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

A Phase 3, Randomized, Placebo-controlled Clinical Study to Evaluate the Efficacy, Immunogenicity and Safety of the 9vHPV Vaccine in Japanese Males, 16 to 26 Years of Age.

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 Overview

• Status: Completed
• Conditions: Warts, Genital; Neoplasms, Anal
• Intervention / Treatment: Biological: V503; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1059
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 542-0073
    • Iwasa Clinic ( Site 6411)
  • Osaka, Japan, 542-0076
    • Nomura Clinic Namba ( Site 6405)
  • Osaka, Japan, 542-0086
    • Medical Corporation Seiwakai Hayakawa Clinic ( Site 6409)
  • Osaka, Japan, 553-0001
    • Yamanaka Clinic ( Site 6410)
  • Tokyo, Japan, 101-0041
    • Doujin Memorial Medical Foundation, Meiwa Hospital ( Site 6404)
  • Tokyo, Japan, 103-0014
    • Yuge Clinic ( Site 6421)
  • Tokyo, Japan, 107-0052
    • Taisei Clinic ( Site 6403)
  • Tokyo, Japan, 120-0034
    • Mildix Skin Clinic ( Site 6423)
  • Tokyo, Japan, 125-0041
    • Sugisawa Dermatology Clinic ( Site 6422)
  • Tokyo, Japan, 132-0011
    • Medical Corporation Sanshikai Toru Clinic ( Site 6401)
  • Tokyo, Japan, 144-0051
    • Medical Corporation Mori to Umi Tokyo Tokyo Kamata Hospital ( Site 6418)
  • Tokyo, Japan, 154-0024
    • Seiyukai Medical Corporation Itoh Skin Clinic ( Site 6416)
  • Tokyo, Japan, 158-0097
    • Naoko Dermatology Clinic ( Site 6417)
  • Tokyo, Japan, 160-0022
    • Medical Corporation Iseikai My City Clinic ( Site 6414)
  • Tokyo, Japan, 160-0022
    • Shinjuku Higashiguchi Clinic ( Site 6415)
  • Tokyo, Japan, 167-0051
    • Ogikuboekimae Clinic ( Site 6413)
  • Tokyo, Japan, 175-0092
    • Kusunoki Clinic ( Site 6412)
  • Gunma
    • Takasaki, Gunma, Japan, 370-0826
      • Umeyama Clinic ( Site 6406)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 210-0852
      • Association of Healthcare Corporation Koukankai Koukan Clinic ( Site 6424)
    • Yokohama, Kanagawa, Japan, 231-8331
      • Ocean Clinic ( Site 6407)
  • Osaka
    • Sakai, Osaka, Japan, 590-0024
      • Kanno Clinic ( Site 6402)
  • Tokyo
    • Hachiōji, Tokyo, Japan, 192-0071
      • P-One Clinic, Keikokai Medical Corp. ( Site 6419)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V503; In the base study, participants receive an intramuscular (IM) injection of V503 at Day 1, Month 2, and Month 6.	Biological: V503; 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.; Other Names: 9vHPV vaccine; SILGARD®9; GARDASIL™9
Placebo Comparator: Placebo; In the base study, participants receive an IM injection of placebo at Day 1, Month 2, and Month 6.	Other: Placebo; 0.9% sodium chloride (NaCL)
Experimental: V503 → Open Label V503 Extension Study; Participants from V503 arm of the base study who do not complete the 3-dose series receive 1 or 2 doses of V503, on Day 1, or Day 1 and Month 4 of the open label extension study.	Biological: V503; 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.; Other Names: 9vHPV vaccine; SILGARD®9; GARDASIL™9
Experimental: Placebo → Open Label V503 Extension Study; Participants from the placebo arm of the base study receive 3 doses of V503 on Day 1, Month 2 and Month 6 of the open label extension study.	Biological: V503; 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.; Other Names: 9vHPV vaccine; SILGARD®9; GARDASIL™9

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	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.	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.	Up to 5 days after any vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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).	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).	Month 7
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).	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).	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).	Month 7

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): July 23, 2025

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Infections; Virus Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Skin Diseases; Skin Diseases, Infectious; Tumor Virus Infections; Skin Diseases, Viral; Anus Diseases; Papillomavirus Infections; Rectal Neoplasms; Warts; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Anus Neoplasms; Condylomata Acuminata; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: V503-064 (Other Identifier: MSD Protocol Number); jRCT2031200217 (Registry Identifier: jRCT); 2020-001047-67 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes