Quadrivalent HPV Vaccine to Prevent Anal HPV in HIV-infected Men and Women
NCT ID: NCT01461096
Last Updated: 2021-11-02
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE3
575 participants
INTERVENTIONAL
2012-03-31
2016-01-31
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
QUADRUPLE
Study Groups
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Quadrivalent HPV Vaccine
Participants were prescribed the quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
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.
Placebo Vaccine
Participants were prescribed the placebo vaccine at baseline and Weeks 8 and 24.
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.
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.
Interventions
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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.
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.
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.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
27 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Timothy J. Wilkin, MD, MPH
Role: STUDY_CHAIR
Cornell Clinical Research Site
Ross D. Cranston, MD
Role: STUDY_CHAIR
University of Pittsburgh Medical Center
Locations
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UCLA CARE Center CRS
Los Angeles, California, United States
Stanford AIDS Clinical Trials Unit CRS
Palo Alto, California, United States
UCSD Antiviral Research Center CRS
San Diego, California, United States
Ucsf Hiv/Aids Crs
San Francisco, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Denver Public Health CRS
Denver, Colorado, United States
Northwestern University CRS
Chicago, Illinois, United States
Rush University CRS
Chicago, Illinois, United States
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, United States
Boston Medical Center CRS
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
Washington University Therapeutics (WT) CRS
St Louis, Missouri, United States
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, United States
Weill Cornell Chelsea CRS
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Columbia P&S CRS
New York, New York, United States
University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, United States
Chapel Hill CRS
Chapel Hill, North Carolina, United States
Cincinnati Clinical Research Site
Cincinnati, Ohio, United States
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, United States
Houston AIDS Research Team CRS
Houston, Texas, United States
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, , Brazil
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, , Puerto Rico
Countries
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References
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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.
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.
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.
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.
Other Identifiers
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11798
Identifier Type: REGISTRY
Identifier Source: secondary_id
A5298
Identifier Type: -
Identifier Source: org_study_id