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

Vulvar Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00943722
• Other study ID #: V503-002
• Secondary ID: 2009_6112009-011
• Status: Completed
• Phase: Phase 3
• Start date: August 27, 2009
• Est. completion date: April 22, 2021

Study information

• Verified date: September 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3074
• Est. completion date: April 22, 2021
• Est. primary completion date: April 30, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Years to 26 Years

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancers
• Genital Lesions
• HPV Infections
• PAP Test Abnormalities
• Papillomavirus Infections
• Vaginal Cancer
• Vaginal Neoplasms
• Vulvar Cancer
• Vulvar Neoplasms

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

References & Publications (4)

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 part — View Citation

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. Safe — View Citation

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 — View Citation

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; — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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])	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.	4 weeks post-vaccination 3 (Month 7)
Secondary	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])	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.	4 weeks post-vaccination 3 (Month 7)
Secondary	Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)	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.	4 weeks post-vaccination 3 (Month 7)
Secondary	Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females	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.	Up to ~Month 126
Secondary	Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males	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.	Up to ~Month 126
Secondary	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	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.	Up to ~Month 126
Secondary	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	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.	Up to ~Month 126
Secondary	Extension Study: Percentage of Participants With Vaccine-Related or Procedure-Related Serious Adverse Events	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.	Up to ~Month 126