Safety of and Immune Response to a Novel Human Papillomavirus Vaccine in HIV Infected Children
Condition: HIV Infections; Sexually Transmitted Diseases
MeSH terms: Sexually Transmitted Diseases
Intervention: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV); Placebo/QHPV
Intervention description: QHPV at week 0, 8, 24 and 96.; Placebo at week 0, 8, 24 and QHPV at week 96, 104, 120.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 130.0
Sex: All
Minimum age: 7 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: HPV

Summary:

      The purpose of this study is to determine the safety of and immune response to a new human
      papillomavirus (HPV) vaccine in HIV (Human immunodeficiency virus) infected children between
      the ages of 7 and 12 years.
    

Eligibility criteria:

        Inclusion Criteria

        Children ages ≥ 7 to < 12 years of age.

        A confirmed diagnosis of HIV infection, defined as two positive assays from two different
        samples. The two results may be in any combination of the following:

          -  at any age: Deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), Ribonucleic
             acid (RNA) PCR

          -  age > 4 weeks: p24 antigen detection

          -  age >18 months: licensed ELISA (Enzyme-linked immunosorbent assay) with confirmatory
             Western Blot

        CD4% ≥ 15 at the time of screening is required (Note that this is a minimum requirement,
        and that for Stratum C the CD4% needs to be ≥ 25).

        For Strata A and B: Currently stable (≥ 3 months) on highly active antiretroviral therapy
        (HAART) regimen, defined as three or more antiretrovirals from at least two different
        therapeutic classes, or therapy with the combination of azidothymidine, lamivudine, and
        abacavir.

        For stratum C no antiretroviral therapy is required.

        Parent or legal guardian able and willing to provide signed informed consent.

        Negative urine pregnancy test sensitive to 25 International Unit (IU) beta-human chorionic
        gonadotropin (HCG) for girls who are menstruating (child bearing potential).

        Female study volunteers who are participating in sexual activity that could lead to
        pregnancy must agree to use two reliable methods of contraception, one of which must be a
        barrier method. A barrier method of contraception (condoms or cervical cap) together with
        another reliable form of contraception (condoms a , with a spermicidal agent; a diaphragm
        or cervical cap with spermicide; an intrauterine device [IUD]; or hormonal-based
        contraception) must be used while on this study. Condoms are recommended because their
        appropriate use is the only contraception method effective for preventing HIV-1
        transmission

        Males participating in the study must not attempt to impregnate a woman, or participate in
        sperm donation programs. Males engaging in sexual activity that could lead to pregnancy
        must use a condom.

        Exclusion Criteria

        Body temperature ≥ 101 F or ≥ 38.3 C, orally determined, within 72 hours prior to the first
        and each subsequent injection. Subjects may be vaccinated any time in the next seven days
        thereafter, provided that the site investigator is satisfied that the febrile illness has
        ended.

        Total bilirubin ≥ 5 x Upper Limit of Normal (ULN) at screening.

        Alanine transaminase (ALT) or serum glutamic pyruvic transaminase (SGPT) ≥ 5 x ULN at
        screening in the absence of other explained causes (as determined by the site investigator)
        at screening.

        Serum creatinine ≥ 1.5 mg/dL at screening.

        Absolute neutrophil count ≤ 750 cells/mm3 at screening.

        Hemoglobin ≤ 9.9 g/dL at screening.

        Platelet count ≤ 75,000 cells/mm³ at screening.

        Presence of an acute opportunistic non-bacterial or bacterial infection requiring therapy
        at the time of enrollment; the subject may be entered once he/she is stable on appropriate
        anti-infective therapy.

        Chemotherapy for active malignancy.

        Other known or suspected disease of the immune system, or immunosuppressive therapy.

        Prior treatment with immunosuppressive or immunomodulation therapy within 60 days of
        screening.

        Prior treatment with three or more week-long courses of corticosteroids (≥ 2.0 mg/kg or ≥
        20 mg total of prednisone-equivalent) within one year of screening; or any systemic (oral
        or parenteral) steroids (≥ 2.0 mg/kg or ≥ 20 mg total of prednisone-equivalent for ≥ 3
        days) within 30 days of study entry.

        Prior vaccinations with inactivated vaccines received within two weeks of any dose of study
        vaccine, and no other vaccinations may be planned for two weeks after each dose of study
        vaccine.

        Prior vaccinations with live vaccines received within three weeks before any dose of study
        vaccine, and no other vaccinations may be planned for two weeks after each dose of study
        vaccine.

        Prior diagnosis of sexually transmitted infections (STIs), genital warts, or juvenile
        recurrent papillomatosis.

        History of any severe allergic reaction (e.g., swelling of the mouth and throat, difficulty
        breathing, hypotension, or shock) that required medical intervention.

        Known allergies to any vaccine component, including aluminum, yeast, or BENZONASE™
        (nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]).

        Previous treatment with any immune globulin preparation or blood-derived products within
        the six months prior to the first injection and none may be planned during the study.

        Known coagulation disorder that would contraindicate Intramuscular (IM) injections.

        Any clinically significant diseases (other than HIV infection) or clinically significant
        findings during the screening medical history or physical examination that, in the
        investigator's opinion, would compromise the outcome of this study.

        Breastfeeding.