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

Papillomavirus Infections Clinical Trial

Official title:

A Phase 3, International, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy, Immunogenicity, and Safety of the 9vHPV Vaccine, a Multivalent L1 Virus-like Particle Vaccine, in the Prevention of Oral Persistent Infection With HPV Types 16, 18, 31, 33, 45, 52, or 58 in Adult Males, 20 to 45 Years of Age

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04199689
• Other study ID #: V503-049
• Secondary ID: V503-04920534620
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 27, 2020
• Est. completion date: September 21, 2026

Study information

• Verified date: February 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy, immunogenicity and safety of the 9-valent human papillomavirus (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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6033
• Est. completion date: September 21, 2026
• Est. primary completion date: September 21, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

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:

• Participants may continue in the Extension Study if Inclusion Criteria #1 and #4 are still met, and the participants was in either the placebo group in the Base Study or the vaccine group in the Base Study but did not complete the vaccination series.
• Provides documented consent for the Extension Study. Exclusion Criteria:

Base Study:

• Has a history of human papillomavirus (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-a 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
• Is concurrently enrolled in other clinical studies of investigational agents
• Has previously received a marketed HPV vaccine, or has participated in a clinical trial for any HPV vaccine (receiving either active agent or placebo)
• Has engaged in sexual activity 48 hours prior to vaccination. Sexual activity is defined as: penile penetrative vaginal intercourse with female partner; penile penetrative or receptive anal intercourse with male or female partner; or oral sex involving any contact between participant's mouth with a female partner's vagina, genital or anal area or male partner's penis or genital or anal area. This also includes any contact between participant's partner's mouth with participant's penis, genital or anal area.
• Is unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period when study visits would need to be scheduled.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Extension Study:

• Participants must be excluded from the Extension Study if Base Study Exclusion Criteria #4, 5, 7, 10, 15, or 18 are met.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Papillomavirus Infections
• Persistent Infection

Intervention

Biological:
• 9vHPV Vaccine
9-valent human papillomavirus vaccine (9vHPV) is an aluminum-adjuvanted recombinant protein vaccine prepared from the highly purified virus-like particles (VLPs) 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.

Other:
• Placebo (Saline for Injection)
0.9% sodium chloride given as a 0.5-mL intramuscular injection

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gasthuisberg ( Site 0353)	Leuven	Vlaams-Brabant
Belgium	Femicare VZW ( Site 0350)	Tienen	Vlaams-Brabant
Belgium	University of Antwerp ( Site 0352)	Wilrijk	Antwerpen
Brazil	CPCLIN ( Site 0100)	Natal	Rio Grande Do Norte
Brazil	Hospital Santo Antonio - Obras Sociais Irma Dulce ( Site 0101)	Salvador	Bahia
Brazil	Centro de Pesquisa Clinica II - ICHC - FMUSP ( Site 0102)	Sao Paulo
Colombia	Clinica de la Costa Ltda. ( Site 0152)	Barranquilla	Atlantico
Colombia	Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0156)	Chia	Cundinamarca
Colombia	Fundacion Centro de Investigacion Clinica CIC ( Site 0153)	Medellin	Antioquia
Czechia	Centrum ambulantni gynekologie a primarni pece ( Site 0401)	Brno	Brno-mesto
Czechia	G-CENTRUM Olomouc s.r.o. ( Site 0400)	Olomouc
Czechia	MediStar s.r.o. ( Site 0403)	Praha 2
Czechia	FN Motol ( Site 0402)	Praha 5
France	CHU Dijon Bourgogne - Hopital F. Mitterrand ( Site 0223)	Dijon	Cote-d Or
France	Hopital Saint Eloi ( Site 0504)	Montpellier	Herault
France	CHU Nantes - Hopital Hotel Dieu ( Site 0510)	Nantes	Loire-Atlantique
France	Hopital Cochin ( Site 0506)	Paris	Ile-de-France
France	C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0507)	Rennes	Ille-et-Vilaine
Germany	Epimed GmbH ( Site 0450)	Berlin
Germany	Klinische Forschung Berlin ( Site 0454)	Berlin
Germany	Infektiologikum Frankfurt-Sachsenhausen ( Site 0456)	Frankfurt am Main	Hessen
Germany	Universitatsklinikum Hamburg-Eppendorf ( Site 0451)	Hamburg
Israel	Rambam Medical Center ( Site 0601)	Haifa
Israel	Hadassah Medical Center. Ein Kerem ( Site 0600)	Jerusalem
Israel	Meir Medical Center ( Site 0602)	Kfar Saba	Central
Israel	Maccabi Health Services Medical Center ( Site 0604)	Tel Aviv	HaMerkaz
Italy	Azienda Ospedaliera Policlinico di Bari ( Site 0550)	Bari
Italy	AOU Policlinico Vittorio Emanuele ( Site 0552)	Catania
Italy	Azienda Ospedaliera - Universita di Padova ( Site 0555)	Padova	Veneto
Italy	Universita di Roma "La Sapienza" ( Site 0553)	Roma
Italy	Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 0551)	Rome	Roma
Japan	Sagiyama Urology Clinic ( Site 1116)	Fukuoka
Japan	Souseikai PS Clinic ( Site 1103)	Fukuoka
Japan	P-One Clinic, Keikokai Medical Corp. ( Site 1101)	Hachioji	Tokyo
Japan	Souseikai Nishikumamoto Hospital ( Site 1104)	Kumamoto
Japan	Medical Corporation Heishinkai OPHAC Hospital ( Site 1105)	Osaka
Japan	Medical Corporation Seiwakai Hayakawa Clinic ( Site 1113)	Osaka
Japan	Nomura Clinic Namba ( Site 1114)	Osaka
Japan	Doujin Memorial Medical Foundation, Meiwa Hospital ( Site 1111)	Tokyo
Japan	Kusunoki Clinic ( Site 1110)	Tokyo
Japan	Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 1102)	Tokyo
Japan	Medical Corporation Iseikai My City Clinic ( Site 1108)	Tokyo
Japan	Medical Corporation Mori to Umi Tokyo Tokyo Kamata Hospital ( Site 1112)	Tokyo
Japan	Medical Corporation Shinanokai Shinanozaka Clinic ( Site 1106)	Tokyo
Japan	Naoko Dermatology Clinic ( Site 1107)	Tokyo
Japan	Taisei Clinic ( Site 1109)	Tokyo
Korea, Republic of	Korea University Ansan Hospital ( Site 0952)	Ansan-si	Kyonggi-do
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital ( Site 0951)	Seoul
Korea, Republic of	Korea University Guro Hospital ( Site 0950)	Seoul
Korea, Republic of	Severance Hospital ( Site 0953)	Seoul
Korea, Republic of	The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 0954)	Seoul
Mexico	Arke Estudios Clinicos S.A. de C.V. ( Site 0203)	Cdmx
Mexico	Icaro Investigaciones en Medicina S.A. de C.V. ( Site 0200)	Chihuahua
Mexico	Instituto Nacional de Salud Publica ( Site 0202)	Cuernavaca	Morelos
Mexico	ARKE Estudios Clinicos S.A de C.V ( Site 0211)	Veracruz
Peru	Asociacion Civil Selva Amazonica ( Site 0252)	Iquitos	Loreto
Peru	Asociacion Via Libre ( Site 0250)	Lima
Peru	Instituto de Investigacion Nutricional - Anexo Huascar ( Site 0251)	Lima
Peru	Investigaciones Medicas en Salud - INMENSA ( Site 0255)	Lima
Peru	Policlinico Universidad Nacional Mayor de San Marcos ( Site 0257)	Lima
Spain	Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0755)	Badalona	Barcelona
Spain	CAP Centelles ( Site 0751)	Centelles	Barcelona
Spain	ICO L Hospitalet ( Site 0754)	L Hospitalet De Llobregat	Barcelona
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1003)	Kaohsiung
Taiwan	National Cheng Kung University Hospital ( Site 1002)	Tainan
Taiwan	National Taiwan University Hospital ( Site 1000)	Taipei
Taiwan	Chang Gung Medical Foundation.Linkou Branch ( Site 1001)	Taoyuan
Thailand	Armed Forces Research Institute of Medical Sciences ( Site 1051)	Bangkok	Krung Thep Maha Nakhon
Thailand	Faculty of Medicine Siriraj Hospital ( Site 1050)	Bangkok	Krung Thep Maha Nakhon
Thailand	Vaccine Trial Center Faculty of Tropical Medicine ( Site 1052)	Bangkok	Krung Thep Maha Nakhon
Thailand	Research Institute for Health Sciences ( Site 1053)	Chiang Mai
United States	Augusta University ( Site 0010)	Augusta	Georgia
United States	Kentucky Pediatric/Adult Research Inc ( Site 0011)	Bardstown	Kentucky
United States	Charlottesville Medical Research Center, LLC ( Site 0007)	Charlottesville	Virginia
United States	Rapid Medical Research, Inc. ( Site 0037)	Cleveland	Ohio
United States	Clinical Research of South Florida ( Site 0036)	Coral Gables	Florida
United States	Certified Research Associates ( Site 0041)	Cortland	New York
United States	University of Texas Medical Branch at Galveston ( Site 0038)	Galveston	Texas
United States	Healthcare Research Network LLC ( Site 0035)	Hazelwood	Missouri
United States	Texas Center For Drug Development ( Site 0013)	Houston	Texas
United States	Holston Medical Group ( Site 0030)	Kingsport	Tennessee
United States	Alliance for Multispecialty Reseach, LLC ( Site 0021)	Las Vegas	Nevada
United States	Solaris Clinical Research, LLC ( Site 0003)	Meridian	Idaho
United States	Acevedo Clinical Research Associates ( Site 0001)	Miami	Florida
United States	Laser Surgery Care ( Site 0018)	New York	New York
United States	Weill Cornell Medicine ( Site 0046)	New York	New York
United States	Health Research of Hampton Roads, Inc. ( Site 0015)	Newport News	Virginia
United States	Coastal Carolina Research Center ( Site 0043)	North Charleston	South Carolina
United States	Valley Clinical Trials Inc. ( Site 0002)	Northridge	California
United States	Preferred Primary Care Physicians ( Site 0032)	Pittsburgh	Pennsylvania
United States	Inland Empire Clinical Trials, LLC ( Site 0025)	Rialto	California
United States	Clinical Research Partners, LLC. ( Site 0004)	Richmond	Virginia
United States	Rochester Clinical Research, Inc. ( Site 0008)	Rochester	New York
United States	PMG Research of Salisbury ( Site 0009)	Salisbury	North Carolina
United States	J Lewis Research Inc/Foothill Family Clinic South ( Site 0006)	Salt Lake City	Utah
United States	Alta California Medical Group ( Site 0031)	Simi Valley	California
United States	J Lewis Research Inc/Jordan River Family Medicine ( Site 0023)	South Jordan	Utah
United States	Encompass Clinical Research ( Site 0028)	Spring Valley	California
United States	Moffitt Cancer Center ( Site 0017)	Tampa	Florida
United States	Cotton-O'Neil Clinical Research Center ( Site 0044)	Topeka	Kansas
United States	Crossroads Clinical Research LLC ( Site 0027)	Victoria	Texas
United States	Diablo Clinical Research, Inc ( Site 0042)	Walnut Creek	California
United States	Heartland Research Associates, LLC ( Site 0034)	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Colombia,  Czechia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Human Papillomavirus (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 human papillomavirus (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 42
Secondary	Incidence of Human Papillomavirus (HPV) 6/11-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 human papillomavirus (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 42
Secondary	Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies	Serum antibodies to HPV types are measured with competitive Luminex immunoassay (cLIA). Geometric mean titers of antibodies to HPV types will be calculated by exponentiating the mean estimates of natural logarithm of the anti-HPV titers.	1 month postdose 3 (Month 7)
Secondary	Percentage of Participants who Seroconvert to Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, and 58	Seroconversion is defined as changing a participant's serostatus from seronegative at Day 1 to seropositive by 4 weeks postdose 3. A participant with anti-HPV competitive Luminex immunoassay (cLIA) titer at or above the serostatus cutoff of the cLIA for a given HPV type is considered seropositive for that HPV type.	1 month postdose 3 (Month 7)
Secondary	Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE)	An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Solicited injection-site AEs such as redness/erythema, swelling, and tenderness/pain at the injection site will be recorded.	Up to 5 days after any vaccination
Secondary	Percentage of Participants with Elevated Temperature (Fever)	Participants are asked to record oral body temperatures. The percentage of participants with elevated temperature (=37.8°C or 100.0°F) will be assessed.	Up to 5 days after any vaccination
Secondary	Percentage of Participants Who Report at Least 1 Systemic Adverse Event	An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs.	Up to 15 days after any vaccination
Secondary	Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)	A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is another important medical event deemed such by medical or scientific judgment.	Up to 15 days after any vaccination
Secondary	Percentage of Participants who Experience at Least 1 Serious Vaccine-Related Adverse Event	A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is another important medical event deemed such by medical or scientific judgment. An SAE that is considered by an investigator (a qualified physician) to be vaccine-related will be reported during entire study period.	Up to Month 42

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary