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

Phase 2
Completed
Conditions
HIV Infections
Sexually Transmitted Diseases
Interventions
Biological: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)
Other: Placebo/QHPV
Registration Number
NCT00339040
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A: QHPVQuadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)QHPV at week 0, 8, 24, 96.
Arm B: Placebo/QHPVPlacebo/QHPVPlacebo at week 0, 8, 24; QHPV at week 96, 104, 120.
Primary Outcome Measures
NameTimeMethod
Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)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 TreatmentWithin 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 SeroconversionAt 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)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)

Secondary Outcome Measures
NameTimeMethod
HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over TimeArm 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 Count Over TimeArm 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 TimeArm 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.

Trial Locations

Locations (34)

St. Jude/UTHSC CRS

🇺🇸

Memphis, Tennessee, United States

Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS

🇵🇷

San Juan, Puerto Rico

San Juan City Hosp. PR NICHD CRS

🇵🇷

San Juan, Puerto Rico

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

🇺🇸

Los Angeles, California, United States

Rush Univ. Cook County Hosp. Chicago NICHD CRS

🇺🇸

Chicago, Illinois, United States

Chicago Children's CRS

🇺🇸

Chicago, Illinois, United States

Children's Hosp. of Boston NICHD CRS

🇺🇸

Boston, Massachusetts, United States

Texas Children's Hosp. CRS

🇺🇸

Houston, Texas, United States

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

🇺🇸

Miami, Florida, United States

UCSD Mother-Child-Adolescent Program CRS

🇺🇸

San Diego, California, United States

DUMC Ped. CRS

🇺🇸

Durham, North Carolina, United States

Univ. of California San Francisco NICHD CRS

🇺🇸

San Francisco, California, United States

Univ. of Colorado Denver NICHD CRS

🇺🇸

Aurora, Colorado, United States

Miller Children's Hosp. Long Beach CA NICHD CRS

🇺🇸

Long Beach, California, United States

Usc La Nichd Crs

🇺🇸

Alhambra, California, United States

Children's Hosp. of Orange County

🇺🇸

Orange, California, United States

Connecticut Children's Med. Ctr.

🇺🇸

Hartford, Connecticut, United States

Children's National Med. Ctr. Washington DC NICHD CRS

🇺🇸

Washington, District of Columbia, United States

Univ. of Florida Jacksonville NICHD CRS

🇺🇸

Jacksonville, Florida, United States

Howard Univ. Washington DC NICHD CRS

🇺🇸

Washington, District of Columbia, United States

South Florida CDTC Ft Lauderdale NICHD CRS

🇺🇸

Fort Lauderdale, Florida, United States

Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program

🇺🇸

Chicago, Illinois, United States

Boston Medical Center Ped. HIV Program NICHD CRS

🇺🇸

Boston, Massachusetts, United States

Children's Hospital of Michigan NICHD CRS

🇺🇸

Detroit, Michigan, United States

WNE Maternal Pediatric Adolescent AIDS CRS

🇺🇸

Worcester, Massachusetts, United States

Rutgers - New Jersey Medical School CRS

🇺🇸

Newark, New Jersey, United States

Strong Memorial Hospital Rochester NY NICHD CRS

🇺🇸

Rochester, New York, United States

Nyu Ny Nichd Crs

🇺🇸

New York, New York, United States

SUNY Stony Brook NICHD CRS

🇺🇸

Stony Brook, New York, United States

Seattle Children's Hospital CRS

🇺🇸

Seattle, Washington, United States

SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS

🇺🇸

Brooklyn, New York, United States

Children's Hosp.

🇺🇸

New Orleans, Louisiana, United States

Bronx-Lebanon CRS

🇺🇸

Bronx, New York, United States

Jacobi Med. Ctr. Bronx NICHD CRS

🇺🇸

Bronx, New York, United States

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