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.
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.
Brief Title
A Study of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (V503-002)
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Cervical Cancers
Vulvar Cancer
Vaginal Cancer
Genital Lesions
PAP Test Abnormalities
HPV Infections
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
26 Years
Minimum Age
9 Years
NCT Id
NCT00943722
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
V503-002
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
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.
Outcome 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])
Outcome Time Frame
4 weeks post-vaccination 3 (Month 7)
Outcome Description
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.
Outcome 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])
Outcome Time Frame
4 weeks post-vaccination 3 (Month 7)
Outcome Description
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.
Outcome Measure
Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
Outcome Time Frame
4 weeks post-vaccination 3 (Month 7)
Outcome Description
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.
Outcome Measure
Base Study: Percentage of Participants With Injection Site Adverse Experiences (AEs)
Outcome Time Frame
Up to 5 days after any vaccination
Outcome Description
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.
Outcome Measure
Base Study: Percentage of Participants With Systemic AEs
Outcome Time Frame
Up to 15 days after any vaccination
Outcome Description
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.
Outcome Measure
Base Study: Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC)
Outcome Time Frame
Up to 5 days after any vaccination
Outcome Description
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.
Outcome Measure
Extension Study: GMTs For Each of the HPV Types Contained in the Vaccine
Outcome Time Frame
Up to ~Month 126
Outcome Description
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.
Outcome Measure
Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine
Outcome Time Frame
Up to ~Month 126
Secondary Ids
Secondary Id
2009_611
Secondary Id
2009-011617-25
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
4 weeks post-vaccination 3 (Month 7)
Outcome 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])
Outcome Description
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.
Outcome Time Frame
4 weeks post-vaccination 3 (Month 7)
Outcome 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])
Outcome Description
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.
Outcome Time Frame
4 weeks post-vaccination 3 (Month 7)
Outcome Measure
Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
Outcome Description
Persistent infection is when a participant is positive by polymerase chain reaction (PCR) for the same HPV type in cervicovaginal/external genital swabs or tissue specimens collected at consecutive visits at least 6 months (+/-1 month visit window) apart. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was from beginning of long-term follow-up or when a study participant reached 16 years of age, whichever came later. Per protocol, the extension study included 9- to 15-year-old females regardless of lot administered.
Outcome Time Frame
Up to ~Month 126
Outcome Measure
Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females
Outcome Description
Persistent infection is when a participant is positive by PCR for the same HPV type in external genital swabs or tissue specimens collected at consecutive visits at least 6 months (+/-1 month visit window) apart. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was from beginning of long-term follow-up or when a study participant reached 16 years of age, whichever came later.
Outcome Time Frame
Up to ~Month 126
Outcome Measure
Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males
Outcome Description
The 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 was assessed. This outcome measure was determined by clinical/pathologic criteria and positive PCR assay for HPV type. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was calculated starting from the beginning of the long-term follow-up study or the date when the study participant reached 16 years of age, whichever came later. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Outcome Time Frame
Up to ~Month 126
Outcome 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
Outcome Description
The combined incidence of penile intraepithelial neoplasia, penile/perineal/perianal cancers, and genital warts related to HPV6/11/16/18/31/33/45/52/58 was assessed. This outcome measure was determined by clinical/pathologic criteria and positive PCR assay for HPV type. Incidence was estimated as cases per 10,000 person-years. For each study participant, person-years follow up was calculated starting from the beginning of the long-term follow-up study or the date when the study participant reached 16 years of age, whichever came later.
Outcome Time Frame
Up to ~Month 126
Outcome 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
Outcome Description
A serious adverse event (SAE) included a death which resulted in the participant discontinuing the study, a serious adverse experience that was considered by an investigator who was a qualified physician to be possibly, probably, or definitely vaccine related or study procedure related. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Outcome Time Frame
Up to ~Month 126
Outcome Measure
Extension Study: Percentage of Participants With Vaccine-Related or Procedure-Related Serious Adverse Events
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
26
Minimum Age Number (converted to Years and rounded down)
9
Investigators
Investigator Type
Principal Investigator
Investigator Name
Margaret Aldrich
Investigator Email
maldrich@montefiore.org
Investigator Phone
Categories Mesh Debug
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gynecologic Cancers --- UTERINE CERVICAL DISEASES
Gynecologic Cancers --- UTERINE DISEASES
HIV/AIDS --- SEXUALLY TRANSMITTED DISEASES, VIRAL
Infectious Disease --- SEXUALLY TRANSMITTED DISEASES, VIRAL
HIV/AIDS --- SEXUALLY TRANSMITTED DISEASES
Infectious Disease --- SEXUALLY TRANSMITTED DISEASES
Hepatitis --- COMMUNICABLE DISEASES
HIV/AIDS --- COMMUNICABLE DISEASES
Infectious Disease --- COMMUNICABLE DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
MeSH Terms
UTERINE CERVICAL NEOPLASMS
VULVAR NEOPLASMS
VAGINAL NEOPLASMS
PAPILLOMAVIRUS INFECTIONS
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