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

• ClinicalTrials.gov Identifier: NCT04199689
• Recruitment Status: Active, not recruiting
• First Posted: December 16, 2019
• Last Update Posted: August 18, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: December 12, 2019
• First Posted Date: December 16, 2019
• Last Update Posted Date: August 18, 2022
• Actual Study Start Date: February 27, 2020
• Estimated Primary Completion Date: August 20, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 12, 2019)

Incidence of Human Papillomavirus (HPV)16/18/31/33/45/52/58-related 6-month Persistent Oral Infection [ Time Frame: Up to Month 42 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 12, 2019)

• Incidence of Human Papillomavirus (HPV) 6/11-related 6-month Persistent Oral Infection [ Time Frame: Up to Month 42 ]
  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.
• Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies [ Time Frame: 1 month postdose 3 (Month 7) ]
  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.
• Percentage of Participants who Seroconvert to Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 [ Time Frame: 1 month postdose 3 (Month 7) ]
  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.
• Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE) [ Time Frame: Up to 5 days after any vaccination ]
  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.
• Percentage of Participants with Elevated Temperature (Fever) [ Time Frame: Up to 5 days after any vaccination ]
  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.
• Percentage of Participants Who Report at Least 1 Systemic Adverse Event [ Time Frame: Up to 15 days after any vaccination ]
  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.
• Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) [ Time Frame: Up to 15 days after any vaccination ]
  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.
• Percentage of Participants who Experience at Least 1 Serious Vaccine-Related Adverse Event [ Time Frame: Up to Month 42 ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief 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 in this study 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
• Condition: Papillomavirus Infections

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 Names:

  • GARDASIL®9
  • V503
• Other: Placebo (Saline for Injection)
  0.9% sodium chloride given as a 0.5-mL intramuscular injection

Study Arms

• Experimental: 9vHPV vaccine
  Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6
  Intervention: Biological: 9vHPV Vaccine
• Placebo Comparator: Placebo
  Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6
  Intervention: Other: Placebo (Saline for Injection)

Publications *

• 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.
• Morais E, Kothari S, Roberts C, Yen G, Chen YT, Lynam M, Pedrós 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 12, 2019): 6000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 20, 2024
• Estimated Primary Completion Date: August 20, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)
• 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
• 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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Healthy male participants between the ages of 20 and 45 years (inclusive)

• Ages: 20 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Brazil, Colombia, Czechia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Mexico, Peru, Spain, Taiwan, Thailand, United States

Administrative Information

• NCT Number: NCT04199689
• Other Study ID Numbers: V503-049; 2019-003236-23 ( Other Identifier: EudraCT Number ); V503-049 ( Other Identifier: Merck ); 205346 ( Registry Identifier: JAPIC-CTI )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: August 2022