Serotype 6B - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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5. Primary:

Antibody Response to S. Pneumoniae Serotype 9V - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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6. Primary:

Antibody Response to S. Pneumoniae Serotype 14 - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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7. Primary:

Antibody Response to S. Pneumoniae Serotype 18C - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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8. Primary:

Antibody Response to S. Pneumoniae Serotype 19F - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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9. Primary:

Antibody Response to S. Pneumoniae Serotype 23F - Participants With a Serological Response [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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10. Primary:

Participants With 1 or More Systemic Adverse Experience [ 6 weeks post dose 1 ]

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11. Primary:

Participants With 1 or More Systemic Adverse Experience [ 4 weeks post dose 2 ]

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12. Primary:

Participants With 1 or More Systemic Adverse Experience. [ 6 months ]

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13. Primary:

Participants With 1 or More Injection-site Adverse Experience [ 6 weeks post dose 1 ]

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14. Primary:

Participants With 1 or More Injection-site Adverse Experience [ 4 weeks post dose 2 ]

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15. Primary:

Participants With 1 or More Injection-site Adverse Experience [ 6 months ]

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16. Primary:

Participants With Elevated Temperature (≥102.2F/ ≥39.0C) [ 6 weeks post dose 1 ]

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17. Primary:

Participants With Elevated Temperature (≥102.2F/ ≥39.0C) [ 4 weeks post dose 2 ]

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18. Primary:

Participants With Elevated Temperature (≥102.2F/ ≥39.0C) [ 6 months ]

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19. Primary:

Participants With 1 or More Serious Vaccine-related Adverse Experience [ 6 weeks post dose 1 ]

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20. Primary:

Participants With 1 or More Serious Vaccine-related Adverse Experience [ 4 weeks post dose 2 ]

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21. Primary:

Participants With 1 or More Serious Vaccine-related Adverse Experience [ 6 months ]

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22. Primary:

Antibody Response to Hepatitis A – Geometric Mean Titer [ 4 weeks Postdose 2 of hepatitis A vaccine (VAQTA™) ]

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23. Primary:

Antibody Response to Varicella - Geometric Mean Titer [ 6 weeks Postdose 1 of varicella-containing vaccine (ProQuad™) ]

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24. Primary:

Antibody Response to S. Pneumoniae Serotype 4 - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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25. Primary:

Antibody Response to S. Pneumoniae Serotype 6B - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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26. Primary:

Antibody Response to S. Pneumoniae Serotype 9V - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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27. Primary:

Antibody Response to S. Pneumoniae Serotype 14 - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

Show Outcome Measure 27

28. Primary:

Antibody Response to S. Pneumoniae Serotype 18C - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

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Measure Type	Primary
Measure Title	Antibody Response to S. Pneumoniae Serotype 18C - Geometric Mean Titer
Measure Description	Postvaccination observed Geometric Mean Titer of antibody to S. Pneumoniae serotype 18C
Time Frame	6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per-protocol analysis set includes participants who received Prevnar™ (pneumococcal 7-valent conjugate vaccine), had a postvaccination serology result, and followed the protocol procedures. Serotype 18C is one of 7 individual serotypes in Prevnar™

Reporting Groups

	Description
Arm 1: VAQTA™ + ProQuad™ + Prevnar™	VAQTA™ (hepatitis A vaccine) + ProQuad™ (measles, mumps, rubella, and varicella vaccine) + Prevnar™ (pneumococcal 7-valent conjugate vaccine) administered at the same time at first study visit. Second doses of VAQTA™ and ProQuad™ administered together 24 weeks later at third study visit.
Arm 2: VAQTA™ Separate From ProQuad™ and Prevnar™	VAQTA™ (hepatitis A vaccine) dose 1 administered separately from ProQuad™ (measles, mumps, rubella, and varicella vaccine) and Prevnar™ (pneumococcal 7-valent conjugate vaccine). A second dose of VAQTA™ administered 24 weeks after the first dose at third study visit.

Measured Values

	Arm 1: VAQTA™ + ProQuad™ + Prevnar™	Arm 2: VAQTA™ Separate From ProQuad™ and Prevnar™
Number of Participants Analyzed [units: participants]	247	247
Antibody Response to S. Pneumoniae Serotype 18C - Geometric Mean Titer [units: mcg/mL] Geometric Mean ( 95% Confidence Interval )	2.9 ( 2.6 to 3.3 )	2.6 ( 2.3 to 3.0 )

Statistical Analysis 1 for Antibody Response to S. Pneumoniae Serotype 18C - Geometric Mean Titer

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	ANCOVA
P Value ^[4]	<0.001
Mean difference in log titer ^[5]	1.1
Standard Deviation	± 0.2
95% Confidence Interval	( 0.9 to 1.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of the fold-difference of estimated GMTs of Arm 1 and Arm 2.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Similarity (non-inferiority) based on lower bound of the 2-sided 95% CI on the fold-difference of GMTs excluding a decrease of 2 fold or more (lower bound >0.5).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimated responses and their fold-difference were based on statistical analysis models adjusting for combined study center and prevaccination titer.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Similarity (non-inferiority) indicated that the fold difference was statistically significantly less than the prespecified clinically relevant 2-fold difference at the 1-sided α=0.025 level.
[5]	Other relevant estimation information:
	Fold-difference of estimated GMTs of Arm 1 and Arm 2.

29. Primary:

Antibody Response to S. Pneumoniae Serotype 19F - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

Show Outcome Measure 29

30. Primary:

Antibody Response to S. Pneumoniae Serotype 23F - Geometric Mean Titer [ 6 weeks Postvaccination of pneumococcal 7-valent conjugate vaccine (Prevnar™) ]

Show Outcome Measure 30

Responsible Party:	Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers:	2005_075, V251-067
Study First Received:	April 7, 2006
Results First Received:	March 24, 2009
Last Updated:	November 2, 2009
ClinicalTrials.gov Identifier:	NCT00312858 History of Changes
Health Authority:	United States: Food and Drug Administration