A Study to Compare Immune Response of V503 to Gardasil in 16- to 26-year-old Men (V503-020)

A Randomized, Double-Blinded, Controlled With GARDASIL (Human Papillomavirus Vaccine [HPV] [Types 6, 11, 16, 18] (Recombinant, Adsorbed)), Phase 3 Clinical Trial to Study the Immunogenicity and Tolerability of V503 (9-Valent Human Papillomavirus L1 Virus-Like Particle [VLP] Vaccine) in 16- to 26-year-old Men

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02114385

Enrollment

500

Registered

2014-04-15

Start date

2014-03-24

Completion date

2015-04-22

Last updated

2018-11-01

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

Conditions

Papilloma Viral Infection

Keywords

Prevention

Brief summary

Primary objective To demonstrate that administration of V503 induces non-inferior Geometric Mean Titres (GMTs) for serum anti-HPV 6, 11, 16, and 18, compared to GARDASIL in 16- to 26-year-old men

Detailed description

Secondary objectives * To evaluate the tolerability of V503 in 16- to 26-year-old men. * To summarise humoral immune responses, including anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 GMTs and seroconversion rates at 4 weeks post-dose 3, in 16- to 26-year-old men who received V503 or GARDASIL

Interventions

BIOLOGICALV503

9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection

BIOLOGICALGARDASIL

Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

16 Years to 26 Years

Healthy volunteers

Yes

Inclusion criteria

* Subject is a man, between the ages of 16 years and 0 days and 26 years and 364 days on the day of enrolment. * Subject is a man who has had no more than 5 lifetime female sexual partners. * Subject is judged to be in good physical health on the basis of medical history, physical examination, and laboratory results. * Subject, or subject's parent or guardian, fully understand study procedures, alternative treatments available, the risks involved with the study, and voluntarily agree to participate by giving written informed consent.

Exclusion criteria

* Subject who has had sex with a male partner. * Subject has a history of HPV-related external genital lesions or HPV-related anal lesions * Subject has a known allergy to any vaccine component, including aluminium, yeast, or BENZONASE * Subject has a history of severe allergic reaction that required medical intervention. * Subject has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. * Subject is concurrently enrolled in clinical studies of investigational medicinal products. * Subject has donated blood within 1 week prior to the Day 1 vaccination, or intends to donate during Day 1 through Month 7 of the study. * Subject is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition. * Subject has had a splenectomy. * Subject is receiving or has received in the year prior to enrolment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide, TNF-α antagonists, monoclonal antibody therapies, intravenous gamma globulin, antilymphocyte sera, or other therapy known to interfere with the immune response. * Subject has received any immune globulin product or blood-derived product within the 6 months prior to the Day 1 vaccination, or plans to receive any such product during Day 1 through Month 7 of the study. * Subject has received non-replicating (inactivated) vaccines within 14 days prior to the Day 1 vaccination or has received replicating (live) vaccines within 21 days prior to the Day 1 vaccination. * Subject has received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo. * Subject has had a fever within the 24-hour period prior to the Day 1 vaccination. * Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate. * Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study. * Subject is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or dependence. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use. * Subject, or subject's parent or guardian, is or has an immediate family member (spouse or children) who is investigational site or sponsor staff directly involved with this trial.

Design outcomes

Primary

Measure	Time frame	Description
Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	4 weeks postdose 3 (Month 7)	Serum antibodies to HPV types 6, 11, 16, and 18 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	4 weeks postdose 3 (Month 7)	Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24; HPV Type 31: ≥10; HPV Type 33: ≥8; HPV Type 45: ≥8; HPV Type 52: ≥8; HPV Type 58: ≥8.
Percentage of Participants With One or More Adverse Events	Up to 15 days after any vaccination	The percentage of participants with one or more adverse events was assessed.
Percentage of Participants With Study Discontinuation Due to an Adverse Event	Up to Month 7	The percentage of participants discontinued from the study due to an adverse event was assessed.
GMTs to HPV Types 31/33/45/52/58	4 weeks postdose 3 (Month 7)	Serum antibodies to HPV types 31, 33, 45, 52, and 58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL.
Percentage of Participants With Maximum Temperature ≥37.8 °C	Up to 5 days after any vaccination	The percentage of participants with a maximum temperature ≥37.8 °C 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.
Percentage of Participants With One or More Serious Adverse Events	Up to 15 days after any vaccination	The percentage of participants with one or more serious 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.

Countries

Belgium, Germany, Netherlands

Participant flow

Recruitment details

A total of 502 participants were screened and 500 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	249
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	251
Total	500

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	0	6
Overall Study	Withdrawal by Subject	3	2

Baseline characteristics

Characteristic	V503	GARDASIL	Total
Age, Continuous	20.8 Years STANDARD_DEVIATION 2.7	21.3 Years STANDARD_DEVIATION 3	21.0 Years STANDARD_DEVIATION 2.8
Age, Customized <18 years old	37 Participants	38 Participants	75 Participants
Age, Customized >=18 years old	212 Participants	213 Participants	425 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	249 Participants	251 Participants	500 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	196 / 248	189 / 248
serious Total, serious adverse events	0 / 248	6 / 248

Outcome results

Primary

Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18

Serum antibodies to HPV types 6, 11, 16, and 18 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL.

Time frame: 4 weeks postdose 3 (Month 7)

Population: All randomized participants. The number contributing to each data point is participants who received all 3 vaccinations within acceptable day ranges, had Month 7 serology for the HPV type within acceptable day ranges, were seronegative 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 6/11/16/18	HPV Type 6	758.3 milli Merck U/mL
V503	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 11	681.7 milli Merck U/mL
V503	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 16	3924.1 milli Merck U/mL
V503	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 18	884.3 milli Merck U/mL
GARDASIL	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 18	790.9 milli Merck U/mL
GARDASIL	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 6	618.4 milli Merck U/mL
GARDASIL	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 16	3787.9 milli Merck U/mL
GARDASIL	Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18	HPV Type 11	769.1 milli Merck U/mL

Comparison: HPV Type 6p-value: <0.00195% CI: [1.04, 1.45]ANOVA

Comparison: HPV Type 11p-value: <0.00195% CI: [0.76, 1.04]ANOVA

Comparison: HPV Type 16p-value: <0.00195% CI: [0.89, 1.21]ANOVA

Comparison: HPV Type 18p-value: <0.00195% CI: [0.91, 1.37]ANOVA

Secondary

GMTs to HPV Types 31/33/45/52/58

Serum antibodies to HPV types 31, 33, 45, 52, and 58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL.

Time frame: 4 weeks postdose 3 (Month 7)

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
V503	GMTs to HPV Types 31/33/45/52/58	HPV Type 33	460.5 milli Merck U/mL
V503	GMTs to HPV Types 31/33/45/52/58	HPV Type 52	430.7 milli Merck U/mL
V503	GMTs to HPV Types 31/33/45/52/58	HPV Type 31	794.4 milli Merck U/mL
V503	GMTs to HPV Types 31/33/45/52/58	HPV Type 58	691.0 milli Merck U/mL
V503	GMTs to HPV Types 31/33/45/52/58	HPV Type 45	262.9 milli Merck U/mL
GARDASIL	GMTs to HPV Types 31/33/45/52/58	HPV Type 58	5.7 milli Merck U/mL
GARDASIL	GMTs to HPV Types 31/33/45/52/58	HPV Type 33	3.4 milli Merck U/mL
GARDASIL	GMTs to HPV Types 31/33/45/52/58	HPV Type 45	2.5 milli Merck U/mL
GARDASIL	GMTs to HPV Types 31/33/45/52/58	HPV Type 52	1.9 milli Merck U/mL
GARDASIL	GMTs to HPV Types 31/33/45/52/58	HPV Type 31	14.8 milli Merck U/mL

Secondary

Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58

Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24; HPV Type 31: ≥10; HPV Type 33: ≥8; HPV Type 45: ≥8; HPV Type 52: ≥8; HPV Type 58: ≥8.

Time frame: 4 weeks postdose 3 (Month 7)

Arm	Measure	Group	Value (NUMBER)
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 11	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 33	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 18	99.6 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 45	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 16	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 52	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 31	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 58	100 Percentage of participants
V503	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 6	98.2 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 58	36.1 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 6	98.7 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 11	100 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 16	100 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 18	99.6 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 31	61.6 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 33	16.9 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 45	9.3 Percentage of participants
GARDASIL	Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58	HPV Type 52	2.5 Percentage of participants

Secondary