Clinical trial NCT00943722: A Study of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (V503-002)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Cancers
Vulvar Cancer
Vaginal Cancer
Genital Lesions
PAP Test Abnormalities
HPV Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-07-22
Enrollment: 3074
Sex: ALL
Minimum age (years): 9
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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. 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.

Detailed description: The base study V503-002 was a 12-month study that collected immunogenicity data through Month 7 and safety data through Month 12.

An optional extension study (V503-002 EXT1) collected safety and immunogenicity information through Month 36. Participants enrolled in the 16- to 26-year-old cohort in the base study were not included in EXT1. Per protocol, EXT1 included immunogenicity data from a subset of 9- to 15-year-old females and safety data from all 9- to 15-year-old females regardless of lot administered.

An optional second extension study (V503-002 EXT2) collected long-term safety and immunogenicity information through approximately Month 126. No study vaccine was administered in the extension studies. Participants enrolled in the 16- to 26-year-old cohort in the base study were not included in EXT2. Per protocol, EXT2 included immunogenicity data from a subset of 9- to 15-year-old females and effectiveness and safety data from all 9- to 15-year-old females regardless of lot administered.

Eligibility 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

Primary outcomes:
measure: 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])
timeFrame: 4 weeks post-vaccination 3 (Month 7)
measure: 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])
timeFrame: 4 weeks post-vaccination 3 (Month 7)
measure: Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
timeFrame: 4 weeks post-vaccination 3 (Month 7)
measure: Base Study: Percentage of Participants With Injection Site Adverse Experiences (AEs)
timeFrame: Up to 5 days after any vaccination
measure: Base Study: Percentage of Participants With Systemic AEs
timeFrame: Up to 15 days after any vaccination
measure: Base Study: Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC)
timeFrame: Up to 5 days after any vaccination
measure: Extension Study: GMTs For Each of the HPV Types Contained in the Vaccine
timeFrame: Up to ~Month 126
measure: Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine
timeFrame: Up to ~Month 126
Secondary outcomes:
measure: 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])
timeFrame: 4 weeks post-vaccination 3 (Month 7)
measure: 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])
timeFrame: 4 weeks post-vaccination 3 (Month 7)
measure: Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
timeFrame: 4 weeks post-vaccination 3 (Month 7)
measure: Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females
timeFrame: Up to ~Month 126
measure: Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males
timeFrame: Up to ~Month 126
measure: Extension Study: Combined Incidence of Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Genital Warts, and Cervical/Vulvar/Vaginal Cancers Related to HPV 6/11/16/18/31/33/45/52/58 in Females
timeFrame: Up to ~Month 126
measure: Extension Study: Combined Incidence of Penile Intraepithelial Neoplasia, Penile/Perineal/Perianal Cancers and Genital Warts Related to HPV 6/11/16/18/31/33/45/52/58 in Males
timeFrame: Up to ~Month 126
measure: Extension Study: Percentage of Participants With Vaccine-Related or Procedure-Related Serious Adverse Events
timeFrame: Up to ~Month 126
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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