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HPV-SAVE: 9-Valent HPV Vaccine for High-Grade Anal Dysplasia

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ClinicalTrials.gov Identifier: NCT03947775
Recruitment Status : Not yet recruiting
First Posted : May 13, 2019
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Irving Salit, University Health Network, Toronto

Brief Summary:

Infection by certain high-risk oncogenic types of Human Papillomavirus (HR-HPV) is the major cause of several cancers in men, notably squamous cell carcinoma (SCC) of the anal canal. Rates of high-grade anal dysplasia and anal cancer are much higher in men who have sex with men (MSM) than in the general population. Rates of anal SCC in HIV-positive MSM are higher than the historic rates of cervical cancer prior to the adoption of routine cervical cytology screening. Despite these statistics, there are no established protocols for optimal screening and treatment of anal cancer precursors. Further, there is growing evidence that HPV may enhance sexual transmission of HIV. These significant knowledge gaps translate into fundamental deficiencies in the care for HIV-positive MSM.

The HPV Screening and Vaccine Evaluation in MSM (HPV-SAVE) study team aims to recruit a large group of MSM from various Ontario and Vancouver clinics in order to carry out 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) 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 b) 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 upon which the current proposal is based.


Condition or disease Intervention/treatment Phase
Anal Intraepithelial Neoplasia Anal Cancer Human Papilloma Virus Drug: 9-valent HPV vaccination Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 206 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This will be a randomized, open-label multicentre clinical trial consisting of two arms (immediate versus delayed vaccination) assessing the efficacy, safety and immunogenicity of the 9-valent recombinant HPV vaccine in HIV-positive males 18 years of age and older.

Participants for the proposed study will be recruited from Canadian centres in Toronto, Ottawa, Kingston and Vancouver through ongoing projects making up our HPV-SAVE team grant.

Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multicenter, Randomized Controlled Trial of 9-valent HPV Vaccination in Preventing Recurrence of High-grade Anal Dysplasia in HIV-positive MSM
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Immediate Vaccination
Administration 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.
Drug: 9-valent HPV vaccination
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.
Other Name: Gardasil-9

Active Comparator: Delayed Vaccination
Administration of dose #1 of 9-valent HPV vaccination will be given at month 24, dose #2 at month 26, and dose #3 at month 30.
Drug: 9-valent HPV vaccination
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.
Other Name: Gardasil-9




Primary Outcome Measures :
  1. The proportion of participants in each arm with biopsy-proven HGAIN (AIN-2/3). [ Time Frame: 24 months, following successful treatment of HGAIN ]
    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).


Secondary Outcome Measures :
  1. The geometric mean titres (GMT) of antibody to each vaccine type above a pre-specified, validated cut-off. F [ Time Frame: 24 months, following successful treatment of HGAIN ]
    Immunogenicity. or this measure, immunogenicity will be measured as the proportion of participants with GMT of antibody to each vaccine type above a pre-specified, validated cut-off, using a Luminex-based immunoassay [40-42]. Currently, these values for the HPV types present in the 9-valent vaccine are: HPV-6, 30 milli-Merck units/ml (mMU/mL); HPV-11, 16 mMU/mL; HPV-16, 20 mMU/mL; HPV-18, 24 mMU/mL; HPV-31, 10 mMU/mL; HPV-33, 8 mMU/mL; HPV-45, 8 mMU/mL; HPV-52, 8 mMU/mL; and HPV-58, 8 mMU/mL .


Other Outcome Measures:
  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. [ Time Frame: 24 months ]
    Immunogenicity



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   History of any sexual activity with men, or both men and women, where sexual activity is defined as oral, vaginal, or anal intercourse.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males, aged ≥ 18 years at baseline;
  2. Laboratory documentation of HIV-1 infection (enzyme-linked immunosorbent assay [ELISA] and Western Blot);
  3. AIN-2 or -3 found on biopsy of anal canal lesion(s), and willingness to undergo ablative therapy;
  4. History of any sexual activity with men, or both men and women, where sexual activity is defined as oral, vaginal, or anal intercourse;
  5. 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;
  6. 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;
  7. An ability to give informed consent;
  8. An ability to attend clinic for all study visits.

Exclusion Criteria:

  1. Known hypersensitivity to any component of the HPV vaccine (e.g. Saccharomyces cerevisiae yeast, Amorphous Aluminium Hydroxyphosphate Sulfate adjuvant);
  2. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03947775


Contacts
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Contact: Irving Salit, MD 416-340-3697 irving.salit@uhn.ca
Contact: Marian Claudio 416-340-4800 ext 5628 marian.claudio@uhn.ca

Locations
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Canada, British Columbia
BC Centre for Disease Control
Vancouver, British Columbia, Canada, V5Z 4R4
University of British Columbia
Vancouver, British Columbia, Canada, V6T 1Z4
Canada, Ontario
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada, K1Y 4E9
University Health Network - Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Irving Salit, MD Toronto General Hospital, University Health Network

Publications:
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Responsible Party: Irving Salit, Immunodeficiency Clinic, Toronto General Hospital, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03947775     History of Changes
Other Study ID Numbers: 53205
First Posted: May 13, 2019    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Irving Salit, University Health Network, Toronto:
Men who have sex with men
Human immunodeficiency virus
Human papillomavirus
Vaccine
Gardasil
Anal Intraepithelial Neoplasia
Anal Cancer
9-valent
Additional relevant MeSH terms:
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Papilloma
Anus Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs