Concomitant Use of Gardasil (V501) (Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine) With Combined Diphtheria, Tetanus, Pertussis Vaccine and Meningococcal Conjugate Vaccine in Adolescents (V501-025)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00325130
• Collaborator: (none)
• Enrollment: 1,042
• Arms: 2
• Duration (Months): 12

Study Details

Study Description

Brief Summary

Data from this study are expected to demonstrate that V501 (Human Papillomavirus (HPV) [Types 6, 11, 16, 18] Recombinant Vaccine) , when administered concomitantly with a combined diphtheria, tetanus, pertussis (Tdap) vaccine and a meningococcal conjugate vaccine in adolescents remains immunogenic and well-tolerated and it does not impair the immunogenicity of the concomitant vaccines.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Glandular and Epithelial; Diphtheria; Tetanus; Whooping Cough; Meningitis	Biological: Comparator: Quadrivalent Human Papillomavirus (HPV) vaccine; Biological: Comparator: Menactra™ (Concomitant); Biological: Comparator: Adacel™ (Concomitant); Biological: Comparator: Menactra™ (Non-concomitant); Biological: Comparator: Adacel™	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1042 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: An Open-Label, Randomized, Multicenter Study of the Safety, Tolerability, and Immunogenicity of V501 Given Concomitantly With Menactra™ and ADACEL™ in Healthy Adolescents 11-17 Years of Age
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Apr 1, 2007
• Actual Study Completion Date: Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Concomitant Administration	Biological: Comparator: Quadrivalent Human Papillomavirus (HPV) vaccine; Quadrivalent HPV vaccine was provided by the SPONSOR in single-dose vials containing a volume of 0.75 mL. The vaccine was administered as a 0.5-mL intramuscular dose at Day 1, Month 2, and Month 6.; Other Names: Gardasil ; Biological: Comparator: Menactra™ (Concomitant); A single administration of 0.5 mL intramuscular injection in a limb opposite that of quadrivalent HPV injection at Day 1; Biological: Comparator: Adacel™ (Concomitant); a single administration of 0.5 mL intramuscular injection administered in a limb opposite that of quadrivalent HPV injection at Day 1
Experimental: Group 2 Non-concomitant administration	Biological: Comparator: Quadrivalent Human Papillomavirus (HPV) vaccine; Quadrivalent HPV vaccine was provided by the SPONSOR in single-dose vials containing a volume of 0.75 mL. The vaccine was administered as a 0.5-mL intramuscular dose at Day 1, Month 2, and Month 6.; Other Names: Gardasil ; Biological: Comparator: Menactra™ (Non-concomitant); A single administration of 0.5 mL intramuscular injection in a limb opposite that of quadrivalent HPV injection at Month 1; Biological: Comparator: Adacel™; A single administration of 0.5 mL intramuscular injection in a limb opposite that of quadrivalent HPV injection at Month 1

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Seroconverted for Human Papillomavirus (HPV) Type 6 (HPV 6 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months) [7 Months]

2. Number of Subjects Who Seroconverted for HPV Type 11 (HPV 11 ≥ 16 mMU/mL) by Week 4 Postdose 3 (7 Months) [7 Months]

3. Number of Subjects Who Seroconverted for HPV Type 16 (HPV 16 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months) [7 Months]

4. Number of Subjects Who Seroconverted for HPV Type 18 (HPV 18≥ 24 mMU/mL) by Week 4 Postdose 3 (7 Months) [7 Months]

5. Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup A One Month Postvaccination (Week 4 Postdose 1) With Menactra™ [7 Months]

6. Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup C One Month Postvaccination (Week 4 Postdose 1) With Menactra™ [7 Months]

7. Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup W-135 One Month Postvaccination (Week 4 Postdose 1) With Menactra™ [7 Months]

8. Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup Y One Month Postvaccination With Menactra™ [7 Months]

9. Number of Subjects Who Achieved Acceptable Levels of Titers (Diphtheria ≥ 0.1 IU/mL) to Diphtheria One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [7 Months]

10. Number of Subjects Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥ 0.1 IU/mL) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [7 Months]

11. Geometric Mean Titers (GMTs) for Anti-HPV 6 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [7 Months]

12. Geometric Mean Titers (GMTs) for Anti-HPV 11 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [7 Months]

13. Geometric Mean Titers (GMTs) for Anti-HPV 16 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [7 Months]

14. Geometric Mean Titers (GMTs) for Anti-HPV 18 at Week 4 Postdose 3 (7 Months) of GARDASIL™ [7 Months]

15. Geometric Mean Titers (GMTs) for Pertussis Anti-Pertussis Toxin (Anti-PT) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [7 Months]

16. Geometric Mean Titers (GMTs) for Pertussis Anti-Filamentous Hemagglutinin) (Anti-FHA) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [7 Months]

17. Geometric Mean Titers (GMTs) for Pertussis Anti Pertactin (Anti-PRN) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [7 Months]

18. Geometric Mean Titers (GMTs) for Pertussis Anti-Fimbrial Agglutinogens 2/3 (Anti-FIM) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™ [7 Months]

Secondary Outcome Measures

1. Acceptable Safety Profile [15 days post injection]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 11 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Must be healthy boys or girls, 11-17 years of age

• Must be a virgin with no intention of becoming sexually active during the study period

• Must have been properly vaccinated against diphtheria, tetanus and pertussis

Exclusion Criteria:

• Must not have received a vaccine against diphtheria, tetanus and pertussis in the past 5 years

• Must not have received any prior human papillomavirus (HPV) vaccine or meningococcal vaccine

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00325130
• Other Study ID Numbers: V501-025; 2005_092
• First Posted: May 12, 2006
• Last Update Posted: Mar 12, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Tetanus; Diphtheria; Whooping Cough; Neoplasms, Glandular and Epithelial; Meningitis

Study Results

Participant Flow

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Period Title: Overall Study
STARTED	518	524
COMPLETED	499	494
NOT COMPLETED	19	30

Baseline Characteristics

Arm/Group Title	Concomitant Administration	Non-concomitant Administration	Total
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Total of all reporting groups
Overall Participants	518	524	1042
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.5 (1.84)	12.7 (1.90)	12.6 (1.88)
Age, Customized (participants) [Number]
9 Years of Age and Under	0 0%	0 0%	0 0%
10 to 17 Years of Age	518 100%	524 100%	1042 100%
Over 17 Years of Age	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	308 59.5%	340 64.9%	648 62.2%
Male	210 40.5%	184 35.1%	394 37.8%
Race/Ethnicity (participants) [Number]
Asian	5 1%	7 1.3%	12 1.2%
Black	54 10.4%	74 14.1%	128 12.3%
Hispanic American	42 8.1%	29 5.5%	71 6.8%
Indian	1 0.2%	1 0.2%	2 0.2%
Multi-Racial	9 1.7%	6 1.1%	15 1.4%
Native American	1 0.2%	3 0.6%	4 0.4%
White	406 78.4%	404 77.1%	810 77.7%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Seroconverted for Human Papillomavirus (HPV) Type 6 (HPV 6 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months)
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	418	418
Number [Participants]	416 80.3%	417 79.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -5%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

2. Secondary Outcome

Title	Acceptable Safety Profile
Time Frame	15 days post injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Primary Outcome

Title	Number of Subjects Who Seroconverted for HPV Type 11 (HPV 11 ≥ 16 mMU/mL) by Week 4 Postdose 3 (7 Months)
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	418	418
Number [Participants]	418 80.7%	418 79.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -5%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

4. Primary Outcome

Title	Number of Subjects Who Seroconverted for HPV Type 16 (HPV 16 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months)
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	421	420
Number [Participants]	421 81.3%	420 80.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -5%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

5. Primary Outcome

Title	Number of Subjects Who Seroconverted for HPV Type 18 (HPV 18≥ 24 mMU/mL) by Week 4 Postdose 3 (7 Months)
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	423	421
Number [Participants]	421 81.3%	420 80.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -5%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

6. Primary Outcome

Title	Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup A One Month Postvaccination (Week 4 Postdose 1) With Menactra™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	424	412
Number [Participants]	367 70.8%	345 65.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -10%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

7. Primary Outcome

Title	Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup C One Month Postvaccination (Week 4 Postdose 1) With Menactra™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	451	422
Number [Participants]	423 81.7%	394 75.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -10%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

8. Primary Outcome

Title	Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup W-135 One Month Postvaccination (Week 4 Postdose 1) With Menactra™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	446	415
Number [Participants]	429 82.8%	394 75.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -10%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

9. Primary Outcome

Title	Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup Y One Month Postvaccination With Menactra™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	439	427
Number [Participants]	414 79.9%	404 77.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -10%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

10. Primary Outcome

Title	Number of Subjects Who Achieved Acceptable Levels of Titers (Diphtheria ≥ 0.1 IU/mL) to Diphtheria One Month Postvaccination (Week 4 Postdose 1) With ADACEL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	398	381
Number [Participants]	397 76.6%	381 72.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -10%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

11. Primary Outcome

Title	Number of Subjects Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥ 0.1 IU/mL) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	398	384
Number [Participants]	398 76.8%	384 73.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in seroconversion rates (concomitant group - nonconcomitant group) must be greater than -10%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	Miettinen & Nurminen
	Comments	Miettinen & Nurminen method for difference in proportions, Stat Med 1985;4:213-26

12. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Anti-HPV 6 at Week 4 Postdose 3 (7 Months) of GARDASIL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	418	418
Geometric Mean (95% Confidence Interval) [mMU/mL]	1349.3	1340.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.5.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

13. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Anti-HPV 11 at Week 4 Postdose 3 (7 Months) of GARDASIL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	418	418
Geometric Mean (95% Confidence Interval) [mMU/mL]	1609.6	1513.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.5.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

14. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Anti-HPV 16 at Week 4 Postdose 3 (7 Months) of GARDASIL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	421	420
Geometric Mean (95% Confidence Interval) [mMU/mL]	7203.0	7370.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.5.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

15. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Anti-HPV 18 at Week 4 Postdose 3 (7 Months) of GARDASIL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	423	421
Geometric Mean (95% Confidence Interval) [mMU/mL]	1270.2	1425.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.5.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

16. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Pertussis Anti-Pertussis Toxin (Anti-PT) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	425	391
Geometric Mean (95% Confidence Interval) [ELISA units/mL]	18.5	19.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.67.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

17. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Pertussis Anti-Filamentous Hemagglutinin) (Anti-FHA) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	430	402
Geometric Mean (95% Confidence Interval) [ELISA units/mL]	132.5	150.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.67.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

18. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Pertussis Anti Pertactin (Anti-PRN) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	430	402
Geometric Mean (95% Confidence Interval) [ELISA units/mL]	253.6	274.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.67.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

19. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Pertussis Anti-Fimbrial Agglutinogens 2/3 (Anti-FIM) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations and must have post-vaccination data.

Arm/Group Title	Concomitant Administration	Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
Measure Participants	430	402
Geometric Mean (95% Confidence Interval) [ELISA units/mL]	703.0	611.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concomitant Administration, Non-concomitant Administration
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ratio of GMTs (concomitant group / nonconcomitant group) must be greater than 0.67.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Since p<0.05, the hypothesis of noninferiority is accepted for this outcome.
	Method	ANOVA
	Comments	ANOVA on natural log titer with fixed effects for region, vaccination group and their interaction.

Adverse Events

Arm/Group Title	Concomitant Administration		Non-concomitant Administration
Arm/Group Description	Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™		Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™
All Cause Mortality
	Concomitant Administration		Non-concomitant Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Concomitant Administration		Non-concomitant Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/ (NaN)		2/ (NaN)
General disorders
Parotidectomy	0/522 (0%)		1/498 (0.2%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/522 (0%)		1/498 (0.2%)
Other (Not Including Serious) Adverse Events
	Concomitant Administration		Non-concomitant Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	475/ (NaN)		448/ (NaN)
Gastrointestinal disorders
Abdominal Pain Upper	27/520 (5.2%)		26/498 (5.2%)
General disorders
Injection Site Pain quadrivalent HPV Vaccine postvaccination 1	315/514 (61.3%)		228/406 (56.2%)
Injection Site Swelling HPV Vaccine postvaccination 1	56/514 (10.9%)		28/406 (6.9%)
Injection Site Erythema qHPV Vaccine (postvaccination 2)	53/506 (10.5%)		61/492 (12.4%)
Injection Site Pain qHPV Vaccine (postvaccination 2)	210/506 (41.5%)		194/492 (39.4%)
Injection Site Erythema qHPV Vaccine (postvaccination 3)	68/503 (13.5%)		60/485 (12.4%)
Injection Site Pain qHPV Vaccine (postvaccination 3)	253/503 (50.3%)		234/485 (48.2%)
Injection Site Swelling qHPV Vaccine (postvaccination 3)	52/503 (10.3%)		55/485 (11.3%)
Injection Site Erythema ADACEL™ + Menactra™	121/514 (23.5%)		107/401 (26.7%)
Injection Site Pain ADACEL™ + Menactra™	421/514 (81.9%)		303/401 (75.6%)
Injection Site Swelling ADACEL™ + Menactra™	145/514 (28.2%)		113/401 (28.2%)
Injection Site Erythema qHPV Vaccine (post-vaccination 1)	37/514 (7.2%)		26/406 (6.4%)
Injection Site Swelling qHPV Vaccine (post-vaccination 2)	42/506 (8.3%)		48/492 (9.8%)
Injection Site Bruising ADACEL™ + Menactra™	30/514 (5.8%)		9/401 (2.2%)
Pyrexia	45/520 (8.7%)		50/498 (10%)
Nervous system disorders
Headache Systemic Clinical	113/520 (21.7%)		114/498 (22.9%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain	26/520 (5%)		35/498 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.