Vaccine Therapy in Preventing HPV in HIV-Positive Women in India

February 19, 2024 updated by: AIDS Malignancy Consortium

A Single-Arm, Open-Label Pilot Study of the Safety and Immunogenicity of the Merck Quadrivalent Human Papillomavirus Vaccine Among HIV-Positive Women in India

RATIONALE: Vaccines made from virus proteins may help the body build an effective immune response to prevent cervical cancer.

PURPOSE: This pilot study is looking at the side effects of a human papillomavirus vaccine and how well it works in preventing cervical cancer in women in India with HIV-1 infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Assess the safety of the Gardasil® quadrivalent human papillomavirus (HPV) (types 6, 11, 16,18) virus-like-particle vaccine with vs without prior exposure to one or more of the HPV types in the vaccine in HIV-positive women in Chennai, India.
  • Determine the effect of the vaccine on HIV viral load and CD4+/CD8+ levels in these patients.
  • Determine the proportion of these patients who respond serologically to the HPV vaccine and the kinetics of their response.

Secondary

  • Determine the prevalence and incidence of cervical intraepithelial neoplasia in these patients.
  • Determine the spectrum of cervical HPV types in these patients at baseline, 9 months, and 1 year after vaccination.

OUTLINE: This is a multicenter study.

Patients receive quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and once in weeks 8 and 24.

Patients undergo cervical cell, buccal cell, and blood sample collection at baseline and periodically after vaccination for immunologic and virologic studies. Cervical cytology specimens are examined by polymerase chain reaction to detect HPV 6, 11, 16, or 18 DNA, as well as 35 other HPV types. Blood samples are analyzed for CD4+/CD8+ cell count, plasma HIV-1 RNA levels, and serum HPV antibody titers for HPV types 6, 11, 16, and 18. Some plasma samples will be stored for future HPV pseudovirion neutralization assays.

After completion of study therapy, patients are followed periodically for up to 12 months.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
      • Chennai, India, 600113
        • YRG Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot before study entry

    • HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test

  • Meets 1 of the following criteria:

    • Nadir CD4 level of ≤ 350 cells/mm³ and receiving highly active antiretroviral therapy (HAART) for at least 6 months before study entry
    • Nadir CD4 level of > 350 cells/mm³ and not receiving HAART at the time of study entry
  • No known history of high-grade CIN or cervical cancer

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • ANC > 750 cells/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100,000/mm³
  • Serum creatinine ≤ 3 times upper limit of normal (ULN)
  • AST and ALT ≤ 3.0 times ULN
  • Conjugated (direct) bilirubin ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active drug or alcohol use or dependence that would interfere with adherence to study requirements, in the opinion of the site Investigator
  • No serious illness requiring systemic treatment and/or hospitalization within the past 45 days
  • No allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

  • More than 45 days since prior systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin

    • Routine standard of care, including hepatitis B, influenza, and tetanus vaccines are allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gardasil Vaccination
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Genetic: DNA analysis
Weeks 0, 2, 10, 26, and 52.
Other Names:
  • HIV viral load test and HPV neutralization assays.
Genetic: polymerase chain reaction
Screening, week 36, and week 52.
Other: cytology specimen collection procedure
Screening, week 36, and week 52.
Procedure: colposcopic biopsy
Screening, week 36, and week 52.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0
Time Frame: 52 weeks from study entry
Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients
52 weeks from study entry
Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count
Time Frame: Screening/Week 0, Weeks 2, 10, 26, and 52.
Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests
Screening/Week 0, Weeks 2, 10, 26, and 52.
Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28
Time Frame: Week 28
Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline
Week 28
Number of Patients With a Significant Increase in HIV Viral Load
Time Frame: Screening/week 0, weeks, 2, 10, 26 and 52
Number of patients with a significant increase in HIV viral load defined as > 1 log increase in HIV load from baseline on 2 consecutive occasions
Screening/week 0, weeks, 2, 10, 26 and 52
Number of Patients With Detectable Antibodies to HPV-6
Time Frame: 28 weeks
Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline
28 weeks
Number of Patients With Detectable Antibodies to HPV-11
Time Frame: 28 weeks
Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline
28 weeks
Number of Patients With Detectable Antibodies to HPV-18
Time Frame: 28 weeks
Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline
28 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AIDS Malignancy Consortium

Collaborators

National Cancer Institute (NCI)
The Emmes Company, LLC

Investigators

  • Principal Investigator: N. Kumarasamy, MD, YRG Care
  • Study Chair: Joel Palefsky, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

April 25, 2008

First Submitted That Met QC Criteria

April 25, 2008

First Posted (Estimated)

April 28, 2008

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMC-054
  • U01CA121947 (U.S. NIH Grant/Contract)
  • CDR0000593634 (Other Identifier: NCI)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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