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)

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)

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).

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus Infection
• Intervention / Treatment: Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)

• Study Type: Interventional
• Enrollment (Actual): 1518
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Girls 9 to 14 Years V503 at Months 0 and 6; 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); V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Boys 9 to 14 Years V503 at Months 0 and 6; 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); V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Girls and Boys 9 to 14 Years V503 at Months 0 and 12; 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); V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Experimental: Girls 9 to 14 Years V503 at Months 0, 2, and 6; 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); V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection
Active Comparator: Young Women 16 to 26 Years V503 at Months 0, 2, and 6; 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); V503, a 9-valent HPV (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24	Antibodies to HPV VLP types were measured using a competitive Luminex immunoassay. This outcome measure assessed the long-term persistence of antibody response. Antibody titers were expressed as milli Merck units/mL (mMU/mL).	Month 24
Antibody Persistence: Percentage of Participants With Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24	Antibodies to HPV VLP types were measured using a competitive Luminex immunoassay. This outcome measure assessed the long-term persistence of antibody response. Seroconversion to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were defined as a titer >=41, 24, 34, 39, 24, 18, 12, 16, and 12 mMU/mL, respectively. These cutoffs differ from analyses performed on samples collected up to Month 13; the antibody persistence analysis employed a new version of the assay.	Month 24
Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36	Antibodies to HPV VLP types were measured using a competitive Luminex immunoassay. This outcome measure assessed the long-term persistence of antibody response. Antibody titers were expressed as milli Merck units/mL (mMU/mL).	Month 36
Antibody Persistence: Percentage of Participants With Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36	Antibodies to HPV VLP types were measured using a competitive Luminex immunoassay. This outcome measure assessed the long-term persistence of antibody response. Seroconversion to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were defined as a titer >=41, 24, 34, 39, 24, 18, 12, 16, and 12 mMU/mL, respectively. These cutoffs differ from analyses performed on samples collected up to Month 13; the antibody persistence analysis employed a new version of the assay.	Month 36

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Iversen OE, Miranda MJ, Ulied A, Soerdal T, Lazarus E, Chokephaibulkit K, Block SL, Skrivanek A, Nur Azurah AG, Fong SM, Dvorak V, Kim KH, Cestero RM, Berkovitch M, Ceyhan M, Ellison MC, Ritter MA, Yuan SS, DiNubile MJ, Saah AJ, Luxembourg A. Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women. JAMA. 2016 Dec 13;316(22):2411-2421. doi: 10.1001/jama.2016.17615.
• Bornstein J, Roux S, Kjeld Petersen L, Huang LM, Dobson SR, Pitisuttithum P, Diez-Domingo J, Schilling A, Ariffin H, Tytus R, Rupp R, Senders S, Engel E, Ferris D, Kim YJ, Tae Kim Y, Kurugol Z, Bautista O, Nolan KM, Sankaranarayanan S, Saah A, Luxembourg A. Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine. Pediatrics. 2021 Jan;147(1):e20194035. doi: 10.1542/peds.2019-4035. Epub 2020 Dec 22.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2013
• Primary Completion (Actual): June 19, 2015
• Study Completion (Actual): July 24, 2017

Study Registration Dates

• First Submitted: November 8, 2013
• First Submitted That Met QC Criteria: November 14, 2013
• First Posted (Estimate): November 15, 2013

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Tumor Virus Infections; Papillomavirus Infections
• Other Study ID Numbers: V503-010 (Other Identifier: Merck Protocol Number); 2013-001314-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf