Immunogenicity and Tolerability of V503 Versus GARDASIL (V503-009)

A Randomized, Double-Blinded, Controlled With GARDASIL (Human Papillomavirus Vaccine [Types 6, 11, 16, 18] (Recombinant, Adsorbed)), Phase III Clinical Trial to Study the Immunogenicity and Tolerability of V503 (9-Valent Human Papillomavirus (HPV) Vaccine) in Preadolescent and Adolescent Girls (9- to 15-year-old)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01304498

Enrollment

600

Registered

2011-02-25

Start date

2011-02-23

Completion date

2011-12-20

Last updated

2018-12-14

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

Conditions

Human Papillomavirus

Brief summary

Primary objective: • To demonstrate that administration of V503 induces non-inferior Geometric Mean Titers (GMTs) (for serum anti-HPV16 and anti-HPV18) compared to GARDASIL. Secondary objectives: * To evaluate the tolerability of V503 in 9-15 year-old girls. * To summarize humoral immune response (anti-HPV 6, 11, 16, 18) induced by V503 or GARDASIL.

Interventions

BIOLOGICALV503

9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine

BIOLOGICALGARDASIL

Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

9 Years to 15 Years

Healthy volunteers

Yes

Inclusion criteria

* Female from 9 to 15 years old. * Good physical health.

Exclusion criteria

* Known allergy to any vaccine component. * History of severe allergic reaction. * Thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. * Pregnant subject. * Immunocompromised or immunodeficient subject. * Splenectomy. * Receipt of medication / vaccine that may interfere with study assessment. * Fever * History of a positive test for HPV, prior receipt of HPV vaccine or prior participation to HPV trial. * Any condition that might interfere with study assessment.

Design outcomes

Primary

Measure	Time frame	Description
Geometric Mean Titers (GMTs) to HPV Types 16 and 18	4 weeks postdose 3 (Month 7)	Serum antibodies to HPV types 16 and 18 were measured with a Competitive Luminex Immunoassay.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	4 weeks postdose 3 (Month 7)	Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck Units/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24. The percentage of participants who were seropositive according to these cutoffs was assessed.
Percentage of Participants With One or More Adverse Events	Up to Month 7	An adverse event is defined as any unfavourable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine, is also an adverse event. The percentage of participants with one or more adverse events was assessed.
Percentage of Participants With One or More Injection-site Adverse Reactions	Up to 5 days after any vaccination	The percentage of participants with one or more injection-site adverse reactions (solicited or unsolicited) was assessed.
GMTs to HPV Types 6 and 11	4 weeks postdose 3 (Month 7)	Serum antibodies to HPV types 6 and 11 were measured with a Competitive Luminex Immunoassay.
Percentage of Participants With Maximum Oral Temperature ≥37.8°C	Up to 15 days after any vaccination	The percentage of participants with maximum oral temperature ≥37.8°C was assessed.
Percentage of Participants With One or More Serious Adverse Events	Up to Month 7	A serious adverse event is an adverse event that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or may jeopardize the participant and may require medical or surgical intervention. The percentage of participants with one or more serious adverse events was assessed.
Percentage of Participants With One or More Systemic Adverse Events	Up to 15 days after any vaccination	The percentage of participants with one or more systemic adverse events was assessed.

Participant flow

Recruitment details

A total of 603 participants were screened and 600 were randomized

Participants by arm

Arm	Count
V503 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	300
GARDASIL Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	300
Total	600

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	1
Overall Study	Lost to Follow-up	2	1
Overall Study	Protocol Violation	1	0
Overall Study	Withdrawal by Subject	2	3

Baseline characteristics

Characteristic	V503	GARDASIL	Total
Age, Continuous	12.6 Years STANDARD_DEVIATION 1.9	12.6 Years STANDARD_DEVIATION 1.9	12.6 Years STANDARD_DEVIATION 1.9
Age, Customized 13 to 15 years old	150 Participants	150 Participants	300 Participants
Age, Customized 9 to 12 years old	150 Participants	150 Participants	300 Participants
Sex: Female, Male Female	300 Participants	300 Participants	600 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	280 / 299	274 / 300
serious Total, serious adverse events	1 / 299	2 / 300

Outcome results

Primary

Geometric Mean Titers (GMTs) to HPV Types 16 and 18

Serum antibodies to HPV types 16 and 18 were measured with a Competitive Luminex Immunoassay.

Time frame: 4 weeks postdose 3 (Month 7)

Population: All randomized participants. The n values are participants who received all 3 vaccinations within acceptable day ranges, had Month 7 serology to the HPV type within acceptable day ranges, were seronegative to the HPV type at Day 1, and had no protocol violations that interfered with evaluation of immune response.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
V503	Geometric Mean Titers (GMTs) to HPV Types 16 and 18	HPV Type 16 (n=276, 270)	6739.5 milli Merck Units/mL
V503	Geometric Mean Titers (GMTs) to HPV Types 16 and 18	HPV Type 18 (n=276, 269)	1956.6 milli Merck Units/mL
GARDASIL	Geometric Mean Titers (GMTs) to HPV Types 16 and 18	HPV Type 16 (n=276, 270)	6887.4 milli Merck Units/mL
GARDASIL	Geometric Mean Titers (GMTs) to HPV Types 16 and 18	HPV Type 18 (n=276, 269)	1795.6 milli Merck Units/mL

Comparison: HPV Type 16p-value: <0.00195% CI: [0.85, 1.11]ANOVA

Comparison: HPV Type 18p-value: <0.00195% CI: [0.91, 1.29]ANOVA

Secondary

GMTs to HPV Types 6 and 11

Serum antibodies to HPV types 6 and 11 were measured with a Competitive Luminex Immunoassay.

Time frame: 4 weeks postdose 3 (Month 7)

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
V503	GMTs to HPV Types 6 and 11	HPV Type 6 (n=273, 261)	1679.4 milli Merck Units/mL
V503	GMTs to HPV Types 6 and 11	HPV Type 11 (n=273, 261)	1315.6 milli Merck Units/mL
GARDASIL	GMTs to HPV Types 6 and 11	HPV Type 6 (n=273, 261)	1565.9 milli Merck Units/mL
GARDASIL	GMTs to HPV Types 6 and 11	HPV Type 11 (n=273, 261)	1417.3 milli Merck Units/mL

Secondary

Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18

Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck Units/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24. The percentage of participants who were seropositive according to these cutoffs was assessed.

Time frame: 4 weeks postdose 3 (Month 7)

Arm	Measure	Group	Value (NUMBER)
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 6 (n=273, 261)	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 11 (n=273, 261)	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 16 (n=276, 270)	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 18 (n=276, 269)	100 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 18 (n=276, 269)	100 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 6 (n=273, 261)	100 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 16 (n=276, 270)	100 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18	HPV Type 11 (n=273, 261)	100 Percentage of participants

Secondary