Efficacy Against Oral Persistent Infection, Immunogenicity and Safety of the 9-valent Human Papillomavirus Vaccine (9vHPV) in Men Aged 20-45 Years (V503-049)

NCT04199689 | Active Not Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: V503-0492053462022-501974-21U1111-1275-86822019-003236-23
• Study Type: interventional
• Target: 6,033
• Locations: 16 countries
• Sites: 103

Brief Summary

The purpose of this study is to evaluate the efficacy, immunogenicity and safety of the 9vHPV vaccine in men 20 to 45 years of age. The primary hypothesis tested after the primary database lock is that administration of a 3-dose regimen of 9vHPV vaccine will reduce the incidence of human papillomavirus (HPV) 16/18/31/33/45/52/58-related oral persistent infection (6 months or longer) compared with placebo. There will also be an Extension Study to offer an opportunity to complete the 3 dose regimen of 9vHPV vaccine for participants who received placebo in the Base Study, or received less than 3 doses of 9vHPV vaccine in the Base Study.

Conditions

Papillomavirus Infections

Outcome Measures

Primary Outcomes (1)

• Incidence of HPV 16/18/31/33/45/52/58-related 6-month Persistent Oral Infection

  A 6-month persistent infection is defined to have occurred if a participant, after completion of the Month 7 visit, is positive for the same HPV type by the HPV polymerase chain reaction (PCR) assay to at least 1 common gene in Oral Rinse and Gargle (ORG) samples obtained at 2 or more consecutive visits at 6 months (+/-1 month visit window) apart.

  Up to Month 90

Secondary Outcomes (8)

• Incidence of HPV 6/11-related 6-month Persistent Oral Infection

  Up to Month 90

• Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies

  1 month postdose 3 (Month 7)

• Percentage of Participants who Seroconvert to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58

  1 month postdose 3 (Month 7)

• Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE)

  Up to 5 days after any vaccination

• Percentage of Participants with Elevated Temperature (Fever)

  Up to 5 days after any vaccination

Study Arms (2)

9vHPV vaccine

EXPERIMENTAL

Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6

Biological: 9vHPV Vaccine

Placebo

PLACEBO COMPARATOR

Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6

Other: Placebo (Saline for Injection)

Interventions

9vHPV Vaccine BIOLOGICAL

9vHPV is an aluminum-adjuvanted recombinant protein vaccine prepared from the highly purified virus-like particles of the recombinant major capsid (L1) protein of HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 given as a 0.5 mL intramuscular injection.

Also known as: GARDASIL®9, V503

9vHPV vaccine

Placebo (Saline for Injection) OTHER

0.9% sodium chloride given as a 0.5-mL intramuscular injection

Placebo

Eligibility Criteria

• Age: 20 Years - 45 Years
• Gender Eligibility Details: Healthy male participants between the ages of 20 and 45 years (inclusive)
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Base Study:
• Is healthy and is judged to be in good physical health based on medical history and physical examination
• Has provided written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research
• Agrees to provide study personnel with a primary telephone number as well as an alternate means of contact, if available (such as an alternate telephone number or email) for follow-up purposes
• Can read, understand, and complete the electronic vaccination report card (eVRC)
• Has had at least 1 lifetime sexual partner
• Extension Study:
• Provides documented consent for the Extension Study

You may not qualify if:

• Base Study:
• Has a history of HPV-related anal lesion (anal intraepithelial neoplasia or anal cancer) or HPV related head and neck cancer
• Has a history of or clinical evidence at the Day 1 external genital examination of HPV-related external lesion
• Has clinical evidence at the Day 1 external genital examination of gross genital lesion suggesting sexually transmitted disease
• Has a fever (defined as oral temperature ≥100.0°F or ≥37.8°C) within a 24-hour period prior to Day 1 visit
• Has a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention
• Is allergic to any vaccine component, including aluminum, yeast, or BENZONASE®
• Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections
• Is currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition
• Has a history of splenectomy
• Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate by judgment of investigator
• Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use
• Has received within 12 months prior to enrollment, is receiving, or plans to receive during the study, the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (ARAVA®), TNF-α antagonists, monoclonal antibody therapies (including rituximab \[RITUXAN®\]), intravenous immunoglobulin (IVIG), anti-lymphocyte sera, or other therapy known to interfere with the immune response. Regarding systemic corticosteroids, a participant will be excluded if he is currently receiving steroid therapy, has recently received such therapy, or has received 2 or more courses of high-dose corticosteroids (≥20 mg/day of prednisone \[or equivalent\] orally or parenterally) lasting at least 1 week in duration in the year prior. Participants using inhaled, nasal, or topical steroids are considered eligible for the study
• Has received within the 3 months prior to vaccination, is receiving, or plans to receive during the study, any immune globulin product (including RhoGAM™) or blood-derived product other than IVIG
• Has received inactivated or recombinant vaccines within 14 days prior to vaccination or receipt of live vaccines within 21 days prior to vaccination

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (103)

Valley Clinical Trials Inc. ( Site 0002)

Northridge, California, 91325, United States

Location

Inland Empire Clinical Trials, LLC ( Site 0025)

Rialto, California, 92377, United States

Location

Alta California Medical Group ( Site 0031)

Simi Valley, California, 93065, United States

Location

Encompass Clinical Research ( Site 0028)

Spring Valley, California, 91978, United States

Location

Diablo Clinical Research, Inc ( Site 0042)

Walnut Creek, California, 94598, United States

Location

Clinical Research of South Florida ( Site 0036)

Coral Gables, Florida, 33134, United States

Location

Acevedo Clinical Research Associates ( Site 0001)

Miami, Florida, 33142, United States

Location

Moffitt Cancer Center ( Site 0017)

Tampa, Florida, 33617, United States

Location

Augusta University ( Site 0010)

Augusta, Georgia, 30912, United States

Location

Solaris Clinical Research, LLC ( Site 0003)

Meridian, Idaho, 83646, United States

Location

Cotton-O'Neil Clinical Research Center ( Site 0044)

Topeka, Kansas, 66606, United States

Location

Heartland Research Associates, LLC ( Site 0034)

Wichita, Kansas, 67207, United States

Location

Kentucky Pediatric/Adult Research Inc ( Site 0011)

Bardstown, Kentucky, 40004, United States

Location

Healthcare Research Network LLC ( Site 0035)

Hazelwood, Missouri, 63042, United States

Location

Alliance for Multispecialty Reseach, LLC ( Site 0021)

Las Vegas, Nevada, 89119, United States

Location

Certified Research Associates ( Site 0041)

Cortland, New York, 13045, United States

Location

Laser Surgery Care ( Site 0018)

New York, New York, 10011, United States

Location

Weill Cornell Medicine ( Site 0046)

New York, New York, 10065, United States

Location

Rochester Clinical Research, Inc. ( Site 0008)

Rochester, New York, 14609, United States

Location

PMG Research of Salisbury ( Site 0009)

Salisbury, North Carolina, 28144, United States

Location

Rapid Medical Research, Inc. ( Site 0037)

Cleveland, Ohio, 44122, United States

Location

Preferred Primary Care Physicians ( Site 0032)

Pittsburgh, Pennsylvania, 15236, United States

Location

Coastal Carolina Research Center ( Site 0043)

North Charleston, South Carolina, 29405, United States

Location

Holston Medical Group ( Site 0030)

Kingsport, Tennessee, 37660, United States

Location

University of Texas Medical Branch at Galveston ( Site 0038)

Galveston, Texas, 77555-1115, United States

Location

Texas Center For Drug Development ( Site 0013)

Houston, Texas, 77081, United States

Location

Crossroads Clinical Research LLC ( Site 0027)

Victoria, Texas, 77901, United States

Location

J Lewis Research Inc/Foothill Family Clinic South ( Site 0006)

Salt Lake City, Utah, 84121, United States

Location

J Lewis Research Inc/Jordan River Family Medicine ( Site 0023)

South Jordan, Utah, 84095, United States

Location

Charlottesville Medical Research Center, LLC ( Site 0007)

Charlottesville, Virginia, 22911, United States

Location

Health Research of Hampton Roads, Inc. ( Site 0015)

Newport News, Virginia, 23606, United States

Location

Clinical Research Partners, LLC. ( Site 0004)

Richmond, Virginia, 23226, United States

Location

University of Antwerp ( Site 0352)

Wilrijk, Antwerpen, 2610, Belgium

Location

Universitair Ziekenhuis Gasthuisberg ( Site 0353)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Femicare VZW ( Site 0350)

Tienen, Vlaams-Brabant, 3300, Belgium

Location

Hospital Santo Antonio - Obras Sociais Irma Dulce ( Site 0101)

Salvador, Estado de Bahia, 40415-006, Brazil

Location

CPCLIN ( Site 0100)

Natal, Rio Grande do Norte, 59025-050, Brazil

Location

Centro de Pesquisa Clinica II - ICHC - FMUSP ( Site 0102)

São Paulo, 05402-000, Brazil

Location

Fundacion Centro de Investigacion Clinica CIC ( Site 0153)

Medellín, Antioquia, 050021, Colombia

Location

Clinica de la Costa Ltda. ( Site 0152)

Barranquilla, Atlántico, 080020, Colombia

Location

Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0156)

Chía, Cundinamarca, 250001, Colombia

Location

Centrum ambulantni gynekologie a primarni pece ( Site 0401)

Brno, Brno-mesto, 602 00, Czechia

Location

G-CENTRUM Olomouc s.r.o. ( Site 0400)

Olomouc, 772 00, Czechia

Location

MediStar s.r.o. ( Site 0403)

Prague, 120 00, Czechia

Location

FN Motol ( Site 0402)

Prague, 150 06, Czechia

Location

CHU Dijon Bourgogne - Hopital F. Mitterrand ( Site 0223)

Dijon, Cote-d Or, 21079, France

Location

Hopital Saint Eloi ( Site 0504)

Montpellier, Herault, 34295, France

Location

C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0507)

Rennes, Ille-et-Vilaine, 35033, France

Location

CHU Nantes - Hopital Hotel Dieu ( Site 0510)

Nantes, Loire-Atlantique, 44093, France

Location

Hopital Cochin ( Site 0506)

Paris, Île-de-France Region, 75014, France

Location

Infektiologikum Frankfurt-Sachsenhausen ( Site 0456)

Frankfurt am Main, Hesse, 60596, Germany

Location

Epimed GmbH ( Site 0450)

Berlin, 10787, Germany

Location

Klinische Forschung Berlin ( Site 0454)

Berlin, 10787, Germany

Location

Universitatsklinikum Hamburg-Eppendorf ( Site 0451)

Hamburg, 20246, Germany

Location

Meir Medical Center ( Site 0602)

Kfar Saba, Central District, 4428164, Israel

Location

Maccabi Health Services Medical Center ( Site 0604)

Tel Aviv, Central District, 6789140, Israel

Location

Rambam Medical Center ( Site 0601)

Haifa, 3525408, Israel

Location

Hadassah Medical Center. Ein Kerem ( Site 0600)

Jerusalem, 9112001, Israel

Location

Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 0551)

Rome, Roma, 00144, Italy

Location

Azienda Ospedaliera - Universita di Padova ( Site 0555)

Padua, Veneto, 35128, Italy

Location

Azienda Ospedaliera Policlinico di Bari ( Site 0550)

Bari, 70124, Italy

Location

AOU Policlinico Vittorio Emanuele ( Site 0552)

Catania, 95123, Italy

Location

Universita di Roma "La Sapienza" ( Site 0553)

Roma, 00161, Italy

Location

P-One Clinic, Keikokai Medical Corp. ( Site 1101)

Hachiōji, Tokyo, 192-0071, Japan

Location

Sagiyama Urology Clinic ( Site 1116)

Fukuoka, 810-0001, Japan

Location

Souseikai PS Clinic ( Site 1103)

Fukuoka, 812-0025, Japan

Location

Souseikai Nishikumamoto Hospital ( Site 1104)

Kumamoto, 861-4157, Japan

Location

Medical Corporation Heishinkai OPHAC Hospital ( Site 1105)

Osaka, 532-0003, Japan

Location

Nomura Clinic Namba ( Site 1114)

Osaka, 542-0076, Japan

Location

Medical Corporation Seiwakai Hayakawa Clinic ( Site 1113)

Osaka, 542-0086, Japan

Location

Doujin Memorial Medical Foundation, Meiwa Hospital ( Site 1111)

Tokyo, 101-0041, Japan

Location

Taisei Clinic ( Site 1109)

Tokyo, 107-0052, Japan

Location

Medical Corporation Mori to Umi Tokyo Tokyo Kamata Hospital ( Site 1112)

Tokyo, 144-0051, Japan

Location

Naoko Dermatology Clinic ( Site 1107)

Tokyo, 158-0097, Japan

Location

Medical Corporation Shinanokai Shinanozaka Clinic ( Site 1106)

Tokyo, 160-0017, Japan

Location

Medical Corporation Iseikai My City Clinic ( Site 1108)

Tokyo, 160-0022, Japan

Location

Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 1102)

Tokyo, 171-0014, Japan

Location

Kusunoki Clinic ( Site 1110)

Tokyo, 175-0092, Japan

Location

Arke Estudios Clinicos S.A. de C.V. ( Site 0203)

Mexico City, Mexico City, 06700, Mexico

Location

Instituto Nacional de Salud Publica ( Site 0202)

Cuernavaca, Morelos, 62100, Mexico

Location

Icaro Investigaciones en Medicina S.A. de C.V. ( Site 0200)

Chihuahua City, 31000, Mexico

Location

ARKE Estudios Clinicos S.A de C.V ( Site 0211)

Veracruz, 91910, Mexico

Location

Asociacion Civil Selva Amazonica ( Site 0252)

Iquitos, Loreto, 16000, Peru

Location

Policlinico Universidad Nacional Mayor de San Marcos ( Site 0257)

Lima, 07006, Peru

Location

Investigaciones Medicas en Salud - INMENSA ( Site 0255)

Lima, 15046, Peru

Location

Instituto de Investigacion Nutricional - Anexo Huascar ( Site 0251)

Lima, 15423, Peru

Location

Asociacion Via Libre ( Site 0250)

Lima, LIMA 01, Peru

Location

Korea University Ansan Hospital ( Site 0952)

Ansan-si, Kyonggi-do, 15355, South Korea

Location

The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 0954)

Seoul, 03312, South Korea

Location

Severance Hospital ( Site 0953)

Seoul, 03722, South Korea

Location

Hallym University Kangnam Sacred Heart Hospital ( Site 0951)

Seoul, 07441, South Korea

Location

Korea University Guro Hospital ( Site 0950)

Seoul, 08308, South Korea

Location

Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0755)

Badalona, Barcelona, 08916, Spain

Location

CAP Centelles ( Site 0751)

Centelles, Barcelona, 08540, Spain

Location

ICO L Hospitalet ( Site 0754)

L'Hospitalet de Llobregat, Barcelona, 08090, Spain

Location

Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1003)

Kaohsiung City, 833, Taiwan

Location

National Cheng Kung University Hospital ( Site 1002)

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital ( Site 1000)

Taipei, 100, Taiwan

Location

Chang Gung Medical Foundation.Linkou Branch ( Site 1001)

Taoyuan District, 333, Taiwan

Location

Armed Forces Research Institute of Medical Sciences ( Site 1051)

Bangkok, Bangkok, 10400, Thailand

Location

Vaccine Trial Center Faculty of Tropical Medicine ( Site 1052)

Bangkok, Bangkok, 10400, Thailand

Location

Faculty of Medicine Siriraj Hospital ( Site 1050)

Bangkok, Bangkok, 10700, Thailand

Location

Research Institute for Health Sciences ( Site 1053)

Chiang Mai, 50200, Thailand

Location

Related Publications (4)

• 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.

  PMID: 41276263 DERIVED

• Giuliano AR. Initiation of three complementary international studies investigating prevalence of oral HPV infection, burden of HPV-related head and neck disease, and efficacy of 9-valent HPV vaccination against oral HPV persistent infection. Contemp Clin Trials. 2022 Apr;115:106629. doi: 10.1016/j.cct.2021.106629. Epub 2021 Nov 24. No abstract available.

  PMID: 34838718 DERIVED

• Morais E, Kothari S, Roberts C, Yen G, Chen YT, Lynam M, Pedros M, Mirghani H, Alemany L, Pavon MA, Waterboer T, Mehanna H, Giuliano AR. Oral human papillomavirus (HPV) and associated factors among healthy populations: The design of the PROGRESS (PRevalence of Oral hpv infection, a Global aSSessment) study. Contemp Clin Trials. 2022 Apr;115:106630. doi: 10.1016/j.cct.2021.106630. Epub 2021 Nov 25.

  PMID: 34838717 DERIVED

• Giuliano AR, Wilkin T, Bautista OM, Cheon K, Connor L, Dubey S; Thomas Group; Luxembourg A, Rawat S, Shaw A, Velicer C, Vendetti N, Tu Y. Design of a phase III efficacy, immunogenicity, and safety study of 9-valent human papillomavirus vaccine in prevention of oral persistent infection in men. Contemp Clin Trials. 2022 Apr;115:106592. doi: 10.1016/j.cct.2021.106592. Epub 2021 Oct 19.

  PMID: 34678491 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Papillomavirus Infections

Interventions

Sodium Chloride; Injections

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 16, 2019
• Study Start: February 27, 2020
• Primary Completion (Estimated): August 27, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

ME (4); ES (3); TW (4); TH (4); IL (4); US (32); DE (4); BE (3); CZ (4); CO (3); IT (5); PE (5); FR (5); KR (5); JP (15); BR (3)