Efficacy, Immunogenicity, and Safety Study of the 9vHPV Vaccine in Japanese Males (V503-064)
- Conditions
- Neoplasms, AnalWarts, Genital
- Interventions
- Other: Placebo
- Registration Number
- NCT04635423
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purposes of this phase 3, double-blind, placebo-controlled clinical study are to evaluate the efficacy of V503 (9-valent human papillomavirus \[9vHPV\] vaccine) in preventing human papillomavirus (HPV)-related anogenital persistent infection, and to evaluate the safety/tolerability of V503, in Japanese males who are 16 to 26 years of age. It is hypothesized that administration of a 3-dose regimen of V503 reduces the combined incidence of HPV 6/11/16/18-related anogenital persistent infection, as well as the combined incidence of HPV 31/33/45/52/58-related anogenital persistent infection, compared with placebo.
The study includes a Base Study to assess efficacy and safety of V503, and an Extension Study. Participants who received placebo in the Base Study will be eligible to receive V503 vaccine on Day 1, Month 2, and Month 6 of the Extension Study. Participants who received less than 3 doses of V503 in the Base Study will be offered the opportunity to complete the 3-dose regimen in the Extension Study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 1059
- Is a Japanese male 16 to 26 years of age
- Has no more than 5 lifetime sexual partners
- Has a history of known prior vaccination with an HPV vaccine or plans to receive one outside the study
- Has a history of external genital warts
- Has a history of severe allergic reaction that required medical intervention
- Has received immune globulin or blood-derived products in the past 3 months or plan to receive any before Month 7 of the study
- Has a history of splenectomy, is currently immunocompromised, or has been diagnosed with immunodeficiency, human immunodeficiency virus (HIV), lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition
- Has received immunosuppressive therapy in the past year, excluding inhaled, nasal, or topical corticosteroids and certain regimens of systemic corticosteroids
- Has a known thrombocytopenia or coagulation disorder that would contraindicate intramuscular injections
- Has ongoing alcohol or drug abuse within the past 12 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description V503 V503 Participants receive an intramuscular (IM) injection of V503 (9-valent human papillomavirus \[9vHPV\] vaccine) at Day 1, Month 2, and Month 6. Placebo Placebo Participants receive an IM injection of placebo at Day 1, Month 2, and Month 6. V503 V503 Participants receive an intramuscular (IM) injection of V503 at Day 1, Month 2, and Month 6. Placebo Placebo Participants receive an IM injection of placebo at Day 1, Month 2, and Month 6.
- Primary Outcome Measures
Name Time Method Percentage of Participants With ≥1 Serious Adverse Events (SAEs) Up to approximately 37 months An SAE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention, that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, results in persistent/significant disability/incapacity, is a congenital birth defect, or is another important medical event. The percentage of participants who experienced at least 1 SAE is reported here for all randomized participants in the All Participants as Treated (APaT) population.
Number of Participants With Elevated Oral Body Temperature Up to 5 days after any vaccination 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 using the vaccination report card (VRC). Per protocol, fever was defined as an oral temperature of ≥99.5°F(37.5°C). The number of participants who had at least 1 oral body temperature reading that was, \<99.5°F (\<37.5ºC), ≥99.5°F (≥37.5ºC) and \<100.4°F (38.0°C), or ≥100.4°F (38.0°C) and \<101.3°F(38.5°C), or ≥101.3°F(38.5°C) is reported here for all randomized participants in the APaT population with temperature data available.
Combined Incidence of Human Papillomavirus (HPV) 6/11/16/18-related Anogenital Persistent Infection Up to approximately 36 Months Combined incidence of HPV type(s) 6/11/16/18-related anogenital persistent infection was defined to have occurred in a participant; 1) who is polymerase chain reaction (PCR) positive to at least one applicable HPV type(s) in 2 consecutive anogenital or biopsy samples from at least 2 consecutive visits 6 months (±1 month visit) or longer apart, or 2) who has a pathology diagnosis of condyloma, penile/perineal/perianal intraepithelial neoplasia, or penile, perineal or perianal cancer and PCR detection of at least one applicable HPV type(s) in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit with regardless of visit interval, prior to or following the biopsy showing HPV disease. Incidence was defined as the number of cases per 100 person-years of follow-up in both V503 and placebo arms. Per protocol, cases per 100 person-years is reported for applicable HPV type eligible participants with data available in the per-protocol efficacy population (PPE).
Percentage of Participants With Solicited Injection-site Adverse Events (AEs) Up to 5 days after any vaccination An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, tenderness/pain, and swelling) is reported here for all randomized participants in the All Participants as Treated (APaT) population.
Percentage of Participants With ≥1 Systemic AE Up to 15 days after any vaccination An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least 1 systemic AE is reported here for all randomized participants in the All Participants as Treated (APaT) population.
- Secondary Outcome Measures
Name Time Method Combined Incidence of HPV 31/33/45/52/58-related Anogenital Persistent Infection Up to approximately 36 Months Combined incidence of HPV type(s) 31/33/45/52/58-related anogenital persistent infection was defined to have occurred in a participant; 1) who is polymerase chain reaction (PCR) positive to at least 1 applicable HPV type(s) in 2 consecutive anogenital or biopsy samples from at least 2 consecutive visits 6 months (±1 month visit) or longer apart, or 2) who has a pathology diagnosis of condyloma, penile/perineal/perianal intraepithelial neoplasia, or penile, perineal or perianal cancer and PCR detection of at least 1 applicable HPV type in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit with regardless of visit interval, prior to or following the biopsy showing HPV disease. Incidence was defined as the number of cases per 100 person-years of follow-up in both V503 and placebo arms. Per protocol, cases per 100 person-years is reported for applicable HPV type(s) eligible participants with data available in the per-protocol efficacy population (PPE).
Geometric Mean Titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58 - All Randomized Participants Month 7 Antibodies to the HPV types 6/11/16/18/31/33/45/52/58 contained in V503 were measured using a competitive Luminex immunoassay (cLIA). Per protocol, antibody titers were expressed as milli Merck units/milliliter (mMU/mL). Geometric Mean Titers (GMTs) is reported for both V503 and Placebo for all randomized participants of the per-protocol immunogenicity population (PPI).
Geometric Mean Titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup Month 7 Antibodies to the HPV types 6/11/16/18/31/33/45/52/58 contained in V503 were measured using a competitive Luminex immunoassay (cLIA). Per protocol, antibody titers were expressed as milli Merck units/milliliter (mMU/mL). Geometric Mean Titers (GMTs) is reported for both V503 and Placebo for the heterosexual males (HM) subgroup of the per-protocol immunogenicity population (PPI).
Geometric Mean Titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex With Males (MSM) Participant Subgroup Month 7 Antibodies to the HPV types 6/11/16/18/31/33/45/52/58 contained in V503 were measured using a competitive Luminex immunoassay (cLIA). Per protocol, antibody titers were expressed as milli Merck units/milliliter (mMU/mL). Geometric Mean Titers (GMTs) is reported for both V503 and Placebo for the males who have sex with males (MSM) subgroup of the per-protocol immunogenicity population (PPI).
Percentage of Participants With Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - All Randomized Participants Month 7 Percentage of seroconversion to each of HPV 6/11/16/18/31/33/45/52/58 at Month 7 based on competitive Luminex immunoassay (cLIA) from participant serum samples. Seroconversion is defined as changing a participant's serostatus from seronegative at Day 1 to seropositive at 1 month post last dose Month 7. A participant with anti-HPV cLIA titer at or above the serostatus cutoff values of the cLIA for a given HPV type is considered seropositive for that HPV type. The serostatus cutoffs (milli Merck units/milliliter (mMU/mL)) for HPV types were as follows: HPV Type 6: ≥65, HPV Type 11: ≥37; HPV Type 16: ≥79, HPV Type 18: ≥85, HPV Type 31: ≥46, HPV Type 33: ≥26, HPV Type 45: ≥21, HPV Type 52: ≥30, and HPV Type 58: ≥31. The percentage of participants with seroconversion is reported for both V503 and Placebo for all randomized participants of the per-protocol immunogenicity population (PPI).
Percentage of Participants With Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup Month 7 Percentage of seroconversion to each of HPV 6/11/16/18/31/33/45/52/58 at Month 7 based on competitive Luminex immunoassay (cLIA) from participant serum samples. Seroconversion is defined as changing a participant's serostatus from seronegative at Day 1 to seropositive at 1 month post last dose Month 7. A participant with anti-HPV cLIA titer at or above the serostatus cutoff values of the cLIA for a given HPV type is considered seropositive for that HPV type. The serostatus cutoffs (milli Merck units/milliliter (mMU/mL)) for HPV types were as follows: HPV Type 6: ≥65, HPV Type 11: ≥37; HPV Type 16: ≥79, HPV Type 18: ≥85, HPV Type 31: ≥46, HPV Type 33: ≥26, HPV Type 45: ≥21, HPV Type 52: ≥30, and HPV Type 58: ≥31. The percentage of participants with seroconversion is reported for both V503 and Placebo for the heterosexual males (HM) subgroup of the per-protocol immunogenicity population (PPI).
Percentage of Participants With Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex With Males (MSM) Participant Subgroup Month 7 Percentage of seroconversion to each of HPV 6/11/16/18/31/33/45/52/58 at Month 7 based on competitive Luminex immunoassay (cLIA) from participant serum samples. Seroconversion is defined as changing a participant's serostatus from seronegative at Day 1 to seropositive at 1 month post last dose Month 7. A participant with anti-HPV cLIA titer at or above the serostatus cutoff values of the cLIA for a given HPV type is considered seropositive for that HPV type. The serostatus cutoffs (milli Merck units/milliliter (mMU/mL)) for HPV types were as follows: HPV Type 6: ≥65, HPV Type 11: ≥37; HPV Type 16: ≥79, HPV Type 18: ≥85, HPV Type 31: ≥46, HPV Type 33: ≥26, HPV Type 45: ≥21, HPV Type 52: ≥30, and HPV Type 58: ≥31. The percentage of participants with seroconversion is reported for both V503 and Placebo for the males who have sex with males (MSM) subgroup of the per-protocol immunogenicity population (PPI).
Trial Locations
- Locations (22)
Kanno Clinic ( Site 6402)
🇯🇵Sakai, Osaka, Japan
Seiyukai Medical Corporation Itoh Skin Clinic ( Site 6416)
🇯🇵Tokyo, Japan
P-One Clinic, Keikokai Medical Corp. ( Site 6419)
🇯🇵Hachioji, Tokyo, Japan
Doujin Memorial Medical Foundation, Meiwa Hospital ( Site 6404)
🇯🇵Tokyo, Japan
Yuge Clinic ( Site 6421)
🇯🇵Tokyo, Japan
Taisei Clinic ( Site 6403)
🇯🇵Tokyo, Japan
Mildix Skin Clinic ( Site 6423)
🇯🇵Tokyo, Japan
Medical Corporation Seiwakai Hayakawa Clinic ( Site 6409)
🇯🇵Osaka, Japan
Yamanaka Clinic ( Site 6410)
🇯🇵Osaka, Japan
Sugisawa Dermatology Clinic ( Site 6422)
🇯🇵Tokyo, Japan
Medical Corporation Sanshikai Toru Clinic ( Site 6401)
🇯🇵Tokyo, Japan
Naoko Dermatology Clinic ( Site 6417)
🇯🇵Tokyo, Japan
Ogikuboekimae Clinic ( Site 6413)
🇯🇵Tokyo, Japan
Medical Corporation Mori to Umi Tokyo Tokyo Kamata Hospital ( Site 6418)
🇯🇵Tokyo, Japan
Kusunoki Clinic ( Site 6412)
🇯🇵Tokyo, Japan
Medical Corporation Iseikai My City Clinic ( Site 6414)
🇯🇵Tokyo, Japan
Shinjuku Higashiguchi Clinic ( Site 6415)
🇯🇵Tokyo, Japan
Ocean Clinic ( Site 6407)
🇯🇵Yokohama, Kanagawa, Japan
Umeyama Clinic ( Site 6406)
🇯🇵Takasaki, Gunma, Japan
Iwasa Clinic ( Site 6411)
🇯🇵Osaka, Japan
Nomura Clinic Namba ( Site 6405)
🇯🇵Osaka, Japan
Association of Healthcare Corporation Koukankai Koukan Clinic ( Site 6424)
🇯🇵Kawasaki, Kanagawa, Japan