A Study of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (V503-002)

NCT00943722 | Completed Phase 3 Results DMC

• 3 other identifiers: V503-0022009_6112009-011617-25
• Study Type: interventional
• Target: 3,074
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the immunogenicity and tolerability of V503 (a multivalent human papillomavirus \[HPV\] L1 virus-like particle \[VLP\] vaccine) in preadolescent and adolescent participants between 9 and 15 years old and demonstrate the consistency of the manufactured vaccine through assessment of 3 different final manufacturing process lots of V503. The primary hypotheses are as follows:

1. 1.The 9-valent HPV L1 VLP vaccine when administered to preadolescent and adolescent boys and girls 9 to 15 years of age and young women 16 to 26 years of age is generally well-tolerated.
2. 2.9-valent HPV L1 VLP vaccine induces non-inferior immune responses in preadolescent and adolescent girls 9 to 15 years of age who are seronegative at Day 1 to the relevant HPV type compared to young women 16 to 26 years of age who are seronegative at Day 1 and polymerase chain reaction (PCR)-negative Day 1 through Month 7 to the relevant HPV type, as measured by anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 geometric mean titers (GMTs) at 4 weeks post-dose 3.
3. 3.The 9-valent HPV L1 VLP vaccine induces non-inferior immune responses in preadolescent and adolescent boys 9 to 15 years of age who are seronegative at Day 1 to the relevant HPV type compared to young women 16 to 26 years of age who are seronegative at Day 1 and PCR-negative Day 1 through Month 7 to the relevant HPV type, as measured by anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 GMTs at 4 weeks post-dose 3.
4. 4.Three separate final manufacturing process (FMP) lots of the 9-valent HPV L1 VLP vaccine induce similar immune responses, as measured by anti-HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 GMTs at 4 weeks post-dose 3.

Conditions

Cervical Cancers; Vulvar Cancer; Vaginal Cancer; Genital Lesions; PAP Test Abnormalities; HPV Infections

Outcome Measures

Primary Outcomes (8)

• Base Study: Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])

  Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.

  4 weeks post-vaccination 3 (Month 7)

• Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] and 16- to 26-Year-Old Females [Lot 1])

  Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.

  4 weeks post-vaccination 3 (Month 7)

• Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)

  Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers were reported in milli Merck Units/mL.

  4 weeks post-vaccination 3 (Month 7)

• Base Study: Percentage of Participants With Injection Site Adverse Experiences (AEs)

  An AE was defined as any unfavorable 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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine was also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.

  Up to 5 days after any vaccination

• Base Study: Percentage of Participants With Systemic AEs

  An AE was defined as any unfavorable 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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine was also an AE. Systemic AEs were those not categorized as injection-site AEs.

  Up to 15 days after any vaccination

• Base Study: Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC)

  Participants collected their oral body temperature in the evening of their vaccination day and at the same time each day thereafter for 4 days. The maximum body temperature obtained within 5 days of any of the 3 vaccinations was recorded. The percentage of participants who had at least 1 oral body temperature reading that was ≥100.0°F (≥37.8ºC) was summarized.

  Up to 5 days after any vaccination

• Extension Study: GMTs For Each of the HPV Types Contained in the Vaccine

  Serum antibody titers (milli Merck Units/mL) measured by cLIA to each of the 9vHPV types were assessed. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.

  Up to ~Month 126

• Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine

  Serum antibody titers for HPV VLPs Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined and reported in milli Merck Units/mL. The percentage of participants seropositive to each HPV type was reported. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.

  Up to ~Month 126

Secondary Outcomes (8)

• Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])

  4 weeks post-vaccination 3 (Month 7)

• Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] Versus 16- to 26-Year-Old Females [Lot 1])

  4 weeks post-vaccination 3 (Month 7)

• Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)

  4 weeks post-vaccination 3 (Month 7)

• Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females

  Up to ~Month 126

• Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males

  Up to ~Month 126

Study Arms (5)

9- to 15-Year-Old Females (Lot 1)

EXPERIMENTAL

9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lot 1.

Biological: V503

9- to 15-Year-Old Females (Lot 2)

EXPERIMENTAL

9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lot 2.

Biological: V503

9- to 15-Year-Old Females (Lot 3)

EXPERIMENTAL

9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lot 3.

Biological: V503

9- to 15-Year-Old Males (Lot 1)

EXPERIMENTAL

9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lot 1.

Biological: V503

16- to 26-Year-Old Females (Lot 1)

EXPERIMENTAL

9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lot 1.

Biological: V503

Interventions

V503 BIOLOGICAL

Multivalent HPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.

16- to 26-Year-Old Females (Lot 1); 9- to 15-Year-Old Females (Lot 1); 9- to 15-Year-Old Females (Lot 2); 9- to 15-Year-Old Females (Lot 3); 9- to 15-Year-Old Males (Lot 1)

Eligibility Criteria

• Age: 9 Years - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Boys and Girls Age 9 to 15:
• Participant has not had sexual intercourse prior to the study and does not plan to become sexually active during the study period Day 1 to Month 7
• Women Age 16 to 26:
• Participant has never had Pap testing or has had only normal results
• Participant has had 0 to 4 sexual partners at the time of enrollment

You may not qualify if:

• Boys and Girls Age 9 to 15:
• History of allergic reaction that required medical intervention
• Currently enrolled in any other clinical study
• Participant is pregnant
• Participant is immunocompromised or has taken immunosuppressants in the last year
• Participant has received a marketed HPV vaccine or participated in an HPV vaccine clinical trial
• Participant has a history of positive test for HPV
• Women Age 16 to 26:
• History of allergic reaction that required medical intervention
• Currently enrolled in any other clinical study
• Participant is pregnant
• Participant is immunocompromised or has taken immunosuppressants in the last year
• Participant has received a marketed HPV vaccine or participated in an HPV vaccine clinical trial
• Participant has a history of positive test for HPV
• Participant has a history of abnormal cervical biopsy result

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (7)

• Luxembourg A, Moreira ED Jr, Samakoses R, Kim KH, Sun X, Maansson R, Moeller E, Christiano S, Chen J. Phase III, randomized controlled trial in girls 9-15 years old to evaluate lot consistency of a novel nine-valent human papillomavirus L1 virus-like particle vaccine. Hum Vaccin Immunother. 2015;11(6):1306-12. doi: 10.1080/21645515.2015.1009819.

  PMID: 26086587 RESULT

• Van Damme P, Olsson SE, Block S, Castellsague X, Gray GE, Herrera T, Huang LM, Kim DS, Pitisuttithum P, Chen J, Christiano S, Maansson R, Moeller E, Sun X, Vuocolo S, Luxembourg A. Immunogenicity and Safety of a 9-Valent HPV Vaccine. Pediatrics. 2015 Jul;136(1):e28-39. doi: 10.1542/peds.2014-3745.

  PMID: 26101366 RESULT

• Moreira ED Jr, Block SL, Ferris D, Giuliano AR, Iversen OE, Joura EA, Kosalaraksa P, Schilling A, Van Damme P, Bornstein J, Bosch FX, Pils S, Cuzick J, Garland SM, Huh W, Kjaer SK, Qi H, Hyatt D, Martin J, Moeller E, Ritter M, Baudin M, Luxembourg A. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Pediatrics. 2016 Aug;138(2):e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.

  PMID: 27422279 RESULT

• Olsson SE, Restrepo JA, Reina JC, Pitisuttithum P, Ulied A, Varman M, Van Damme P, Moreira ED Jr, Ferris D, Block S, Bautista O, Gallagher N, McCauley J, Luxembourg A. Long-term immunogenicity, effectiveness, and safety of nine-valent human papillomavirus vaccine in girls and boys 9 to 15 years of age: Interim analysis after 8 years of follow-up. Papillomavirus Res. 2020 Dec;10:100203. doi: 10.1016/j.pvr.2020.100203. Epub 2020 Jul 11.

  PMID: 32659510 RESULT

• Restrepo J, Herrera T, Samakoses R, Reina JC, Pitisuttithum P, Ulied A, Bekker LG, Moreira ED, Olsson SE, Block SL, Hammes LS, Laginha F, Ferenczy A, Kurman R, Ronnett BM, Stoler M, Bautista O, Gallagher NE, Salituro G, Ye M, Luxembourg A. Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety. Pediatrics. 2023 Oct 1;152(4):e2022060993. doi: 10.1542/peds.2022-060993.

  PMID: 37667847 DERIVED

• Garland SM, Pitisuttithum P, Ngan HYS, Cho CH, Lee CY, Chen CA, Yang YC, Chu TY, Twu NF, Samakoses R, Takeuchi Y, Cheung TH, Kim SC, Huang LM, Kim BG, Kim YT, Kim KH, Song YS, Lalwani S, Kang JH, Sakamoto M, Ryu HS, Bhatla N, Yoshikawa H, Ellison MC, Han SR, Moeller E, Murata S, Ritter M, Sawata M, Shields C, Walia A, Perez G, Luxembourg A. Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries. J Infect Dis. 2018 Jun 5;218(1):95-108. doi: 10.1093/infdis/jiy133.

  PMID: 29767739 DERIVED

• Ruiz-Sternberg AM, Moreira ED Jr, Restrepo JA, Lazcano-Ponce E, Cabello R, Silva A, Andrade R, Revollo F, Uscanga S, Victoria A, Guevara AM, Luna J, Plata M, Dominguez CN, Fedrizzi E, Suarez E, Reina JC, Ellison MC, Moeller E, Ritter M, Shields C, Cashat M, Perez G, Luxembourg A. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women. Papillomavirus Res. 2018 Jun;5:63-74. doi: 10.1016/j.pvr.2017.12.004. Epub 2017 Dec 19.

  PMID: 29269325 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Papillomavirus Infections

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vulvar Diseases; Vaginal Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2009
• First Posted: July 22, 2009
• Study Start: August 27, 2009
• Primary Completion: April 30, 2011
• Study Completion: April 22, 2021
• Last Updated: October 3, 2022
• Results First Posted: January 13, 2015

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share