HPV-SAVE_Merck_Sub-Study for Preventing Recurrence of HSIL
A Multicenter, Randomized Controlled Trial of the Efficacy, Safety and Immunogenicity of HPV Vaccination in Preventing Recurrence of HSIL in HIV-positive MSM
1 other identifier
interventional
228
1 country
4
Brief Summary
Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Infection by certain high-risk oncogenic types of HPV (HR-HPV) is the major cause of several cancers in men, notably squamous cell carcinoma (SCC) of the anal canal. Rates of anal infection with these HR-HPV strains, and the resultant high-grade anal dysplasia and anal cancer are much higher in men who have sex with men (MSM) than in the general population. Co-infection with human immunodeficiency virus (HIV) further amplifies this burden, making the rates of anal SCC in HIV-positive MSM higher than the historic rates of cervical cancer prior to the adoption of routine cervical cytology screening. Despite these alarming statistics, there are no established protocols for optimal screening and treatment of anal HPV and cancer precursors, nor has there been any widespread rollout of organized screening programs anywhere in Canada. Further, not only does HPV directly cause significant disease in these men, but there is growing epidemiologic evidence that HPV infection may enhance sexual transmission of HIV. These significant knowledge gaps translate into fundamental deficiencies in care for HIV-positive MSM. The HPV Screening and Vaccine Evaluation in MSM (HPV-SAVE) study team was funded by the Canadian Institutes of Health Research (CIHR) via its Boys' and Men's Health Team Grant Competition. It aims to recruit a large group of MSM from various Ontario and Vancouver clinics, in order to carry out a number of different studies. The HPV-SAVE team brings together community and internationally-recognized experts in HPV and HIV disease and mucosal immunology, to better define the optimal approaches for primary and secondary prevention and treatment of HPV-associated anal disease among HIV-positive MSM, and to explore biological mechanistic evidence regarding the potential role of HPV as a co-factor for HIV transmission. This will yield critical information which can lead to improvement in the health of MSM, and will provide a foundation on which to build large-scale screening and treatment trials on a national level. A key part of this research program involves an analysis of the potential role played by the HPV vaccine in the overall management of HIV-positive MSM. Planned vaccine-related projects include:
- A mixed-methods analysis of the knowledge, attitudes, and acceptability of HPV vaccination amongst HIV-positive MSM, through quantitative (e.g. cross-sectional survey) and qualitative (e.g. in-depth interviews) means.
- A comprehensive assessment of the 9-valent HPV vaccine in HIV-positive MSM, including safety and immunogenicity, as well as its potential role in secondary prevention of high-grade anal dysplasia. This is the study on which the current proposal is based.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2022
Typical duration for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 9, 2019
CompletedFirst Posted
Study publicly available on registry
May 13, 2019
CompletedStudy Start
First participant enrolled
September 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2026
CompletedJune 13, 2022
June 1, 2022
3.5 years
May 9, 2019
June 9, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The proportion of participants in each arm with biopsy-proven HGAIN (AIN-2/3).
Secondary Prevention. "Successful treatment" refers to a biopsy-proven HGAIN lesion treated with ablative therapy electrocautery (EC) with repeat biopsy of the same lesion 2-3 months thereafter demonstrating no further evidence of HGAIN (meaning that the follow-up biopsy is either AIN-1 or normal).
24 months, following successful treatment of HGAIN
Secondary Outcomes (1)
The geometric mean titres (GMT) of antibody to each vaccine type above a pre-specified, validated cut-off. F
24 months, following successful treatment of HGAIN
Other Outcomes (1)
Change in anal carriage of vaccine HPV types. Repeated detection of anal HPV will indicate the duration of carriage. This will be compared between the early and delayed vaccine groups.
24 months
Study Arms (2)
Immediate Vaccination
EXPERIMENTALAdministration of dose #1 of 9-valent HPV vaccination will be given at baseline visit, dose #2 at month 2, and dose #3 at month 6.
Delayed Vaccination
ACTIVE COMPARATORAdministration of dose #1 of 9-valent HPV vaccination will be given at month 12, dose #2 at month 14, and dose #3 at month 18.
Interventions
Gardasil-9 is a novel, 9-valent HPV recombinant vaccine, which expands the coverage of oncogenic HPV types, with the addition of HPV types 31, 33, 45, 52, and 58 to the existing quadrivalent vaccine types. The addition of these five oncogenic types is estimated to improve cancer coverage to 90% (versus 70% for the quadrivalent vaccine) \[38\]. With its expanded coverage of oncogenic HPV types, its proven efficacy in primary prevention and its potential role in mitigating HGAIN recurrences.
Eligibility Criteria
You may qualify if:
- Males, aged ≥ 18 years at baseline;
- Physician or laboratory documentation of HIV-1 infection (enzyme-linked immunosorbent assay \[ELISA\] and Western Blot);
- AIN-2 or -3 found on biopsy of anal canal lesion(s), and willingness of the subject to undergo ablative therapy which is standard of care in most screening clinics;
- History of any sexual activity with men, or both men and women, where sexual activity is defined as oral, vaginal, or anal intercourse;
- For those on cART, the participant must be on a stable regimen (i.e. virologically suppressed with HIV-1 ribonucleic acid (RNA) below the assay's limit of detection for minimum six months). This will minimize confounding from dramatic shifts in viral load and/or cluster of differentiation 4 (CD4) count;
- For those individuals that are not on cART, there must be no immediate plans to initiate cART in the next six months. There will be no lower limit cut-off for CD4 count;
- An ability to give informed consent;
- An ability to attend clinic for all study visits.
You may not qualify if:
- Known hypersensitivity to any component of the HPV vaccine (e.g. Saccharomyces cerevisiae yeast, Amorphous Aluminium Hydroxyphosphate Sulfate adjuvant);
- Current or prior history of cancer of the anogenital regions (e.g. penile, anal, or rectal) or of the oropharyngeal area (e.g. oral cavity, upper airway).
- Previous HPV immunization.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Health Network, Torontolead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (4)
BC Centre for Disease Control
Vancouver, British Columbia, V5Z 4R4, Canada
University of British Columbia
Vancouver, British Columbia, V6T 1Z4, Canada
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9, Canada
University Health Network - Toronto General Hospital
Toronto, Ontario, M5G 2C4, Canada
Related Publications (5)
Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.
PMID: 9516219BACKGROUNDHammer SM, Eron JJ Jr, Reiss P, Schooley RT, Thompson MA, Walmsley S, Cahn P, Fischl MA, Gatell JM, Hirsch MS, Jacobsen DM, Montaner JS, Richman DD, Yeni PG, Volberding PA; International AIDS Society-USA. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA. 2008 Aug 6;300(5):555-70. doi: 10.1001/jama.300.5.555.
PMID: 18677028BACKGROUNDChiao EY, Krown SE, Stier EA, Schrag D. A population-based analysis of temporal trends in the incidence of squamous anal canal cancer in relation to the HIV epidemic. J Acquir Immune Defic Syndr. 2005 Dec 1;40(4):451-5. doi: 10.1097/01.qai.0000159669.80207.12.
PMID: 16280701BACKGROUNDSwedish KA, Factor SH, Goldstone SE. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clin Infect Dis. 2012 Apr;54(7):891-8. doi: 10.1093/cid/cir1036. Epub 2012 Jan 30.
PMID: 22291111BACKGROUNDJoura EA, Garland SM, Paavonen J, Ferris DG, Perez G, Ault KA, Huh WK, Sings HL, James MK, Haupt RM; FUTURE I and II Study Group. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ. 2012 Mar 27;344:e1401. doi: 10.1136/bmj.e1401.
PMID: 22454089BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Irving Salit, MD
Toronto General Hospital, University Health Network
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Immunodeficiency Clinic, Toronto General Hospital
Study Record Dates
First Submitted
May 9, 2019
First Posted
May 13, 2019
Study Start
September 1, 2022
Primary Completion
March 1, 2026
Study Completion
May 1, 2026
Last Updated
June 13, 2022
Record last verified: 2022-06