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

NCT01461096 | Completed Phase 3 Results DMC

• 2 other identifiers: A529811798
• Study Type: interventional
• Target: 575
• Locations: 3 countries
• Sites: 24

Brief 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. 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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Number of Participants With Biopsy-proven High-grade Anal Intraepithelial Neoplasia (HGAIN) Occurrences and Reoccurrences After Week 52

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

• Number of Participants With Anal Cytological Abnormality Occurrences

  At baseline, Week 52, Week 104 and Week 156

• 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

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

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

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

Study Arms (2)

Quadrivalent HPV Vaccine

EXPERIMENTAL

Participants were prescribed the quadrivalent HPV vaccine at baseline and Weeks 8 and 24.

Biological: Quadrivalent HPV Vaccine

Placebo Vaccine

PLACEBO COMPARATOR

Participants were prescribed the placebo vaccine at baseline and Weeks 8 and 24.

Biological: Placebo Vaccine for Male Participants Only; Biological: Placebo Vaccine for Female Participants Only

Interventions

Quadrivalent HPV Vaccine BIOLOGICAL

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.

Quadrivalent HPV Vaccine

Placebo Vaccine for Male Participants Only BIOLOGICAL

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

Placebo Vaccine for Female Participants Only BIOLOGICAL

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

Eligibility Criteria

• Age: 27 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• Expected treatment of hepatitis B or hepatitis C virus with immunomodulatory agents in the 7 months after entry
• Breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (24)

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Denver Public Health CRS

Denver, Colorado, 80204, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center CRS

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-360, Brazil

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (5)

• 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.

  PMID: 18614927 BACKGROUND

• 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.

  PMID: 18525266 BACKGROUND

• 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).

  BACKGROUND

• 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.

  PMID: 34907980 DERIVED

• 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.

  PMID: 29659751 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Timothy J. Wilkin, MD, MPH

  Cornell Clinical Research Site

  STUDY CHAIR

• Ross D. Cranston, MD

  University of Pittsburgh Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2011
• First Posted: October 27, 2011
• Study Start: March 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: November 2, 2021
• Results First Posted: February 7, 2017

Record last verified: 2021-10

Locations

PR (1); BR (1); US (22)