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HIV InfectionsPhase 3NCT01461096

Quadrivalent HPV Vaccine to Prevent Anal HPV in HIV-infected Men and Women

A Phase 3 study testing Quadrivalent HPV Vaccine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Men who have sex with men (MSM) have an increased risk of developing anal human papillomavirus (HPV) infections, which can be a risk factor for anal cancer. HIV-infected women are also at risk of anal cancer. Read more about this study

Who is it for?
Ages 27 years and older
Conditions the study is for
HIV Infections
What is being tested?
Quadrivalent HPV Vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
575 participants
Where
24 sitesin 3 countries
Study dates
Mar 2012to Jan 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 27 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. More information on this criterion can be found in the protocol.
  • Laboratory values obtained within 45 days prior to entry by any U.S. laboratory that has a Clinical Laboratory Improvement Amendment (CLIA) certification or its equivalent, or at any network-approved non-U.S. laboratory that operates in accordance with Good Clinical Practices and participates in appropriate external quality assurance programs:
  • Absolute neutrophil count (ANC) greater than 750 cells/mm^3
  • Hemoglobin greater than or equal to 9.0 g/dL
  • Platelet count greater than or equal to 75,000/mm^3
  • Serum creatinine less than or equal to three times the upper limit of normal (ULN)
Show all 15Show fewer
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) less than or equal to five times the ULN
  • Total or conjugated (direct) bilirubin less than or equal to 2.5 times the ULN
  • For men, receptive anal sex (defined as receptive penile-anal sex or receptive oral-anal sex with another man) within 1 year prior to entry
  • Anal cytology result from specimen obtained within 45 days prior to entry
  • HRA performed within 45 days prior to entry by a certified HRA provider with no evidence of invasive or microinvasive anal cancer by anal biopsy or by visual inspection if no biopsy was obtained. Note: refer to protocol for more information about HRA certification process.
  • For women, gynecologic examination (including screening for cervical disease by exfoliative cytology with or without colposcopy) within 45 days prior to entry.
  • For women of reproductive potential, a negative serum or urine pregnancy test within 45 days prior to study entry by any U.S. laboratory that has a CLIA certification or its equivalent, or at any network-approved non-U.S. laboratory that operates in accordance with Good Clinical Practices and participates in appropriate external quality assurance programs. More information on this criterion can be found in the protocol.
  • Confirmation of the availability of the anal swab, vaginal swab (women only) and Scope oral rinse specimens for HPV DNA PCR obtained at screening. The site must confirm that these samples have been entered into the Laboratory Data Management System (LDMS).
  • Ability and willingness of participant or legal representative to provide informed consent

Who cannot join

  • History or current biopsy diagnosis of invasive or microinvasive cancer, i.e.:
  • For all participants: anal or oropharyngeal cancer
  • For men: penile cancer
  • For women: cervical, vulvar, or vaginal cancer
  • More information on this criterion can be found in the protocol.
  • Anal, cervical, or vaginal cytological results suspicious for invasive carcinoma at any point prior to entry
Show all 16Show fewer
  • Topical or surgical treatment for intra- or perianal intraepithelial neoplasia or condyloma within 6 months prior to entry. More information on this criterion can be found in the protocol.
  • Prior receipt of one or more doses of an HPV vaccine
  • Receipt of anticoagulants other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to entry
  • Known allergy/sensitivity or any hypersensitivity to yeast or any of the components of the study product or its formulation. More information on this criterion can be found in the protocol.
  • Active drug or alcohol use or dependence or other condition that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to entry
  • Hemophilia or other bleeding diatheses
  • Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids other than inhaled corticosteroids or prednisone less than or equal to 10 mg (or equivalent), investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. NOTE: Routine standard-of-care vaccines (including hepatitis A, hepatitis B, influenza, pneumococcal, and tetanus vaccines) are not exclusionary.
  • Expected treatment of hepatitis B or hepatitis C virus with immunomodulatory agents in the 7 months after entry
  • Breastfeeding

Trial locations and contacts

24 sites in 3 countries.

24 sites in 3 countries

United States22 sites
  • University of Colorado Hospital CRS

    Aurora, Colorado, 80045

  • Massachusetts General Hospital CRS (MGH CRS)

    Boston, Massachusetts, 02114

  • Boston Medical Center CRS

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27599

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Rush University CRS

    Chicago, Illinois, 60612

  • Cincinnati Clinical Research Site

    Cincinnati, Ohio, 45219

  • Denver Public Health CRS

    Denver, Colorado, 80204

  • Houston AIDS Research Team CRS

    Houston, Texas, 77030

  • UCLA CARE Center CRS

    Los Angeles, California, 90035

  • Weill Cornell Chelsea CRS

    New York, New York, 10011

  • NY Univ. HIV/AIDS CRS

    New York, New York, 10016

  • Columbia P&S CRS

    New York, New York, 10032-3732

  • New Jersey Medical School Clinical Research Center CRS

    Newark, New Jersey, 07103

  • Stanford AIDS Clinical Trials Unit CRS

    Palo Alto, California, 94304-5350

  • University of Pittsburgh CRS

    Pittsburgh, Pennsylvania, 15213

  • The Miriam Hospital Clinical Research Site (TMH CRS) CRS

    Providence, Rhode Island, 02906

  • University of Rochester Adult HIV Therapeutic Strategies Network CRS

    Rochester, New York, 14642

  • UCSD Antiviral Research Center CRS

    San Diego, California, 92103

  • Ucsf Hiv/Aids Crs

    San Francisco, California, 94110

  • Washington University Therapeutics (WT) CRS

    St Louis, Missouri, 63110-1010

Other trials in United States

Brazil1 site
  • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

    Rio de Janeiro, 21040-360

Other trials in Brazil

Puerto Rico1 site
  • Puerto Rico AIDS Clinical Trials Unit CRS

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: A Randomized, Double-Blinded, Placebo-Controlled, Phase III Trial of the Quadrivalent HPV Vaccine to Prevent Anal Human Papillomavirus Infection in HIV-Infected Men and Women

Men who have sex with men (MSM) have an increased risk of developing anal human papillomavirus (HPV) infections, which can be a risk factor for anal cancer. HIV-infected women are also at risk of anal cancer. This study will evaluate the effectiveness of the Food and Drug Administration (FDA)-approved quadrivalent HPV vaccine, Gardasil, at preventing anal HPV infection in HIV-infected MSM and HIV-infected women.

Read the detailed description

Anal HPV infection can be a risk factor for anal cancer, which is a common non-AIDS-defining cancer among HIV-infected MSM. Screening for anal cancer is not widely available and can be difficult to implement. People who receive the FDA-approved quadrivalent HPV vaccine, Gardasil, may have a reduced risk of developing anal HPV infection, which may in turn reduce the risk of developing anal cancer. The purpose of this study is to evaluate the effectiveness of the quadrivalent HPV vaccine, Gardasil, at reducing the incidence of anal HPV infections in HIV-infected MSM and HIV-infected women.

This study enrolled HIV-infected MSM and HIV-infected women. Participants were randomly assigned to receive the HPV vaccine or a placebo vaccine. At the screening study visit, participants underwent a physical examination, blood collection, anal swab procedure, oral examination, questionnaires, a high-resolution anoscopy (HRA), and if female, a pregnancy test, vaginal swab, and gynecologic exam. At the entry study visit, participants underwent most of the procedures performed at screening (with the exception of an HRA and a gynecologic exam if female) plus a saliva test. Participants received the HPV vaccine or placebo as an injection into their upper arm or thigh on Day 0 and Weeks 8 and 24. Study staff called participants 2 to 3 days after each vaccination for follow-up monitoring. Additional study visits and procedures occurred at Week 28, Week 52, and every 26 weeks thereafter for at least 3 years and for a maximum of 4 years after the last participant was enrolled in the study. Female participants also had a gynecologic exam at screening, Week 52, and every 52 weeks thereafter; a pregnancy test at screening, baseline, Week 8, Week 24, and as indicated; and self-collected vaginal swabs at screening, entry, Week 28, Week 52, and every 26 weeks thereafter. Peripheral blood mononuclear cells (PBMCs) were collected from some participants at entry, Week 28, and study exit.

The DSMB held a total of four reviews for the study. After careful review of the outcome data in the 4th review held on September 2, 2015, the DSMB commended the study team for a well-run study that provided important results and recommended stopping the study early due to futility. The recommendation was based on meeting the pre-specified criteria for inadequate conditional power to detect a treatment difference at 50% information.

The study was prematurely discontinued on December 31, 2015, which was around eight months earlier than originally planned. With approval from SASC, the study team managed to offer high resolution anoscopy (HRA) procedures to participants whose most recent anal Pap tests showed abnormal results, unless the HRA took place on or after 09/01/14.

Conditions
HIV Infections
Being tested
Quadrivalent HPV Vaccine, Placebo Vaccine for Male Participants Only, Placebo Vaccine for Female Participants Only
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Quadrivalent HPV VaccineBiological

    Participants were prescribed one intramuscular (IM) injection of the quadrivalent HPV vaccine in the upper arm or thigh at baseline and Weeks 8 and 24.

  • Placebo Vaccine for Male Participants OnlyBiological

    Participants were prescribed one IM injection of the placebo vaccine in the upper arm or thigh at baseline and Weeks 8 and 24.

  • Placebo Vaccine for Female Participants OnlyBiological

    Participants were prescribed one IM injection of the placebo vaccine in the upper arm or thigh at baseline and Weeks 8 and 24.

Study groups in NCT01461096
Study groupRoleWhat they receive
Quadrivalent HPV VaccineExperimentalParticipants were prescribed the quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Receives: Biological: Quadrivalent HPV Vaccine
Placebo VaccinePlacebo comparatorParticipants were prescribed the placebo vaccine at baseline and Weeks 8 and 24.
Receives: Biological: Placebo Vaccine for Male Participants Only; Biological: Placebo Vaccine for Female Participants Only

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to the First New Persistent Infection of HPV 6, 11, 16, or 18

    The outcome for this evaluation was time to the first new persistent infection of any of HPV 6, 11, 16, or 18. Persistent infection was defined as an infection confirmed by positive anal HPV PCR results at 2 consecutive visits at least 16 weeks apart without an intervening negative result. A participant who had a positive measurement on his/her last measurement with no consecutive confirmatory measurement was considered as having a persistent infection. Participants with pre-existing HPV infection at baseline were evaluable for the primary outcome if they were PCR negative for at least one of the four vaccine HPV types at baseline.

    NOTE: Use 5th and 10th percentiles in years from baseline to the first new persistent infection as the summary measure.

    Measured: From baseline to participant's last study visit, for up to 4 years

Secondary outcomes (4)
  1. Number of Participants With Biopsy-proven High-grade Anal Intraepithelial Neoplasia (HGAIN) Occurrences and Reoccurrences After Week 52

    HGAIN was defined as AIN2 (moderate dysplasia, with no mention of AIN grade III), AIN3 (severe dysplasia, carcinoma in-situ, or AIN grade II/III), high grade AIN not specified, or adenocarcinoma in situ found in the intra-anal or perianal region.

    Measured: From Week 52 to participant's last study visit, for up to 4 years

  2. Number of Participants With Anal Cytological Abnormality Occurrences

    Anal cytologic abnormalities include: atypical squamous cells undetermined significance (ASCUS), atypical squamous cells favor high-grade SIL/squamous cell carcinoma (ASC-H), low-grade squamous intraepithelial lesion/mild dysplasia/HPV (LSIL), or high-grade SIL/moderate dysplasia to severe dysplasia/carcinoma in situ/features of invasion (HSIL).

    Measured: At baseline, Week 52, Week 104 and Week 156

  3. Number of Participants With Grade 3 or 4 Adverse Events (AEs) That Were Possibly, Probably, or Definitely Related to the Vaccine, as Determined by the Local Investigator

    To grade diagnoses, signs and symptoms, and laboratory results, sites must refer to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, august 2009).

    Measured: From baseline to participant's last study visit, for up to 4 years

  4. Time to First New Persistent Oral HPV Infection of Vaccine Types Detected From Oral Rinse

    The outcome for this evaluation was time to the first new persistent infection of any of oral HPV 6, 11, 16, or 18. Persistent infection was defined as an infection confirmed by positive oral HPV PCR results at 2 consecutive visits at least 16 weeks apart without an intervening negative result. A participant who had a positive measurement on his/her last measurement with no consecutive confirmatory measurement was considered as having a persistent infection. Participants with pre-existing HPV infection at baseline were evaluable for the primary endpoint if they were PCR negative for at least one of the four vaccine HPV types at baseline.

    NOTE: Use 5th and 10th percentiles in years from baseline to the first new persistent infection as the summary measure.

    Measured: From baseline to participant's last study visit, for up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2011 (estimated)
  2. Study startMar 2012
  3. Primary completionDec 2015
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
575 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01461096
Sponsor's protocol ID
A5298
Other IDs
11798
Status last verified
Oct 2021
First submitted
26 Oct 2011
Last updated
2 Nov 2021
Data monitoring committee
Yes

Publications

  • D'Souza G, Wiley DJ, Li X, Chmiel JS, Margolick JB, Cranston RD, Jacobson LP. Incidence and epidemiology of anal cancer in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr. 2008 Aug 1;48(4):491-9. doi: 10.1097/QAI.0b013e31817aebfe.

    PubMed 18614927
  • Piketty C, Selinger-Leneman H, Grabar S, Duvivier C, Bonmarchand M, Abramowitz L, Costagliola D, Mary-Krause M; FHDH-ANRS CO 4. Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy. AIDS. 2008 Jun 19;22(10):1203-11. doi: 10.1097/QAD.0b013e3283023f78.

    PubMed 18525266
  • The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).

  • Kang M, Umbleja T, Ellsworth G, Aberg J, Wilkin T. Effects of Sex, Existing Antibodies, and HIV-1-Related and Other Baseline Factors on Antibody Responses to Quadrivalent HPV Vaccine in Persons With HIV. J Acquir Immune Defic Syndr. 2022 Apr 1;89(4):414-422. doi: 10.1097/QAI.0000000000002891.

    PubMed 34907980
  • Wilkin TJ, Chen H, Cespedes MS, Leon-Cruz JT, Godfrey C, Chiao EY, Bastow B, Webster-Cyriaque J, Feng Q, Dragavon J, Coombs RW, Presti RM, Saah A, Cranston RD. A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298. Clin Infect Dis. 2018 Oct 15;67(9):1339-1346. doi: 10.1093/cid/ciy274.

    PubMed 29659751

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Quadrivalent HPV Vaccine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Brazil, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to the First New Persistent Infection of HPV 6, 11, 16, or 18 (time frame: From baseline to participant's last study visit, for up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01461096, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.

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