Nine-valent HPV Vaccine to Prevent Persistent Oral HPV Infection in Men Living With HIV

NCT ID: NCT04255849

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 700 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-23
• Study Completion Date: 2026-07-01

Brief Summary

This is a randomized, double-blinded, placebo-controlled Phase III interventional trial of the nine-valent HPV vaccine (9vHPV) to prevent persistent oral HPV infection in adult men living with HIV.

Detailed Description

Men ages 20-50 years living with HIV will be enrolled at affiliated clinical sites of the University of Puerto Rico, the National Institute of Public Health, Mexico, and University of São Paulo, Brazil. Participants will have a baseline blood draw for serum HPV antibodies and stored plasma, an oral rinse for HPV testing, HPV methylation, and EBV co-infection, stored anal and genital samples for HPV testing, as well as a baseline questionnaire about risk factors for oral HPV infection and oropharyngeal cancer.

Seven hundred participants will be randomized in a 1:1 allocation to receive 9vHPV or placebo at Day 1, Month 2, and Month 6. Randomization will be stratified based on clinical site and age (20-30, 31-40, 41- 50 years). The age range of enrolled participants will be monitored to ensure enrollment of an approximately even distribution of participants across the age range. Enrollment will take place during the first 28 months of this study.

Follow-up testing for oral HPV will be conducted at Months 2, 6, 7, 12 and every 6 months thereafter up to 54 months post-vaccination. The rationale for oral testing at Months 2 and 6 is to identify participants who are oral HPV positive prior to receiving the full 3 doses of vaccine. In addition, an optional collection of anal canal and genital specimens (penile head, shaft, scrotum) will occur at Day 1, Months 7, 12 and every 6 months thereafter up to 54 months post-vaccination in those that specifically provided consent. These specimens will be stored for future medical research and will not be analyzed as part of this study. Serum will be stored for HPV antibody testing at month 7, 12 and every 12 months thereafter. Additionally, 20ml of whole blood will be collected beginning at Month 12 and every 12 months thereafter for DNA methylation of biological aging and circulating tumor HPV DNA (ctHPVDNA) analysis. Participants will undergo a follow-up questionnaire on risk factors for oral HPV and oropharyngeal cancer. Participants will be assessed for adverse events at each follow-up visit. This is a 5-year study. Participants who received placebo will be offered 9vHPV vaccine when the study is unblinded.

The trial analyses will be case driven with case counting commencing at Month 7, one month post-dose 3. The primary analysis will take place when at least 14 cases of the primary endpoint (incident persistent oral HPV infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, or 58) have been observed.

Early data on the baseline oral HPV prevalence among ULACNet-201 participants suggests an approximately 50% lower prevalence of oral HPV than anticipated. This suggests that oral HPV incidence will likely be significantly lower than anticipated. The reasons for this are not yet clear. To help speed the time until the required number of primary endpoint events is accrued, the number of events needed for the primary endpoint have been changed from 31 to 14. The sample size will also be increased by 40% (from 500 to 700 participants), of which a majority will be enrolled from sites in Mexico. Adding 200 participants will increase the number of follow-up visits where additional eligible primary endpoint events can occur. This allows for additional sample size should loss to follow-up increase. In addition, follow-up time will be extended from 42 months post-vaccination to 54 months post-vaccination to allow for accrual of at least 14 events.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma; HIV-1-infection; HPV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

9-valent HPV vaccine

Participants receive 9-valent HPV vaccine 0.5mL at entry, Month 2 and Month 6

Group Type: EXPERIMENTAL

9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58)

Intervention Type: BIOLOGICAL

Gardasil-9 HPV vaccine

Saline Placebo

Participants receive 0.9% NaCl 0.5 mL at entry, Month 2 and Month 6

Group Type: PLACEBO_COMPARATOR

Saline Placebo

Intervention Type: OTHER

Saline Placebo

Interventions

9 valent human papillomavirus vaccine (Types 6, 11, 16, 18, 31, 33, 45, 52, 58)

Gardasil-9 HPV vaccine

Intervention Type: BIOLOGICAL

Saline Placebo

Saline Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• HIV-1 infection
• Receipt of antiretroviral therapy for at least 6 months
• Sexually active in the past 6 months; sexual activity is defined as insertive penile-vaginal sex, receptive or insertive penile-anal sex, oral-anal sex, or oral-genital sex Willingness to comply with three-dose vaccine schedule and subsequent six-month visits for up to four years after randomization.

Exclusion Criteria

• Have a history of oropharyngeal cancer (OPC) or other HPV-related cancer or have suspected OPC or other HPV-related cancer;
• Have received any doses of a licensed or experimental HPV vaccine or have participated in an HPV vaccine study,
• Have a history of anaphylaxis to vaccines or are allergic to any vaccine component (e.g.aluminum, yeast, benzonase);
• Have received any blood products within six months of enrollment, or are currently taking immune-suppressants.
• Currently have warts/lesions in the oral cavity.
• Plan to relocate during the study period.
• Have AIDS-defining condition within 6 months prior to study entry.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: collaborator

University of Puerto Rico

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

Instituto Nacional de Salud Publica, Mexico

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Grant Ellsworth, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Universidade de São Paulo

São Paulo, São Paulo, Brazil

Instituto Nacional de Salud Pública, Mexico

Cuernavaca, Morelos, Mexico

University of Puerto Rico AIDS Clinical Trials Unit

San Juan, Purto Rico, Puerto Rico

Countries

Brazil; Mexico; Puerto Rico

References

Giuliano AR, Beltrame A, Villa LL, Lazcano-Ponce E, Santana-Bagur J, Allen-Leigh B, Portillo-Romero AJ, Sahasrabuddhe VV, House MG, Brofsky E, Galan de Paula L, Carvalho da Silva R, Schell MJ, Rathwell J, Isaacs-Soriano K, Fan W, Mello C, Ellsworth GB, Wilkin T. Design of a multicenter, randomized, double-blinded, placebo-controlled phase III trial evaluating the 9-valent human papillomavirus (HPV) vaccine to prevent persistent oral HPV infection in men living with human immunodeficiency virus: ULACNet trial 201. Vaccine. 2025 Aug 13;61:127447. doi: 10.1016/j.vaccine.2025.127447. Epub 2025 Jul 2.

Reference Type: DERIVED

PMID: 40609265 (View on PubMed)

Other Identifiers

U54CA242639

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-11021038

Identifier Type: -

Identifier Source: org_study_id