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

NCT00339040 | Completed Phase 2 Results

• 3 other identifiers: P104710163PACTG P1047
• Study Type: interventional
• Target: 130
• Locations: 2 countries
• Sites: 34

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.

Conditions

HIV Infections; Sexually Transmitted Diseases

Keywords

HPV

Outcome Measures

Primary Outcomes (4)

• Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)

  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.

  Within 14 days of first three doses of vaccination

• Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment

  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".

  Within 14 days of first three doses of vaccination

• Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion

  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.

  At week 28 after beginning the vaccination series

• Serum Anti-HPV Antibody Titers (cLIA)

  Geometric means of Type-specific 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.

Secondary Outcomes (3)

• CD4 Count Over Time

  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

  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

  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.

Study Arms (2)

Arm A: QHPV

ACTIVE COMPARATOR

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)

Arm B: Placebo/QHPV

OTHER

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

Other: Placebo/QHPV

Interventions

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

QHPV at week 0, 8, 24 and 96.

Also known as: QHPV

Arm A: QHPV

Placebo/QHPV OTHER

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

Arm B: Placebo/QHPV

Eligibility Criteria

• Age: 7 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (34)

Usc La Nichd Crs

Alhambra, California, 91803, United States

Location

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, 90806, United States

Location

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

Los Angeles, California, 90095-1752, United States

Location

Children's Hosp. of Orange County

Orange, California, 92868-3874, United States

Location

UCSD Mother-Child-Adolescent Program CRS

San Diego, California, 92103, United States

Location

Univ. of California San Francisco NICHD CRS

San Francisco, California, 94143, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Med. Ctr.

Hartford, Connecticut, 06106, United States

Location

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

Washington D.C., District of Columbia, 20010, United States

Location

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20060, United States

Location

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, 33316, United States

Location

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, 33136, United States

Location

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

Chicago, Illinois, 60608, United States

Location

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Chicago Children's CRS

Chicago, Illinois, 60614, United States

Location

Children's Hosp.

New Orleans, Louisiana, 70118, United States

Location

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, 02118, United States

Location

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, 01605, United States

Location

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, 48201, United States

Location

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, 07103, United States

Location

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

Brooklyn, New York, 11203, United States

Location

Nyu Ny Nichd Crs

New York, New York, 10016, United States

Location

Strong Memorial Hospital Rochester NY NICHD CRS

Rochester, New York, 14642, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794-8111, United States

Location

Bronx-Lebanon CRS

The Bronx, New York, 10457, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

DUMC Ped. CRS

Durham, North Carolina, 27710, United States

Location

St. Jude/UTHSC CRS

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hosp. CRS

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital CRS

Seattle, Washington, 98105, United States

Location

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

San Juan, 00935, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Related Publications (6)

• 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.

  PMID: 15297048 BACKGROUND

• 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.

  PMID: 15246630 BACKGROUND

• 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.

  PMID: 15887427 BACKGROUND

• 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.

  PMID: 20574412 RESULT

• 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.

  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.

  RESULT

MeSH Terms

Conditions

HIV Infections; Sexually Transmitted Diseases

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Myron J. Levin, MD

  Pediatric Infectious Diseases Section, University of Colorado Health Sciences Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: June 20, 2006
• Study Start: October 1, 2006
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: November 5, 2021
• Results First Posted: January 16, 2012

Record last verified: 2019-01

Locations

PR (2); US (32)