Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety of and Immune Response to a Novel Human Papillomavirus Vaccine in HIV Infected Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00339040
Recruitment Status : Completed
First Posted : June 20, 2006
Results First Posted : January 16, 2012
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE June 19, 2006
First Posted Date  ICMJE June 20, 2006
Results First Submitted Date  ICMJE September 7, 2011
Results First Posted Date  ICMJE January 16, 2012
Last Update Posted Date February 15, 2019
Study Start Date  ICMJE October 2006
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2011)
  • Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) [ Time Frame: Within 14 days of first three doses of vaccination ]
    Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). The grades used are: Grade 1="Mild", Grade 2="Moderate", Grade 3="Severe", Grade 4="Potentially Life-Threatening". All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
  • Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment [ Time Frame: Within 14 days of first three doses of vaccination ]
    Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). All grade 3 and higher signs, symptoms, and laboratory toxicities attributed to study treatment were included. The relationship between the Adverse Events and the vaccination were evaluated by study team and assigned to, for example, "Treatment related", "Non-treatment related", "Baseline", "Possibly treatment related".
  • Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion [ Time Frame: At week 28 after beginning the vaccination series ]
    Serum anti-HPV 6, 11, 16, and 18 antibody was measured using a competitive Luminex immunoassay (cLIA; reported in milli-Merck Units [mMU]/mL). Sero-positivity was defined as an anti-HPV titer ≥20, 16, 20, and 24 mMU/mL, for HPV types 6, 11, 16, and 18, respectively.
  • Serum Anti-HPV Antibody Titers (cLIA) [ Time Frame: Arm A week 0, 28, 72, 96, 97, 100; Arm B week 0, 28, 72, 96, 97, 100, 124. ]
    Geometric means of Type-specific Serum anti-HPV antibody titers (cLIA)
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2006)
  • Safety, as determined by development of Grade 3 or 4 adverse events (AEs)
  • safety, as determined by development of Grade 3 or 4 AEs attributed to study treatment
  • immunogenicity, as determined by anti-HPV 6, 11, 16, 18 responses measured by Clinical Laboratory Improvement Act (CLIA) at Week 28
  • serum antibody titers
Change History Complete list of historical versions of study NCT00339040 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2011)
  • CD4 Count Over Time [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]
  • CD4 Percent Over Time [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]
  • HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2006)
  • Change in CD4 count and percent
  • change in viral load (HIV-1 RNA copies/ml)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of and Immune Response to a Novel Human Papillomavirus Vaccine in HIV Infected Children
Official Title  ICMJE Phase II Safety and Immunogenicity Study of Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine in HIV Infected Children 7 to 12 Years of Age
Brief 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.
Detailed Description

Genital HPV infection is the most common sexually transmitted infection in the world and may lead to genital warts, anogenital dysplasias, and invasive cancers. HIV infected people and others with compromised immunity are at greater risk for HPV-related complications. In particular, researchers are concerned about the risk of HPV infection to women, who may be infected by their male partners, especially if these partners engage in anal intercourse. HIV infected women tend to have multiple types of HPV (associated with a greater risk of HPV-related disease), are less likely to clear HPV-related conditions, and are more likely to progress to HPV-related disease. The quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine to be tested in this study was safe and generally well tolerated in previous studies conducted in healthy and HPV-exposed adolescents, young adults, and older women. However, it is still unclear if the vaccine will be safe and will elicit a similar immune response in younger children. The purpose of this study is to evaluate the safety and immunogenicity of the novel quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine in HIV infected children 7 to 12 years of age.

This study had two stages and lasted at least 108 weeks. In Stage I, participants were stratified by CD4 percentage (CD4%) nadir and CD4% at study screening (Stratum A: CD4% Nadir < 15 and CD4% ≥ 15 at screening, Stratum B: CD4% Nadir ≥ 15 and < 25 and CD4% ≥ 15 at screening, Stratum C: CD4% Nadir ≥ 25 and CD4% ≥ 25 at screening). Within each stratification group, they were randomly assigned to one of two arms. During Stage I, Arm A (QHPV:Quadrivalent human papillomavirus vaccine) participants received 3 doses of vaccine, while Arm B (Placebo/QHPV) participants received 3 doses of placebo. Participants did not know whether they were receiving vaccine or placebo. Participants received their assigned intervention at study entry and Weeks 8 and 24. At Week 96, Stage II began, and all study participants were told if they received vaccine or placebo in Stage I. Arm A participants received an additional dose of vaccine at Week 96; Arm B participants received doses of vaccine at Weeks 96, 104, and 120. Over the course of the study, there were at least 12 study visits. A physical exam and blood collection occurred at most visits; medical history occurred at selected visits.

After each vaccination, participants were observed for at least 30 minutes to monitor for any allergic reactions possibly resulting from the vaccination. For 15 days following vaccination, parents or guardians were asked to complete a "report card" with details of each child's signs and symptoms. Three days after each vaccination, parents or guardians of study participants were contacted by telephone and asked about any adverse events that a child may have experienced.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • HIV Infections
  • Sexually Transmitted Diseases
Intervention  ICMJE
  • Biological: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)
    QHPV at week 0, 8, 24 and 96.
    Other Name: QHPV
  • Other: Placebo/QHPV
    Placebo at week 0, 8, 24 and QHPV at week 96, 104, 120.
Study Arms  ICMJE
  • Active Comparator: Arm A: QHPV
    QHPV at week 0, 8, 24, 96.
    Intervention: Biological: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)
  • Arm B: Placebo/QHPV
    Placebo at week 0, 8, 24; QHPV at week 96, 104, 120.
    Intervention: Other: Placebo/QHPV
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 12, 2011)
130
Original Enrollment  ICMJE
 (submitted: June 19, 2006)
120
Actual Study Completion Date  ICMJE August 2009
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00339040
Other Study ID Numbers  ICMJE P1047
10163 ( Registry Identifier: DAIDS ES Registry Number )
PACTG P1047
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Study Chair: Myron J. Levin, MD Pediatric Infectious Diseases Section, University of Colorado Health Sciences Center
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP