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

NCT ID: NCT00339040

Last Updated: 2021-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2009-08-31

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.

Conditions

HIV Infections; Sexually Transmitted Diseases

Keywords

HPV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm A: QHPV

QHPV at week 0, 8, 24, 96.

Group Type: ACTIVE_COMPARATOR

Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)

Intervention Type: BIOLOGICAL

QHPV at week 0, 8, 24 and 96.

Arm B: Placebo/QHPV

Placebo at week 0, 8, 24; QHPV at week 96, 104, 120.

Group Type: OTHER

Placebo/QHPV

Intervention Type: OTHER

Placebo at week 0, 8, 24 and QHPV at week 96, 104, 120.

Interventions

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.

Intervention Type: BIOLOGICAL

Placebo/QHPV

Placebo at week 0, 8, 24 and QHPV at week 96, 104, 120.

Intervention Type: OTHER

Other Intervention Names

QHPV

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.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Myron J. Levin, MD

Role: STUDY_CHAIR

Pediatric Infectious Diseases Section, University of Colorado Health Sciences Center

Locations

Usc La Nichd Crs

Alhambra, California, United States

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States

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

Los Angeles, California, United States

Children's Hosp. of Orange County

Orange, California, United States

UCSD Mother-Child-Adolescent Program CRS

San Diego, California, United States

Univ. of California San Francisco NICHD CRS

San Francisco, California, United States

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States

Connecticut Children's Med. Ctr.

Hartford, Connecticut, United States

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

Washington D.C., District of Columbia, United States

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, United States

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, United States

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, United States

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, United States

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

Chicago, Illinois, 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.

New Orleans, Louisiana, United States

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, United States

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, United States

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, United States

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, United States

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

Brooklyn, New York, United States

Nyu Ny Nichd Crs

New York, New York, United States

Strong Memorial Hospital Rochester NY NICHD CRS

Rochester, New York, United States

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States

Bronx-Lebanon CRS

The Bronx, New York, United States

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, United States

DUMC Ped. CRS

Durham, North Carolina, United States

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Texas Children's Hosp. CRS

Houston, Texas, United States

Seattle Children's Hospital CRS

Seattle, Washington, 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

Countries

United States; Puerto Rico

References

Ault KA, Giuliano AR, Edwards RP, Tamms G, Kim LL, Smith JF, Jansen KU, Allende M, Taddeo FJ, Skulsky D, Barr E. A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine. Vaccine. 2004 Aug 13;22(23-24):3004-7. doi: 10.1016/j.vaccine.2004.02.020.

Reference Type: BACKGROUND

PMID: 15297048 (View on PubMed)

Brown DR, Fife KH, Wheeler CM, Koutsky LA, Lupinacci LM, Railkar R, Suhr G, Barr E, Dicello A, Li W, Smith JF, Tadesse A, Jansen KU. Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like particle vaccine. Vaccine. 2004 Jul 29;22(21-22):2936-42. doi: 10.1016/j.vaccine.2003.11.059.

Reference Type: BACKGROUND

PMID: 15246630 (View on PubMed)

Poland GA, Jacobson RM, Koutsky LA, Tamms GM, Railkar R, Smith JF, Bryan JT, Cavanaugh PF Jr, Jansen KU, Barr E. Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16: a 2-year randomized controlled clinical trial. Mayo Clin Proc. 2005 May;80(5):601-10. doi: 10.4065/80.5.601.

Reference Type: BACKGROUND

PMID: 15887427 (View on PubMed)

Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer WA 3rd, Read JS, Handelsman EL, Nowak B, Sattler CA, Saah A, Radley DR, Esser MT, Weinberg A; IMPAACT P1047 Protocol Team. Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J Acquir Immune Defic Syndr. 2010 Oct;55(2):197-204. doi: 10.1097/QAI.0b013e3181de8d26.

Reference Type: RESULT

PMID: 20574412 (View on PubMed)

P1047 ORAL PRESENTATION at the 25th International Papillomavirus Conference May 8-14 2009, Malmö, Sweden given by Anna Barbara Moscicki. Safety and immunogenicity of Gardasil® in HIV-infected children. Moscicki AB, Weinberg A, Song LY, Handelsman E, Patterson J, Saah A, Radley D, Read JS, Sattler C and Levin MJ for IMPAACT P1047 team.

Reference Type: RESULT

Weinberg A, Song LY, Handelsman E, Moscicki AB, Patterson J, Saah A, Radley D, Esser M, Read J, and Levin MJ for IMPAACT P1047 Team. The P1047 data up to week 28 have been analyzed and presented to 15th CROI as abstract and poster #619a: Safety and Immunogenicity of a Quadrivalent Vaccine to Prevent Human Papilloma Virus (HPV) in HIV-Infected Children: IMPAACT P1047.

Reference Type: RESULT

Other Identifiers

10163

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG P1047

Identifier Type: -

Identifier Source: secondary_id

P1047

Identifier Type: -

Identifier Source: org_study_id