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

NCT00798265 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 09002409-C-0024
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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 vaccines 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, human immunodeficiency virus (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.

Conditions

Human Immunodeficiency Virus; Human Papillomavirus- 6, 11, 16, 18; Adolescent; Papillomavirus Vaccines

Keywords

HPV Vaccination; HPV Immunogenicity; HIV Infection; HIV Negative; Adolescents and Young Adults; Healthy Volunteer; HV; Adolescent

Outcome Measures

Primary Outcomes (1)

• Immunogenicity of the Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine in Human Immunodeficiency Virus (HIV)-Infected Preadolescents, Adolescents and Young Adults 12-26 Years of Age

  Immunogenicity was measured by the vaccine-induced antibody response collectively for preadolescents, adolescents and young adults an reported per cohort for participants with HIV and without HIV. Participants' serum was used to check the level of human papillomavirus (HPV) neutralization antibody. Neutralizing antibody is an antibody that can bind to the infectious organism such as viruses and stop the spread of the disease. The antibody level was compared between the participants with HIV and without HIV.

  Up to 36 months

Secondary Outcomes (14)

• Human Papilloma Virus (HPV) Vaccine Immunogenicity Between Human Immunodeficiency Virus (HIV)-Infected Participants Receiving Highly Active Antiretroviral Therapy (HAART) & Those Not Receiving HAART With Similar T-lymphocytes (CD4) & Viral Load Parameters

  At study entry

• Number of Participants With Log Change in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels After Human Papilloma Virus (HPV) Vaccination

  Baseline, and months 1, 3, 7 and 12

• Fold Change in Anti-Human Papilloma Virus (HPV) Titer and T-lymphocytes (CD4) Count (Only at Baseline)

  Months 7, 12, 24 and 36

• T-lymphocytes (CD4) Count (Only at Baseline)

  Baseline

• Number of Participants With Human Papilloma Virus (HPV) Deoxyribonucleic Acid (DNA) Positivity by Oral/Buccal Swabs at Baseline in the Study Cohort Populations

  Baseline

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0)

  Date treatment consent signed to date off study, up to 43 months and 8 days

Study Arms (3)

Cohort 1 - 0.5 mL dose injected intramuscular (IM)

EXPERIMENTAL

0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0

Biological: Gardasil; Behavioral: Survey

Cohort 2 - 0.5 mL dose injected intramuscular (IM)

EXPERIMENTAL

0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0

Biological: Gardasil; Behavioral: Survey

Cohort 3 - 0.5 mL dose injected intramuscular (IM)

ACTIVE COMPARATOR

0.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months (+/- 2 weeks) and knowledge survey at week 0

Biological: Gardasil; Behavioral: Survey

Interventions

Gardasil BIOLOGICAL

.5 mL dose injected intramuscular (IM) at 0, 2 and 6 months

Also known as: Human Papillomavirus 9-valent Vaccine, Recombinant

Cohort 1 - 0.5 mL dose injected intramuscular (IM); Cohort 2 - 0.5 mL dose injected intramuscular (IM); Cohort 3 - 0.5 mL dose injected intramuscular (IM)

Survey BEHAVIORAL

Administration of online risk behavior and knowledge survey done at week 0.

Cohort 1 - 0.5 mL dose injected intramuscular (IM); Cohort 2 - 0.5 mL dose injected intramuscular (IM); Cohort 3 - 0.5 mL dose injected intramuscular (IM)

Eligibility Criteria

• Age: 12 Years - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 12 to 26 years
• Females and males
• Human immunodeficiency virus (HIV)-positive
• Cluster of differentiation 4 (CD4) cell count and Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) level parameters
• CD4 cell count greater than or equal to 350 cells/mm(3)
• HIV-1 RNA level by reverse transcription-polymerase chain reaction (RT PCR) less than or equal to 20,000 copies/ml
• On stable highly active antiretroviral therapy (HAART) regimen for greater than or equal to 6 months with CD4 and viral load parameters as outlined in 2.1.1.4
• 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.
• 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)
• Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

You may not qualify if:

• 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)
• Prothrombin time (PT) or partial thromboplastin time (PTT) greater than or equal to 1.5 times upper limits of normal (ULN) (with the exception of patients with known clotting disorders or known lupus anticoagulant).
• Any of the following hepatic abnormalities
• Alanine transaminase (ALT)/ serum glutamate-pyruvate transaminase (SGPT) and/or Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) greater than 2.5 times ULN
• Total bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.
• 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.
• Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.
• Chemotherapy for active cancer.
• Documented history of non-adherence to antiretroviral treatment regimen within 12 months of study entry.
• Pregnancy or breastfeeding.
• 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.
• Known immediate hypersensitivity to yeast or any of the vaccine components.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev. 1988;10:122-63. doi: 10.1093/oxfordjournals.epirev.a036020.

  PMID: 2852116 BACKGROUND

• Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6;348(6):518-27. doi: 10.1056/NEJMoa021641.

  PMID: 12571259 BACKGROUND

• Koshiol JE, Laurent SA, Pimenta JM. Rate and predictors of new genital warts claims and genital warts-related healthcare utilization among privately insured patients in the United States. Sex Transm Dis. 2004 Dec;31(12):748-52. doi: 10.1097/01.olq.0000145851.76025.ad.

  PMID: 15608590 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; Human Papillomavirus Recombinant Vaccine nonavalent; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Dr. Hoyoung Maeng
• Organization: National Cancer Institute

hoyoung.maeng@nih.gov

240-781-3253

Study Officials

• Hoyoung M Maeng, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 25, 2008
• First Posted: November 26, 2008
• Study Start: June 29, 2009
• Primary Completion: September 22, 2012
• Study Completion: February 4, 2013
• Last Updated: November 20, 2024
• Results First Posted: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)