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)

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00325130

Enrollment

1042

Registered

2006-05-12

Start date

2006-04-30

Completion date

2007-04-30

Last updated

2015-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diphtheria, Meningitis, Neoplasms, Glandular and Epithelial, Tetanus, Whooping Cough

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.

Interventions

BIOLOGICALComparator: 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.

BIOLOGICALComparator: Menactra™ (Concomitant)

A single administration of 0.5 mL intramuscular injection in a limb opposite that of quadrivalent HPV injection at Day 1

BIOLOGICALComparator: Adacel™ (Concomitant)

a single administration of 0.5 mL intramuscular injection administered in a limb opposite that of quadrivalent HPV injection at Day 1

BIOLOGICALComparator: Menactra™ (Non-concomitant)

A single administration of 0.5 mL intramuscular injection in a limb opposite that of quadrivalent HPV injection at Month 1

BIOLOGICALComparator: Adacel™

A single administration of 0.5 mL intramuscular injection in a limb opposite that of quadrivalent HPV injection at Month 1

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

11 Years to 17 Years

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

Design outcomes

Primary

Measure	Time frame
Geometric Mean Titers (GMTs) for Pertussis Anti-Fimbrial Agglutinogens 2/3 (Anti-FIM) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	7 Months
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
Number of Subjects Who Seroconverted for HPV Type 11 (HPV 11 ≥ 16 mMU/mL) by Week 4 Postdose 3 (7 Months)	7 Months
Number of Subjects Who Seroconverted for HPV Type 16 (HPV 16 ≥ 20 mMU/mL) by Week 4 Postdose 3 (7 Months)	7 Months
Number of Subjects Who Seroconverted for HPV Type 18 (HPV 18≥ 24 mMU/mL) by Week 4 Postdose 3 (7 Months)	7 Months
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
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
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
Number of Subjects Who Achieved a Four-fold Rise in Titers to Meningococcal Serogroup Y One Month Postvaccination With Menactra™	7 Months
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
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
Geometric Mean Titers (GMTs) for Anti-HPV 6 at Week 4 Postdose 3 (7 Months) of GARDASIL™	7 Months
Geometric Mean Titers (GMTs) for Anti-HPV 11 at Week 4 Postdose 3 (7 Months) of GARDASIL™	7 Months
Geometric Mean Titers (GMTs) for Anti-HPV 16 at Week 4 Postdose 3 (7 Months) of GARDASIL™	7 Months
Geometric Mean Titers (GMTs) for Anti-HPV 18 at Week 4 Postdose 3 (7 Months) of GARDASIL™	7 Months
Geometric Mean Titers (GMTs) for Pertussis Anti-Pertussis Toxin (Anti-PT) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	7 Months
Geometric Mean Titers (GMTs) for Pertussis Anti-Filamentous Hemagglutinin) (Anti-FHA) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	7 Months
Geometric Mean Titers (GMTs) for Pertussis Anti Pertactin (Anti-PRN) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	7 Months

Secondary

Measure	Time frame
Acceptable Safety Profile	15 days post injection

Participant flow

Participants by arm

Arm	Count
Concomitant Administration Concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	518
Non-concomitant Administration Non-concomitant administration of quadrivalent HPV vaccine and Menactra™ and ADACEL™	524
Total	1,042

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	6	14
Overall Study	Moved	0	1
Overall Study	Patient Discontinued for Other	1	0
Overall Study	Protocol Deviation	0	1
Overall Study	Withdrawal by Subject	12	14

Baseline characteristics

Characteristic	Concomitant Administration	Non-concomitant Administration	Total
Age, Continuous	12.5 years STANDARD_DEVIATION 1.84	12.7 years STANDARD_DEVIATION 1.9	12.6 years STANDARD_DEVIATION 1.88
Age, Customized 10 to 17 Years of Age	518 participants	524 participants	1042 participants
Age, Customized 9 Years of Age and Under	0 participants	0 participants	0 participants
Age, Customized Over 17 Years of Age	0 participants	0 participants	0 participants
Race/Ethnicity Asian	5 participants	7 participants	12 participants
Race/Ethnicity Black	54 participants	74 participants	128 participants
Race/Ethnicity Hispanic American	42 participants	29 participants	71 participants
Race/Ethnicity Indian	1 participants	1 participants	2 participants
Race/Ethnicity Multi-Racial	9 participants	6 participants	15 participants
Race/Ethnicity Native American	1 participants	3 participants	4 participants
Race/Ethnicity White	406 participants	404 participants	810 participants
Sex: Female, Male Female	308 Participants	340 Participants	648 Participants
Sex: Female, Male Male	210 Participants	184 Participants	394 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	475 / —	448 / —
serious Total, serious adverse events	0 / —	2 / —

Outcome results

Primary

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

Time frame: 7 Months

Population: 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	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 11 at Week 4 Postdose 3 (7 Months) of GARDASIL™	1609.6 mMU/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 11 at Week 4 Postdose 3 (7 Months) of GARDASIL™	1513.7 mMU/mL

p-value: <0.001ANOVA

Primary

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

Time frame: 7 Months

Population: 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	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 16 at Week 4 Postdose 3 (7 Months) of GARDASIL™	7203.0 mMU/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 16 at Week 4 Postdose 3 (7 Months) of GARDASIL™	7370.0 mMU/mL

p-value: <0.001ANOVA

Primary

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

Time frame: 7 Months

Population: 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	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 18 at Week 4 Postdose 3 (7 Months) of GARDASIL™	1270.2 mMU/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 18 at Week 4 Postdose 3 (7 Months) of GARDASIL™	1425.3 mMU/mL

p-value: <0.001ANOVA

Primary

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

Time frame: 7 Months

Population: 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	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 6 at Week 4 Postdose 3 (7 Months) of GARDASIL™	1349.3 mMU/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Anti-HPV 6 at Week 4 Postdose 3 (7 Months) of GARDASIL™	1340.8 mMU/mL

p-value: <0.001ANOVA

Primary

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

Time frame: 7 Months

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

Arm	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti-Filamentous Hemagglutinin) (Anti-FHA) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	132.5 ELISA units/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti-Filamentous Hemagglutinin) (Anti-FHA) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	150.9 ELISA units/mL

p-value: <0.001ANOVA

Primary

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti-Fimbrial Agglutinogens 2/3 (Anti-FIM) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	703.0 ELISA units/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti-Fimbrial Agglutinogens 2/3 (Anti-FIM) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	611.2 ELISA units/mL

p-value: <0.001ANOVA

Primary

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

Time frame: 7 Months

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

Arm	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti Pertactin (Anti-PRN) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	253.6 ELISA units/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti Pertactin (Anti-PRN) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	274.2 ELISA units/mL

p-value: <0.001ANOVA

Primary

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

Time frame: 7 Months

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

Arm	Measure	Value (GEOMETRIC_MEAN)
Concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti-Pertussis Toxin (Anti-PT) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	18.5 ELISA units/mL
Non-concomitant Administration	Geometric Mean Titers (GMTs) for Pertussis Anti-Pertussis Toxin (Anti-PT) One Month Postvaccination (Week 4 Postdose 1) With ADACEL™	19.3 ELISA units/mL

p-value: <0.001ANOVA

Primary

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

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

Arm	Measure	Value (NUMBER)
Concomitant Administration	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™	397 Participants
Non-concomitant Administration	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™	381 Participants