Safety of and Immune Response to a Novel Human Papillomavirus Vaccine in HIV Infected Children
|ClinicalTrials.gov Identifier: NCT00339040|
Recruitment Status : Completed
First Posted : June 20, 2006
Results First Posted : January 16, 2012
Last Update Posted : January 13, 2015
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections Sexually Transmitted Diseases||Biological: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV) Other: Placebo/QHPV||Phase 2|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||130 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||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|
|Study Start Date :||October 2006|
|Actual Primary Completion Date :||August 2009|
|Actual Study Completion Date :||August 2009|
Active Comparator: Arm A: QHPV
QHPV at week 0, 8, 24, 96.
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
Arm B: Placebo/QHPV
Placebo at week 0, 8, 24; QHPV at week 96, 104, 120.
Placebo at week 0, 8, 24 and QHPV at week 96, 104, 120.
- 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)
- 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. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00339040
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|Study Chair:||Myron J. Levin, MD||Pediatric Infectious Diseases Section, University of Colorado Health Sciences Center|