A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents and Young Adults
Background:
Human papilloma virus (HPV) is one of the most common sexually transmitted diseases and a
significant cause of cutaneous genital warts and anogenital cancer.
Infection with high-risk, oncogenic HPV types, most commonly types 16 and 18, is associated
with low and high-grade cervical cellular abnormalities that are precursors to invasive
cervical cancer, as well as vulvar and anal cancer, while HPV types 6 and 11 are associated
with genital warts.
Persistence of HPV infection is more common in individuals with or at risk for chronic
immunosuppression and HIV-infected individuals have a higher prevalence of HPV infection and
HPV-associated anogential disease compared to age-matched HIV-negative controls.
Study Objectives:
To assess the safety and immunogenicity of quadrivalent human papillomavirus (types 6, 11,
16, 18) recombinant vaccine in HIV-infected preadolescents, adolescents and young adults
12-26 years of age.
To determine whether there are differences in HPV vaccine immunogenicity between
HIV-infected and HIV negative age-matched controls.
To determine whether there are differences in HPV vaccine immunogenicity between
HIV-infected patients receiving highly active antiretroviral therapy (HAART) and those not
receiving HAART with similar CD4 and viral load parameters at entry.
To determine whether HPV vaccination alters HIV-1 RNA levels.
To investigate the impact of CD4 count and HIV-1 RNA levels on HPV vaccine immunogenicity.
To characterize HPV DNA positivity in the study cohort populations through oral/buccal and
anogenital sampling at baseline.
To characterize HPV and HIV knowledge and risk and sexual behaviors in the study cohort
populations.
Eligibility:
Individual Cohorts
Cohort 1: HIV-positive, CD4 cell count greater than or equal to 350 cells/mm(3), HIV-1 RNA
level by RT PCR less than or equal to 20,000 copies/ml, on stable HAART regimen for greater
than or equal to 6 months.
Cohort 2: HIV-infected, CD4 cell count greater than or equal to 500 cells/mm(3), HIV-1 RNA
level by RT PCR less than or equal to 20,000 copies/ml, on no antiretroviral treatment.
Cohort 3: healthy, HIV-negative controls All Cohorts
Females and males age 12 to 26 years
Patients must have a hemoglobin greater than or equal to 10.0 gm/dL, neutrophil count (ANC)
greater than or equal to 1500/mm(3), platelet count greater than or equal to 75,000/mm(3)
and PT or PTT less than or equal to 1.5 times ULN (with the exception of patients with known
clotting disorders or lupus anticoagulant); SGPT/SGOT < 2/5 times ULN, total bilirubin less
than or equal to 1.5 times ULN unless attributable to protease inhibitor therapy.
Patients must test negative for hepatitis B virus and hepatitis C virus, unless the result
is consistent with prior vaccination or prior infection with full recovery.
No use of investigational agents within 4 weeks of study enrollment or use of
immunosuppressive or immunomodulating agents within 8 weeks of study entry.
Study Design:
This is a non-randomized, prospective, phase I study of quadrivalent human papillomavirus
(types 6, 11, 16, 18) recombinant vaccine.
The study includes 3 cohorts of pre-adolescents, adolescents and young adults 12-26 years of
age as outlined under Eligibility Criteria. Each cohort will enroll 35 patients.
All study subjects will receive three doses of HPV vaccine at 0, 2 and 6 months administered
IM.
Study participants will be monitored at months 0, 1, 2, 3, 6, 7, and 12 (+/- 2 weeks for
each visit, and every 6 months (+/- 30 days) thereafter for 48 months total.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in antibody titers following quadrivalent HPV vaccination in HIV-infected subjects; Safety of quadrivalent HPV vaccination in HIV-infected subjects.
Lauren V Wood, M.D.
Principal Investigator
National Cancer Institute (NCI)
United States: Federal Government
090024
NCT00798265
October 2008
February 2013
Name | Location |
---|---|
National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |