This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01461096
First received: October 26, 2011
Last updated: February 10, 2017
Last verified: December 2016
October 26, 2011
February 10, 2017
March 2012
December 2015   (Final data collection date for 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 ]

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.

Time to the First New Persistent Infection of HPV 6, 11, 16, or 18 [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
Persistent infection is defined as infection confirmed by positive HPV polymerase chain reaction (PCR) results at two consecutive visits at least 16 weeks apart without an intervening negative result. Participants with pre-existing HPV infection at baseline are still evaluable for the primary endpoint if they develop new persistent infection of an HPV type not present at baseline.
Complete list of historical versions of study NCT01461096 on ClinicalTrials.gov Archive Site
  • Number of Participants With Biopsy-proven High-grade Anal Intraepithelial Neoplasia (HGAIN) Occurrences and Reoccurrences After Week 52 [ Time Frame: From Week 52 to participant's last study visit, for up to 4 years ]
    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.
  • Number of Participants With Anal Cytological Abnormality Occurrences [ Time Frame: At baseline, Week 52, Week 104 and Week 156 ]
    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).
  • 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 [ Time Frame: From baseline to participant's last study visit, for up to 4 years ]
    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).
  • Time to First New Persistent Oral HPV Infection of Vaccine Types Detected From Oral Rinse [ Time Frame: From baseline to participant's last study visit, for up to 4 years ]

    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.

  • Number of biopsy-proven high-grade anal intraepithelial neoplasia (HGAIN) occurrences after Week 52 [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
    HGAIN is defined as anal intraepithelial neoplasia (AIN)2, AIN3, AIN2-3, or carcinoma in situ found in the intra-anal or perianal region. Number of biopsy-proven or provider-detected anal, perianal, or oral condyloma after Week 52.
  • Number of anal cytological abnormality occurrences [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
    Anal cytologic abnormalities include atypical squamous cells of undetermined significance (ASCUS); atypical squamous cells, cannot exclude HSIL (ASC-H); low-grade squamous intraepithelial lesion (LSIL); or high-grade squamous intraepithelial lesion (HSIL).
  • Occurrence of Grade 3 or 4 adverse events (AEs) that are possibly, probably, or definitely related to the vaccine, as determined by the local investigator [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • Time interval of the first new oral HPV infection of vaccine types detected from oral rinse [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • Geometric mean titers of antibody levels of each vaccine type as measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) at each scheduled follow-up time point [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • HPV infection types for participants who develop HGAIN or condyloma post-randomization [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • Number of surgical or medical treatments required for HGAIN and/or genital warts [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • Acceptability of high-resolution anoscopy (HRA) and other ablative surgical treatments for AIN or condyloma [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • Detection of non-vaccine type HPV DNA in anal or oral specimens [ Time Frame: Measured through participant's last study visit, which will occur 3 to 4 years after the last participant is enrolled in the study ]
  • Positive cytology, anal biopsy, and anal HPV DNA PCR results at screening and entry [ Time Frame: Measured at study entry ]
Not Provided
Not Provided
 
Quadrivalent HPV Vaccine to Prevent Anal HPV in HIV-infected Men and Women
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Prevention
HIV Infections
  • Biological: Quadrivalent HPV Vaccine
    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.
  • Biological: Placebo Vaccine for Male Participants Only
    Participants were prescribed one IM injection of the placebo vaccine in the upper arm or thigh at baseline and Weeks 8 and 24.
  • Biological: Placebo Vaccine for Female Participants Only
    Participants were prescribed one IM injection of the placebo vaccine in the upper arm or thigh at baseline and Weeks 8 and 24.
  • Experimental: Quadrivalent HPV Vaccine
    Participants were prescribed the quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
    Intervention: Biological: Quadrivalent HPV Vaccine
  • Placebo Comparator: Placebo Vaccine
    Participants were prescribed the placebo vaccine at baseline and Weeks 8 and 24.
    Interventions:
    • Biological: Placebo Vaccine for Male Participants Only
    • Biological: Placebo Vaccine for Female Participants Only

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
575
January 2016
December 2015   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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:

    1. Absolute neutrophil count (ANC) greater than 750 cells/mm^3
    2. Hemoglobin greater than or equal to 9.0 g/dL
    3. Platelet count greater than or equal to 75,000/mm^3
    4. Serum creatinine less than or equal to three times the upper limit of normal (ULN)
    5. 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
    6. 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

Exclusion Criteria:

  • 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
  • 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
Sexes Eligible for Study: All
27 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Brazil,   Puerto Rico,   United States
 
 
NCT01461096
A5298
11798 ( Registry Identifier: DAIDS ES Registry Number )
Yes
Not Provided
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Timothy J. Wilkin, MD, MPH Cornell Clinical Research Site
Study Chair: Ross D. Cranston, MD University of Pittsburgh
National Institute of Allergy and Infectious Diseases (NIAID)
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP