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)

• ClinicalTrials.gov Identifier: NCT01984697
• Recruitment Status: Completed
• First Posted: November 15, 2013
• Results First Posted: April 26, 2016
• Last Update Posted: August 8, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Human Papillomavirus Infection	Biological: V503 (9-valent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1518 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: December 12, 2013
• Actual Primary Completion Date: June 19, 2015
• Actual Study Completion Date: July 24, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Geometric Mean Titers to Human Papillomavirus (HPV) Type 6 After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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).
2. Geometric Mean Titers to HPV Type 11 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 11 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
3. Geometric Mean Titers to HPV Type 16 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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. Geometric Mean Titers to HPV Type 18 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
5. Geometric Mean Titers to HPV Type 31 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 31 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
6. Geometric Mean Titers to HPV Type 33 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 33 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
7. Geometric Mean Titers to HPV Type 45 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 45 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
8. Geometric Mean Titers to HPV Type 52 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 52 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
9. Geometric Mean Titers to HPV Type 58 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   Antibodies to HPV VLP type 58 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).

Secondary Outcome Measures :

1. Percentage of Participants With Seroconversion to HPV Type 6 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
2. Percentage of Participants With Seroconversion to HPV Type 11 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
3. Percentage of Participants With Seroconversion to HPV Type 16 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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. Percentage of Participants With Seroconversion to HPV Type 18 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
5. Percentage of Participants With Seroconversion to HPV Type 31 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
6. Percentage of Participants With Seroconversion to HPV Type 33 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
7. Percentage of Participants With Seroconversion to HPV Type 45 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
8. Percentage of Participants With Seroconversion to HPV Type 52 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.
9. Percentage of Participants With Seroconversion to HPV Type 58 at Four Weeks After the Last Dose of V503 in the Planned Regimen [ Time Frame: 4 weeks after the last dose of V503 in the planned regimen (Month 7 or Month 13) ]
   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.

Other Outcome Measures:

1. Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24 [ Time Frame: 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).
2. Antibody Persistence: Percentage of Participants With Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24 [ Time Frame: 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.
3. Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36 [ Time Frame: 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).
4. Antibody Persistence: Percentage of Participants With Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36 [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). pii: e20194035. doi: 10.1542/peds.2019-4035. Epub 2020 Dec 22.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01984697
• Other Study ID Numbers: V503-010; 2013-001314-15 ( EudraCT Number ); V503-010 ( Other Identifier: Merck Protocol Number )
• First Posted: November 15, 2013
• Results First Posted: April 26, 2016
• Last Update Posted: August 8, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Papillomavirus Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections