Clinical trial NCT04199689: Efficacy Against Oral Persistent Infection, Immunogenicity and Safety of the 9-valent Human Papillomavirus Vaccine (9vHPV) in Men Aged 20-45 Years (V503-049)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Papillomavirus Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-12-16
Enrollment: 6033
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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 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
* 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, 6, 7, 10, 16, or 18 are met

Primary outcomes:
measure: Incidence of HPV 16/18/31/33/45/52/58-related 6-month Persistent Oral Infection
timeFrame: Up to Month 90
Secondary outcomes:
measure: Incidence of HPV 6/11-related 6-month Persistent Oral Infection
timeFrame: Up to Month 90
measure: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies
timeFrame: 1 month postdose 3 (Month 7)
measure: Percentage of Participants who Seroconvert to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
timeFrame: 1 month postdose 3 (Month 7)
measure: Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE)
timeFrame: Up to 5 days after any vaccination
measure: Percentage of Participants with Elevated Temperature (Fever)
timeFrame: Up to 5 days after any vaccination
measure: Percentage of Participants Who Report at Least 1 Systemic AE
timeFrame: Up to 15 days after any vaccination
measure: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)
timeFrame: Up to 15 days after any vaccination
measure: Percentage of Participants who Experience at Least 1 Serious Vaccine-Related AE
timeFrame: Up to Month 90
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Valley Clinical Trials Inc. ( Site 0002)
state: California
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC ( Site 0025)
state: California
city: Simi Valley
country: United States
facility: Alta California Medical Group ( Site 0031)
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research ( Site 0028)
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc ( Site 0042)
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida ( Site 0036)
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates ( Site 0001)
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center ( Site 0017)
state: Florida
city: Augusta
country: United States
facility: Augusta University ( Site 0010)
state: Georgia
city: Meridian
country: United States
facility: Solaris Clinical Research, LLC ( Site 0003)
state: Idaho
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center ( Site 0044)
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC ( Site 0034)
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric/Adult Research Inc ( Site 0011)
state: Kentucky
city: Hazelwood
country: United States
facility: Healthcare Research Network LLC ( Site 0035)
state: Missouri
city: Las Vegas
country: United States
facility: Alliance for Multispecialty Reseach, LLC ( Site 0021)
state: Nevada
city: Cortland
country: United States
facility: Certified Research Associates ( Site 0041)
state: New York
city: New York
country: United States
facility: Laser Surgery Care ( Site 0018)
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine ( Site 0046)
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc. ( Site 0008)
state: New York
city: Salisbury
country: United States
facility: PMG Research of Salisbury ( Site 0009)
state: North Carolina
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc. ( Site 0037)
state: Ohio
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians ( Site 0032)
state: Pennsylvania
city: North Charleston
country: United States
facility: Coastal Carolina Research Center ( Site 0043)
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group ( Site 0030)
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston ( Site 0038)
state: Texas
city: Houston
country: United States
facility: Texas Center For Drug Development ( Site 0013)
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research LLC ( Site 0027)
state: Texas
city: Salt Lake City
country: United States
facility: J Lewis Research Inc/Foothill Family Clinic South ( Site 0006)
state: Utah
city: South Jordan
country: United States
facility: J Lewis Research Inc/Jordan River Family Medicine ( Site 0023)
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC ( Site 0007)
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc. ( Site 0015)
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC. ( Site 0004)
state: Virginia
city: Wilrijk
country: Belgium
facility: University of Antwerp ( Site 0352)
state: Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Gasthuisberg ( Site 0353)
state: Vlaams-Brabant
city: Tienen
country: Belgium
facility: Femicare VZW ( Site 0350)
state: Vlaams-Brabant
city: Salvador
country: Brazil
facility: Hospital Santo Antonio - Obras Sociais Irma Dulce ( Site 0101)
state: Bahia
city: Natal
country: Brazil
facility: CPCLIN ( Site 0100)
state: Rio Grande Do Norte
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisa Clinica II - ICHC - FMUSP ( Site 0102)
city: Medellin
country: Colombia
facility: Fundacion Centro de Investigacion Clinica CIC ( Site 0153)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa Ltda. ( Site 0152)
state: Atlantico
city: Chia
country: Colombia
facility: Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0156)
state: Cundinamarca
city: Brno
country: Czechia
facility: Centrum ambulantni gynekologie a primarni pece ( Site 0401)
state: Brno-mesto
city: Olomouc
country: Czechia
facility: G-CENTRUM Olomouc s.r.o. ( Site 0400)
city: Praha 2
country: Czechia
facility: MediStar s.r.o. ( Site 0403)
city: Praha 5
country: Czechia
facility: FN Motol ( Site 0402)
city: Dijon
country: France
facility: CHU Dijon Bourgogne - Hopital F. Mitterrand ( Site 0223)
state: Cote-d Or
city: Montpellier
country: France
facility: Hopital Saint Eloi ( Site 0504)
state: Herault
city: Paris
country: France
facility: Hopital Cochin ( Site 0506)
state: Ile-de-France
city: Rennes
country: France
facility: C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0507)
state: Ille-et-Vilaine
city: Nantes
country: France
facility: CHU Nantes - Hopital Hotel Dieu ( Site 0510)
state: Loire-Atlantique
city: Frankfurt am Main
country: Germany
facility: Infektiologikum Frankfurt-Sachsenhausen ( Site 0456)
state: Hessen
city: Berlin
country: Germany
facility: Epimed GmbH ( Site 0450)
city: Berlin
country: Germany
facility: Klinische Forschung Berlin ( Site 0454)
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf ( Site 0451)
city: Kfar Saba
country: Israel
facility: Meir Medical Center ( Site 0602)
state: Central
city: Tel Aviv
country: Israel
facility: Maccabi Health Services Medical Center ( Site 0604)
state: HaMerkaz
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0601)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center. Ein Kerem ( Site 0600)
city: Rome
country: Italy
facility: Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 0551)
state: Roma
city: Padova
country: Italy
facility: Azienda Ospedaliera - Universita di Padova ( Site 0555)
state: Veneto
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico di Bari ( Site 0550)
city: Catania
country: Italy
facility: AOU Policlinico Vittorio Emanuele ( Site 0552)
city: Roma
country: Italy
facility: Universita di Roma "La Sapienza" ( Site 0553)
city: Hachioji
country: Japan
facility: P-One Clinic, Keikokai Medical Corp. ( Site 1101)
state: Tokyo
city: Fukuoka
country: Japan
facility: Sagiyama Urology Clinic ( Site 1116)
city: Fukuoka
country: Japan
facility: Souseikai PS Clinic ( Site 1103)
city: Kumamoto
country: Japan
facility: Souseikai Nishikumamoto Hospital ( Site 1104)
city: Osaka
country: Japan
facility: Medical Corporation Heishinkai OPHAC Hospital ( Site 1105)
city: Osaka
country: Japan
facility: Nomura Clinic Namba ( Site 1114)
city: Osaka
country: Japan
facility: Medical Corporation Seiwakai Hayakawa Clinic ( Site 1113)
city: Tokyo
country: Japan
facility: Doujin Memorial Medical Foundation, Meiwa Hospital ( Site 1111)
city: Tokyo
country: Japan
facility: Taisei Clinic ( Site 1109)
city: Tokyo
country: Japan
facility: Medical Corporation Mori to Umi Tokyo Tokyo Kamata Hospital ( Site 1112)
city: Tokyo
country: Japan
facility: Naoko Dermatology Clinic ( Site 1107)
city: Tokyo
country: Japan
facility: Medical Corporation Shinanokai Shinanozaka Clinic ( Site 1106)
city: Tokyo
country: Japan
facility: Medical Corporation Iseikai My City Clinic ( Site 1108)
city: Tokyo
country: Japan
facility: Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 1102)
city: Tokyo
country: Japan
facility: Kusunoki Clinic ( Site 1110)
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital ( Site 0952)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 0954)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 0953)
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital ( Site 0951)
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital ( Site 0950)
city: Cuernavaca
country: Mexico
facility: Instituto Nacional de Salud Publica ( Site 0202)
state: Morelos
city: Cdmx
country: Mexico
facility: Arke Estudios Clinicos S.A. de C.V. ( Site 0203)
city: Chihuahua
country: Mexico
facility: Icaro Investigaciones en Medicina S.A. de C.V. ( Site 0200)
city: Veracruz
country: Mexico
facility: ARKE Estudios Clinicos S.A de C.V ( Site 0211)
city: Iquitos
country: Peru
facility: Asociacion Civil Selva Amazonica ( Site 0252)
state: Loreto
city: Lima
country: Peru
facility: Policlinico Universidad Nacional Mayor de San Marcos ( Site 0257)
city: Lima
country: Peru
facility: Investigaciones Medicas en Salud - INMENSA ( Site 0255)
city: Lima
country: Peru
facility: Instituto de Investigacion Nutricional - Anexo Huascar ( Site 0251)
city: Lima
country: Peru
facility: Asociacion Via Libre ( Site 0250)
city: Badalona
country: Spain
facility: Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0755)
state: Barcelona
city: Centelles
country: Spain
facility: CAP Centelles ( Site 0751)
state: Barcelona
city: L Hospitalet De Llobregat
country: Spain
facility: ICO L Hospitalet ( Site 0754)
state: Barcelona
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1003)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 1002)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 1000)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation.Linkou Branch ( Site 1001)
city: Bangkok
country: Thailand
facility: Armed Forces Research Institute of Medical Sciences ( Site 1051)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Vaccine Trial Center Faculty of Tropical Medicine ( Site 1052)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 1050)
state: Krung Thep Maha Nakhon
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences ( Site 1053)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.