HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV

NCT03284866 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: AMC-099NCI-2016-00841UM1CA121947
• Study Type: interventional
• Target: 536
• Locations: 5 countries
• Sites: 6

Brief Summary

This randomized phase III trial studies how well human papillomavirus (HPV) vaccine therapy works in reducing high-grade cervical lesions in patients with human immunodeficiency virus (HIV) and HPV. Vaccines made from HPV peptides or antigens may help the body build an effective immune response to kill the HPV virus and prevent cervical lesions from developing or coming back after being removed.

Conditions

HIV Infection; AIDS-Related Human Papillomavirus Infection; High Grade Cervical Squamous Intraepithelial Neoplasia

Outcome Measures

Primary Outcomes (1)

• Occurrence of cervical high-grade squamous intraepithelial lesions (HSIL) or cervical cancer

  For each arm (vaccine and placebo), the event rate will be estimated using its point estimate and 95% Poisson confidence intervals. Poisson regression analyses will be used to compare the two arms with respect to event rate. In addition, time to event from week 4 to 52 will be described using the Kaplan-Meier method for each arm, and the two arms will be compared with respect to time to event using the log-rank test.

  After week 4 study visit to week 52 post-randomization

Secondary Outcomes (14)

• Occurrence of cervical HSIL from weeks 52-104

  After week 52 to week 104

• Role of baseline types and quantity of HPV as predictors of sustained absence

  At baseline and week 4

• Role of presence of HSIL at baseline as a predictor of sustained absence

  At baseline and week 4

• Role of CD4+ cell count as a predictor of sustained absence

  At baseline and week 4

• Role of plasma HIV-1 RNA as a predictor of sustained absence

  At baseline and week 4

Other Outcomes (6)

• HPV type distributions

  Up to week 104

• HPV strain variant analysis of cervical and vulvar HSIL specimens

  Up to week 104

• Tissue microarray library of cervical specimens for biomarker analysis and discovery

  Up to week 104

Study Arms (2)

Arm I, recombinant HPV 9-valent vaccine

EXPERIMENTAL

Patients receive Recombinant Human Papillomavirus Nonavalent Vaccine (Gardasil 9) IM at baseline, 4, and 26 weeks in the absence of disease progression or unacceptable toxicity, with sample collection for Laboratory Biomarker Analysis.

Other: Laboratory Biomarker Analysis; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

Arm II, saline

PLACEBO COMPARATOR

Patients receive saline placebo vaccine IM at baseline, 4, and 26 weeks, with sample collection for Laboratory Biomarker Analysis.

Other: Laboratory Biomarker Analysis; Other: Saline

Interventions

Saline OTHER

Given IM

Also known as: Sodium Chloride 0.9%

Arm II, saline

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I, recombinant HPV 9-valent vaccine; Arm II, saline

Recombinant Human Papillomavirus Nonavalent Vaccine BIOLOGICAL

Given IM

Also known as: Gardasil 9, Nonavalent HPV VLP Vaccine, Recombinant HPV Nonavalent Vaccine, Recombinant Human Papillomavirus 9-valent Vaccine, Recombinant HPV 9-valent Vaccine

Arm I, recombinant HPV 9-valent vaccine

Eligibility Criteria

• Age: 25 Years+
• Sex: female
• 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, or documentation of receipt of antiretroviral therapy; Note: the term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating country and validated internally; WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment; a reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a western blot or a plasma HIV-1 RNA viral load
• HPV positive by the GeneXpert hrHPV assay with HPV16, HPV 18/45, or HPV31/33/35/52/58 detected; Note: participants who are hrHPV positive with only HPV51/59 or HPV 39/68/56/66 detected are not eligible
• Receipt of ART for at least 180 days prior to randomization
• Participants of childbearing potential, defined as a sexually mature woman who: (1) has not undergone a hysterectomy or bilateral oophorectomy or (2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), must have a negative urine or serum pregnancy test within 3 weeks prior to enrollment and agree to use an effective form of contraception (e.g., barrier contraception or hormonal contraception), delaying pregnancy for at least 12 months and ideally for the duration of the study; Note: those willing to participate delay pregnancy for at least 6 months, while receiving the recombinant human papillomavirus nonavalent (9vHPV) vaccine (or placebo)
• If the participant is of childbearing potential, she should be at least 3 months postpartum
• Karnofsky score \>= 70%
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Current sexually transmitted infection (STI) requiring treatment (women may participate after adequate treatment, at the discretion of the treating provider)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gardasil or Gardasil 9
• Uncontrolled intercurrent illness that would limit compliance with study requirements
• Prior hysterectomy with removal of the cervix
• Prior treatment for cervical HSIL
• Prior history of cervical, vulvar, or vaginal cancer
• Cervical, vulvar, or vaginal lesions suspicious for cancer based on clinical appearance (e.g. necrotic, ulcerated, and/or fungating masses), unless biopsies show no invasive cancer
• Known bleeding diathesis
• Prior HPV vaccination
• Current or planned use of anticoagulants other than aspirin or non-steroidal anti-inflammatory agents

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• University of Arkansas: collaborator
• AIDS and Cancer Specimen Resource: collaborator
• Merck Sharp & Dohme LLC: collaborator
• The Emmes Company, LLC: collaborator
• University of California, Los Angeles: collaborator

Study Sites (6)

Moi University School of Medicine

Eldoret, Kenya

Location

UNC Project Malawi

Lilongwe, Malawi

Location

African Cancer Institute at Stellenbosch

Cape Town, South Africa

Location

University of the Witwatersrand

Johannesburg, South Africa

Location

Uganda Cancer Institute

Kampala, Uganda

Location

University of Zimbabwe

Harare, Zimbabwe

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Human Papillomavirus Recombinant Vaccine nonavalent; Sodium Chloride

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)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Carla Chibwesha

  University of Witwatersrand, South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2017
• First Posted: September 15, 2017
• Study Start: July 31, 2019
• Primary Completion: November 26, 2024
• Study Completion: August 5, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1); MA (1); ZI (1); ZA (2); UG (1)