A Phase III Study of a 2-dose Regimen of a Multivalent Human Papillomavirus (HPV) Vaccine (V503), Administered to 9 to 14 Year-olds and Compared to Young Women, 16 to 26 Years Old (V503-010)

Study Overview
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Brief Summary
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This was a 37-month safety and immunogenicity study conducted in boys and girls 9 to 14 years of age and in young women 16 to 26 years of age. From this study, the goal was to establish that the investigational 2-dose regimens (0, 6 months and 0, 12 months) studied in boys and girls 9 to 14 years of age are generally safe and immunogenic, with an antibody response that is not inferior to that observed in young women 16 to 26 years of age who received the standard 3-dose regimen of V503 (i.e., the population and dose regimen used to establish V503 efficacy).

Official Title
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A Phase III Clinical Trial to Study the Tolerability and Immunogenicity of a 2-dose Regimen of V503, a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine, Administered in Preadolescents and Adolescents (9 to 14 Year Olds) With a Comparison to Young Women (16 to 26 Year Olds)

Conditions
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Human Papillomavirus Infection

Intervention / Treatment
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* Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Participants: -Judged to be in good physical health on the basis of medical history, physical examination and laboratory results Boys and Girls 9 to 14 Years: -Must not have had coitarche and does not plan on becoming sexually active during the vaccination period Women 16 to 26 Years: Has never had a Papanicolaou (Pap) test or only had normal Pap test results A lifetime history of 0 to 4 male and/or female sexual partners Exclusion Criteria: All Participants: Known allergy to any vaccine component History of severe allergic reaction that required medical intervention Thrombocytopenia or any coagulation disorder Females only: participant is pregnant or expecting to donate eggs during day 1 through month 7 Currently immunocompromised, or been diagnosed with immunodeficiency Had a splenectomy Receiving or has received immunosuppressive therapies within the last year Received any immunoglobulin product or blood-derived product within 3 months Received a marketed HPV vaccine or has participated in an HPV vaccine clinical trial

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 26 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Girls 9 to 14 Years V503 at Months 0 and 6<br>Girls aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL intramuscular (IM) injection at Months 0 and 6. An additional dose of V503 0.5 mL IM was administered at Month 36. | Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)<br>* V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Boys 9 to 14 Years V503 at Months 0 and 6<br>Boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 6. An additional dose of V503 0.5 mL IM was administered at Month 36. | Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)<br>* V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Girls and Boys 9 to 14 Years V503 at Months 0 and 12<br>Girls and boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 12. An additional dose of V503 0.5 mL IM was administered at Month 36. | Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)<br>* V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Experimental: Girls 9 to 14 Years V503 at Months 0, 2, and 6<br>Girls aged 9 to 14 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6. An additional dose of V503 0.5 mL IM was administered at Month 36 for a subset of participants. | Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)<br>* V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|
| Active Comparator: Young Women 16 to 26 Years V503 at Months 0, 2, and 6<br>Young Women aged 16 to 26 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6. An additional dose of V503 0.5 mL IM was administered at Month 36 for a subset of participants. | Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)<br>* V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers to Human Papillomavirus (HPV) Type 6 After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV virus-like particles (VLP) type 6 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 11 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 11 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 16 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 16 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 18 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 31 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 31 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 33 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 33 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 45 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 45 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 52 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 52 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Geometric Mean Titers to HPV Type 58 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 58 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion to HPV Type 6 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 6 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 6 was defined as a titer >=30 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 11 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 11 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 11 was defined as a titer >=16 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 16 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 16 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 16 was defined as a titer >=20 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 18 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 18 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 18 was defined as a titer >=24 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 31 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 31 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 31 was defined as a titer >=10 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 33 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 33 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 33 was defined as a titer >=8 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 45 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 45 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 45 was defined as a titer >=8 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 52 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 52 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 52 was defined as a titer >=8 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) | 
| Percentage of Participants With Seroconversion to HPV Type 58 at Four Weeks After the Last Dose of V503 in the Planned Regimen | Antibodies to HPV VLP type 58 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 58 was defined as a titer >=8 mMU/mL. | 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) |