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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00943722
First received: July 21, 2009
Last updated: August 4, 2015
Last verified: August 2015
  Purpose

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. 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. 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. 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. 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.

Condition Intervention Phase
Cervical Cancers
Vulvar Cancer
Vaginal Cancer
Genital Lesions
PAP Test Abnormalities
HPV Infections
Biological: V503
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase III Clinical Trial to Study the Immunogenicity, Tolerability, and Manufacturing Consistency of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (9 to 15 Year Olds) With a Comparison to Young Women (16 to 26 Year Olds)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] Versus 16- to 26-Year-Old Females [Lot 1]) [ Time Frame: 4 weeks post-vaccination 3 (Month 7) ] [ Designated as safety issue: No ]
    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 are reported in milli Merck Units/mL.

  • GMTs for 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]) [ Time Frame: 4 weeks post-vaccination 3 (Month 7) ] [ Designated as safety issue: No ]
    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 are reported in milli Merck Units/mL.

  • GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study) [ Time Frame: 4 weeks post-vaccination 3 (Month 7) ] [ Designated as safety issue: No ]
    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 are reported in milli Merck Units/mL.

  • Percentage of Participants With Injection Site Adverse Experiences (AEs) [ Time Frame: up to 5 days after any vaccination ] [ Designated as safety issue: Yes ]
    An AE is 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 is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.

  • Percentage of Participants With Systemic AEs [ Time Frame: up to 15 days after any vaccination ] [ Designated as safety issue: Yes ]
    An AE is 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 is also an AE. Systemic AEs were those not categorized as injection-site AEs.

  • Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC) [ Time Frame: up to 5 days after any vaccination ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] Versus 16- to 26-Year-Old Females [Lot 1]) [ Time Frame: 4 weeks post-vaccination 3 (Month 7) ] [ Designated as safety issue: No ]
    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 cLIA. 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, and HPV Type 58: ≥8.

  • 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]) [ Time Frame: 4 weeks post-vaccination 3 (Month 7) ] [ Designated as safety issue: No ]
    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. 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, and HPV Type 58: ≥8.

  • Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study) [ Time Frame: 4 weeks post-vaccination 3 (Month 7) ] [ Designated as safety issue: No ]
    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 cLIA. 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, and HPV Type 58: ≥8.


Enrollment: 3074
Study Start Date: August 2009
Estimated Study Completion Date: December 2020
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 9- to 15-Year-Old Females (Lot 1)
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
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.
Experimental: 9- to 15-Year-Old Females (Lot 2)
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
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.
Experimental: 9- to 15-Year-Old Females (Lot 3)
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
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.
Experimental: 9- to 15-Year-Old Males (Lot 1)
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
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.
Experimental: 16- to 26-Year-Old Females (Lot 1)
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
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.

Detailed Description:

The base study V503-002 was a 12-month study that is collecting safety and immunogenicity information for six months following the subjects' third dose of study vaccine.

An optional extension study (V503-002 EXT1) will collect safety and immunogenicity information through Month 36. Participants enrolled in the 16- to 26-year-old cohort in the base study will not be included in EXT1.

An optional second extension study (V503-002 EXT2) will collect long-term safety and immunogenicity information through approximately 10 years. No study vaccine will be administered in the extension studies. Participants enrolled in the 16- to 26-year-old cohort in the base study will not be included in EXT2.

  Eligibility

Ages Eligible for Study:   9 Years to 26 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
  • Participant has a history of external genital lesions
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943722

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00943722     History of Changes
Other Study ID Numbers: V503-002, 2009_611
Study First Received: July 21, 2009
Results First Received: December 12, 2014
Last Updated: August 4, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Vaginal Neoplasms
Vulvar Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Vaginal Diseases
Vulvar Diseases

ClinicalTrials.gov processed this record on September 03, 2015