A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00798265
First received: November 25, 2008
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

Background:

  • Human papilloma virus (HPV) is a common sexually transmitted disease. There are more than 100 different HPV types, and both males and females can get HPV infection. Most people do not have any symptoms when they become infected and are able to get rid of the infection on their own. However, they can still become re-infected with the same or a different HPV type, and in some people HPV infection persists.
  • Persistent HPV infection is associated with the development of precancerous lesions and cancer. HPV types are classified as either high risk or low risk based on whether their persistence will lead to cancer.
  • Patients who have suppressed immune systems are at a higher risk for HPV-related complications. They are more likely to contract multiple HPV types and have more persistent infection that can lead to precancerous lesions or cancer, which are then difficult to treat and often recur.
  • A recently approved vaccine for HPV induces immunity to HPV 6, 11, 16, and 18. It was shown to be highly effective in preventing infection with these HPV types, and is approved for use in females 9 to 26 years of age. However, much less is known about the vaccine s ability to induce immunity in males or individuals with suppressed immune systems.

Objectives:

- To investigate whether the HPV vaccine is safe to give and able to induce immunity in both female and male adolescents and young adults with HIV infection compared to healthy, HIV-negative persons of the same age.

Eligibility:

- Males and females, 12 to 26 years of age, divided into three groups: (1) Healthy and HIV-negative, (2) HIV-positive and on antiretroviral therapy, and (3) HIV-positive and not on antiretroviral therapy.

Design:

  • Before beginning vaccination, participants will have a complete physical examination and blood drawn for routine blood tests, special tests of the immune system, antibody tests, and an HIV test.
  • HPV vaccine will be given by injection into the muscle at 0, 2, and 6 months, according to the standard vaccination schedule.
  • Patients with HIV infection will be monitored for a week following the first injection to test the level of HIV in the blood 3 days and 5 days after the first injection.
  • Participants will also be asked to fill out a 10- to 15-minute Web-based survey about awareness, health behaviors, and personal choices related to risk factors for HIV, HPV, and other sexually transmitted diseases. Participants are not required to fill out the survey to receive the vaccine.
  • The total duration of the study is 4 years. During the first year of the study, participants will return for six additional 1-day visits at months 1, 2, 3, 6, 7, and 12. Participants will return for 1-day visits every 6 months for the remaining 3 years.

Condition Intervention Phase
Human Immunodeficiency Virus
Human Papillomavirus- 6, 11, 16, 18
Adolescent
Papillomavirus Vaccines
Drug: GARDASIL (Quadrivalent HPV (Types 6,11, 16, 18)
Biological: Administration of 3 doses of quaddrivalent
Behavioral: Administration of an on line web-based risk
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents and Young Adults

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in antibody titers following quadrivalent HPV vaccination in HIV-infected subjects; Safety of quadrivalent HPV vaccination in HIV-infected subjects.

Secondary Outcome Measures:
  • Determine if there are differences in antibody titers between HIV-infected and HIV negative subjects following HPV vaccination; Determine if there are differences in antibody titers between HIV-infected subjects receiving HAART and subjects.

Enrollment: 26
Study Start Date: October 2008
Study Completion Date: February 2013
Intervention Details:
    Drug: GARDASIL (Quadrivalent HPV (Types 6,11, 16, 18)
    N/A
    Biological: Administration of 3 doses of quaddrivalent
    N/A
    Behavioral: Administration of an on line web-based risk
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years to 26 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • ELIGIBILITY CRITERIA:

Cohort 1 Inclusion and Exclusion Eligibility Criteria:

INCLUSION CRITERIA:

2.1.1.1 Age 12 to 26 years

2.1.1.2 Females and males

2.1.1.3 HIV-positive

2.1.1.4 CD4 cell count and HIV-1 RNA level parameters

  • CD4 cell count greater than or equal to 350 cells/mm(3)
  • HIV-1 RNA level by RT PCR less than or equal to 20,000 copies/ml

2.1.1.5 On stable HAART regimen for greater than or equal to 6 months with CD4 and viral load parameters as outlined in 2.1.1.4

2.1.1.6 Patients greater than or equal to 18 years willing to provide informed consent or parent/guardian willing to provide informed consent for minor children less than 18 years of age.

2.1.1.7 Informed assent for patients 12-17 years of age (Optional at the discretion of the Principal Investigator and Parent/Guardian based on maturity level of minor)

2.1.1.8 Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

EXCLUSION CRITERIA:

2.1.1.9 Any of the following hematologic abnormalities

  • Hemoglobin less than 10.0 g/dL
  • Neutrophil count less than 1500/mm(3)
  • Platelet count less than 75,000/mm(3)
  • PT or PTT greater than or equal to 1.5 times ULN (with the exception of patients with known clotting disorders or known lupus anticoagulant).

2.1.1.10 Any of the following hepatic abnormalities

  • ALT/SGPT and/or AST/SGOT greater than 2.5 times ULN
  • Total bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.

2.1.1.11 Positive tests (antibody and/or antigen) for hepatitis B and hepatitis C viruses, unless the result is consistent with prior vaccination or prior infection with full recovery.

2.1.1.12 Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.

2.1.1.13 Chemotherapy for active cancer.

2.1.1.14 Documented history of non-adherence to antiretroviral treatment regimen within 12 months of study entry.

2.1.1.15 Pregnancy or breastfeeding.

2.1.1.16 Use of immunosuppressive or immunomodulating agents within 8 weeks of study enrollment. Note: patients receiving oral corticosteroids for management of asthma or contact hypersensitivity for less than or equal to 14 days in duration will be allowed to enroll as long as it has been greater than or equal to 30 days since oral corticosteroid administration.

2.1.1.17 Known immediate hypersensitivity to yeast or any of the vaccine components.

2.1.1.18 Use of investigational agents within 4 weeks prior to study enrollment.

2.1.1.19 Active external genital warts requiring treatment or CIN2/3

2.1.1.20 Any clinically significant diseases (other than HIV infection) or findings during study screening that, in the opinion of the Principal Investigator or Lead Associate Investigator, may interfere with the study.

Cohort 2 Inclusion and Exclusion Eligibility Criteria:

Inclusion Criteria

2.1.2.1 Age 12 to 26 years

2.1.2.2 Females and males

2.1.2.3 HIV-positive

2.1.2.4 CD4 cell count and HIV-1 RNA level parameters

  • CD4 cell count greater than or equal to 500 cells/mm(3)
  • HIV-1 RNA level by RT PCR less than or equal to 20,000 copies/ml.

2.1.2.5 Not receiving antiretroviral treatment with CD4 and viral load parameters as outlined in 2.1.2.4.

2.1.2.6 Patients greater than or equal to 18 years willing to provide informed consent or parent/guardian willing to provide informed consent for minor children less than 18 years of age.

2.1.2.7 Informed assent for patients 12-17 years of age (Optional at the discretion of the Principal Investigator and Parent/Guardian based on maturity level of minor)

2.1.2.8 Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

EXCLUSION CRITERIA:

2.1.2.9 Any of the following hematologic abnormalities:

  • Hemoglobin less than 10.0 g/dL
  • Neutrophil count less than 1500/mm(3)
  • Platelet count less than 75,000/mm(3)
  • PT or PTT greater than or equal to 1.5 times ULN (with the exception of patients with known clotting disorders or known lupus anticoagulant).

2.1.2.10 Any of the following hepatic abnormalities

  • ALT/SGPT and/or AST/SGOT greater than 2.5 times ULN
  • Total bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.

2.1.2.11 Positive tests (antibody and/or antigen) for hepatitis B and hepatitis C viruses, unless the result is consistent with prior vaccination or prior infection with full recovery.

2.1.2.12 Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.

2.1.2.13 Chemotherapy for active cancer.

2.1.2.14 Pregnancy or breastfeeding.

2.1.2.15 Use of immunosuppressive or immunomodulating agents within 8 weeks prior to study enrollment. Note: patients receiving oral corticosteroids for management of asthma or contact hypersensitivity for less than or equal to 14 days in duration will be allowed to enroll as long as it has been greater than or equal to 30 days since oral corticosteroid administration.

2.1.2.16 Known immediate hypersensitivity to yeast or any of the vaccine components.

2.1.2.17 Use of investigational agents within 4 weeks prior to study enrollment.

2.1.2.18 Active external genital warts requiring treatment or CIN2/3

2.1.2.19 Any clinically significant diseases (other than HIV infection) or findings during study screening that, in the opinion of the Principal Investigator or Lead Associate Investigator may interfere with the study.

Cohort 3 Inclusion and Exclusion Eligibility Criteria:

INCLUSION CRITERIA:

2.1.3.1 Age 12 to 26 years

2.1.3.2 Females and males

2.1.3.3 HIV-negative

2.1.3.4 Patients greater than or equal to 18 years willing to provide informed consent or parent/guardian willing to provide informed consent for minor children less than 18 years of age.

2.1.3.5 Informed assent for patients 12-17 years of age (Optional at the discretion of the Principal Investigator and Parent/Guardian based on maturity level of minor)

2.1.3.6 Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

EXCLUSION CRITERIA:

2.1.3.7 Any of the following hematologic abnormalities:

  • Hemoglobin less than 10.0 g/dL
  • Neutrophil count less than 1500/mm(3)
  • Platelet count less than 75,000/mm(3)
  • PT or PTT greater than or equal to 1.5 times ULN (with the exception of patients with known clotting disorders or known lupus anticoagulant).

2.1.3.8 Any of the following hepatic abnormalities

  • ALT/SGPT and/or AST/SGOT greater than 2.5 times ULN
  • Total Bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.

2.1.3.9 Positive tests (antibody and/or antigen) for HIV, hepatitis B and hepatitis C viruses, unless the result is consistent with prior vaccination or prior infection with full recovery.

2.1.3.10 Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.

2.1.3.11 Chemotherapy for active cancer.

2.1.3.12 Pregnancy or breastfeeding

2.1.3.13 Use of immunosuppressive or immunomodulating agents within 8 weeks prior to study enrollment. Note: patients receiving oral corticosteroids for management of asthma or contact hypersensitivity for less than or equal to 14 days in duration will be allowed to enroll as long as it has been greater than or equal to 30 days since oral corticosteroid administration.

2.1.3.14 Known immediate hypersensitivity to yeast or any of the vaccine components.

2.1.3.15 Use of investigational agents within 4 weeks prior to study enrollment.

2.1.3.16 Active external genital warts requiring treatment or CIN2/3

2.1.3.17 Any clinically significant diseases or findings during study screening that, in the opinion of the Principal Investigator or Lead Associate Investigator may interfere with the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00798265

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Lauren V Wood, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00798265     History of Changes
Other Study ID Numbers: 090024, 09-C-0024
Study First Received: November 25, 2008
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
HPV Vaccination
HPV Immunogenicity
HIV Infection
HIV Negative
Adolescents and Young Adults
Healthy Volunteer
HV
Adolescent

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on October 01, 2014