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

AIDS Malignancy Consortium

Status and phase: Active, not recruiting; Phase 3

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

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

Study type: Interventional

Funder types: Other; NETWORK; Industry; NIH

Identifiers

NCT03284866

NCI-2016-00841 (Registry Identifier)

UM1CA121947 (U.S. NIH Grant/Contract)

AMC-099 (Other Identifier)

Details and patient eligibility

About

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.

Full description

At screening, potential participants will be tested for cervical human papillomavirus (HPV) infection (GeneXpert hrHPV assay and HPV DNA PCR) and undergo cervical colposcopy to confirm the absence of cervical cancer. If eligible, the participant will be randomized to receive either the 9-valent HPV vaccine or saline placebo.

Participants will return 4 and 26 weeks later for the second dose of vaccine or placebo. At week 4, participants will have cervical colposcopy and undergo cryotherapy or loop electrosurgical excisional procedure (LEEP) as appropriate. Participants undergoing cervical cryotherapy will have cervical biopsies before the treatment. Participants will be followed with HPV testing (Gene Xpert and HPV DNA PCR) at weeks 26, 52, 78, and 104, and will have cervical cytology and colposcopy with biopsies at weeks 26, 52, and 104.

Enrollment: 536 patients

Sex: Female

Ages: 25+ years old

Volunteers: No Healthy Volunteers

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, 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

Exclusion criteria

• 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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536 participants in 2 patient groups, including a placebo group

Arm I, recombinant HPV 9-valent vaccine

Experimental group

Description:

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.

Treatment:

Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

Other: Laboratory Biomarker Analysis

Arm II, saline

Placebo Comparator group

Description:

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

Treatment:

Other: Laboratory Biomarker Analysis

Other: Saline