Efficacy, Immunogenicity, and Safety Study of V503 (9-valent Human Papillomavirus [9vHPV] Vaccine) in Japanese Males (V503-064)

Merck Sharp & Dohme LLC1,059 enrolled

Overview

The purposes of this phase 3, double-blind, placebo-controlled clinical study are to evaluate the efficacy of V503 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

1,059

Conditions

Warts, Genital Neoplasms, Anal

Interventions

V503BIOLOGICAL

9-valent vaccine, HPV 6/11/16/18/31/33/45/52/58, L1 virus-like particle (VLP) 30/40/60/40/20/20/20/20/20 mcg per dose.

PlaceboOTHER

0.9% sodium chloride (NaCL)

Eligibility

Sex: MALEMin age: 16 YearsMax age: 26 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Is a Japanese male 16 to 26 years of age * Has no more than 5 lifetime sexual partners Exclusion Criteria: * 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

Locations (22)

Umeyama Clinic ( Site 6406)

Takasaki, Gunma, Japan

Association of Healthcare Corporation Koukankai Koukan Clinic ( Site 6424)

Kawasaki, Kanagawa, Japan

Ocean Clinic ( Site 6407)

Yokohama, Kanagawa, Japan

Kanno Clinic ( Site 6402)

Sakai, Osaka, Japan

P-One Clinic, Keikokai Medical Corp. ( Site 6419)

Hachiōji, Tokyo, Japan

Iwasa Clinic ( Site 6411)

Osaka, Japan

Nomura Clinic Namba ( Site 6405)

Osaka, Japan

Medical Corporation Seiwakai Hayakawa Clinic ( Site 6409)

Osaka, Japan

Yamanaka Clinic ( Site 6410)

Osaka, Japan

Doujin Memorial Medical Foundation, Meiwa Hospital ( Site 6404)

Tokyo, Japan

...and 12 more locations

Outcomes

Primary Outcomes

Base Study: Combined Incidence of Human Papillomavirus (HPV) 6/11/16/18-related Anogenital Persistent Infection

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).

Time frame: Up to approximately 36 Months

Base Study: Percentage of Participants With Solicited Injection-site Adverse Events (AEs)

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.

Time frame: Up to 5 days after any vaccination

Base Study: Percentage of Participants With ≥1 Systemic AE

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.

Time frame: Up to 15 days after any vaccination

Base Study: Percentage of Participants With ≥1 Serious Adverse Events (SAEs)

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.

Time frame: Up to approximately 37 months

Base Study: Number of Participants With Elevated Oral Body Temperature

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.

Time frame: Up to 5 days after any vaccination

Secondary Outcomes

Base Study: Combined Incidence of HPV 31/33/45/52/58-related Anogenital Persistent Infection

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).

Time frame: Up to approximately 36 Months

Base Study: Geometric Mean Titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58 - All Randomized Participants

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).

Time frame: Month 7

Base Study: Geometric Mean Titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup

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).

Time frame: Month 7

Base Study: Geometric Mean Titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex With Males (MSM) Participant Subgroup

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).

Data from ClinicalTrials.gov

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Base Study: Percentage of Participants With Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - All Randomized Participants

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).

Time frame: Month 7

Base Study: Percentage of Participants With Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup

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).

Time frame: Month 7

Base Study: 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

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).

Time frame: Month 7