Long Term Immunogenicity of Quadrivalent Human Papillomavirus Vaccine (Gardasil®)in HIV-infected Adolescents and Young Adults

Long Term Immunogenicity of Quadrivalent Human Papillomavirus Vaccine (Gardasil®)in HIV-infected Adolescents and Young Adults vs. Healthy Adolescents and Young Adults: Non-randomized Controlled Clinical Trial

Infection with human immunodeficiency virus (HIV) is an important risk factor for HPV infection and the development of HPV-associated lesions in female and male anogenital tract. Data on safety and immunogenicity of quadrivalent human papillomavirus vaccine in HIV-infected population are few. The present study is a non-randomized controlled clinical trial with the primary objective to determine safety ad immunogenicity of quadrivalent human papillomavirus vaccine (Gardasil®) in HIV-infected female and male adolescents and young adults.

Study Overview

• Status: Unknown
• Conditions: HIV; HPV
• Intervention / Treatment: Biological: Quadrivalent Human Papillomavirus (6, 11, 16 and 18) vaccine (Gardasil ®); Biological: Quadrivalent Human Papillomavirus (6, 11, 16 and 18) vaccine (Gardasil ®)

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20157
    • Recruiting
    • Luigi Sacco Hospital , Department of Paediatrics, via G.B Grassi, 74
    • Contact: Francesca Penagini, Doctor; Phone Number: 0039/02/39042234; Email: frapenagini@tiscali.it
    • Sub-Investigator: Alessandra Viganò, Paediatrician
    • Sub-Investigator: Francesca Di Nello, Doctor
    • Sub-Investigator: Vania Giacomet, Paediatrician
    • Principal Investigator: Gian Vincenzo Zuccotti, Full Professor
    • Sub-Investigator: Paola Erba, Paediatrician
    • Sub-Investigator: Valeria Manfredini, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 27 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For both HIV-infected and healthy subjects:

  • Subjects aged 13-27 years, females and males
  • Written informed consent from parent or guardian if applicable (age<18 years)

• For HIV-infected subjects:

  • HIV-positive
  • Asymptomatic subjects (generalized lymphadenopathy is accepted)
  • Lymphocyte CD4+ count > or equal to 350 cells/mm3

• For subjects receiving HAART:

  • Good compliance to therapy
  • At least two suppressed viral loads HIV-RNA (<37copies/ml9 during 6 months prior to enrollment.

Exclusion Criteria:

• For female subjects (both HIV-infected and healthy)
• Pregnancy or breastfeeding
• Total hysterectomy. Participants who have undergone partial hysterectomy and have a cervix are not excluded.
• For both females and males (HIV-infected and healthy):
• Prior vaccination with quadrivalent HPV vaccine Gardasil before study entry.
• History of severe allergic reaction after previous vaccination or hypersensitivity to any vaccine component.
• Any serious chronic or progressive disease (other than HIV) according to the judgment of the investigator:
• Acute infection requiring therapy or fever at time of enrollment
• Chronic autoimmune or oncologic disease receiving chemotherapy
• Concomitant therapies (other than HAART):
• Chronic therapy (for more than 14 days consecutively) with immunosuppressive or immunomodulating agents or chemotherapy during the 6 months prior to study entry.
• Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation prior to study entry.
• Use of investigational agents within 4 weeks prior to study enrollment.
• Current drug or alcohol use or dependence.
• Documented history of non-adherence to antiretroviral treatment regimen within 12 months prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV-infected adolescents and young adults; female and male HIV-infected subjects aged from 13-27 years old	Biological: Quadrivalent Human Papillomavirus (6, 11, 16 and 18) vaccine (Gardasil ®); Human Papillomavirus vaccine (types 6, 11, 16 and 18) (Recombinant, adsorbed). Each dose of Gardasil suspension for injection contains 0,5 ml. The shot is usually given in the arm muscle, 3 shots are given on the following schedule: First dose: at chosen date. Second dose: 2 months after dose 1. Third dose: 6 months after dose 1. Ingredients: highly purified non-infectious protein for each of the Human Papillomavirus types (6, 11, 16 and 18). Each dose (0,5ml) contains approximately: Human Papillomavirus type 6 L1 protein 20 micrograms. Human Papillomavirus type 11 L1 protein 40 micrograms. Human Papillomavirus type 16 L1 protein 40 micrograms. Human Papillomavirus type 18 L1 protein 20 micrograms.; Biological: Quadrivalent Human Papillomavirus (6, 11, 16 and 18) vaccine (Gardasil ®); Human Papillomavirus vaccine (types 6, 11, 16 and 18) (Recombinant, adsorbed). Each dose of Gardasil suspension for injection contains 0,5 ml. The shot is usually given in the arm muscle, 3 shots are given on the following schedule: first dose: at chosen date. Second dose: 2 months after dose 1. Third dose: 6 months after dose 1. Ingredients: highly purified non-infectious protein for each of the Human Papillomavirus types (6, 11, 16 and 18). Each dose (0,5ml) contains approximately: Human Papillomavirus type 6 L1 protein 20 micrograms. Human Papillomavirus type 11 L1 protein 40 micrograms. Human Papillomavirus type 16 L1 protein 40 micrograms. Human Papillomavirus type 18 L1 protein 20 micrograms.
Active Comparator: healthy adolescents and young adults; female and male healthy adolescents and young adults aged 13-27 years	Biological: Quadrivalent Human Papillomavirus (6, 11, 16 and 18) vaccine (Gardasil ®); Human Papillomavirus vaccine (types 6, 11, 16 and 18) (Recombinant, adsorbed). Each dose of Gardasil suspension for injection contains 0,5 ml. The shot is usually given in the arm muscle, 3 shots are given on the following schedule: First dose: at chosen date. Second dose: 2 months after dose 1. Third dose: 6 months after dose 1. Ingredients: highly purified non-infectious protein for each of the Human Papillomavirus types (6, 11, 16 and 18). Each dose (0,5ml) contains approximately: Human Papillomavirus type 6 L1 protein 20 micrograms. Human Papillomavirus type 11 L1 protein 40 micrograms. Human Papillomavirus type 16 L1 protein 40 micrograms. Human Papillomavirus type 18 L1 protein 20 micrograms.; Biological: Quadrivalent Human Papillomavirus (6, 11, 16 and 18) vaccine (Gardasil ®); Human Papillomavirus vaccine (types 6, 11, 16 and 18) (Recombinant, adsorbed). Each dose of Gardasil suspension for injection contains 0,5 ml. The shot is usually given in the arm muscle, 3 shots are given on the following schedule: first dose: at chosen date. Second dose: 2 months after dose 1. Third dose: 6 months after dose 1. Ingredients: highly purified non-infectious protein for each of the Human Papillomavirus types (6, 11, 16 and 18). Each dose (0,5ml) contains approximately: Human Papillomavirus type 6 L1 protein 20 micrograms. Human Papillomavirus type 11 L1 protein 40 micrograms. Human Papillomavirus type 16 L1 protein 40 micrograms. Human Papillomavirus type 18 L1 protein 20 micrograms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
type specific antibody titers for HPV types 6, 11, 16 and 18 at one month after completion of HPV vaccine series (T3) in HIV infected subjects vs. healthy subjects	Immunogenicity of quadrivalent human papillomavirus vaccine (Gardasil®) will be assessed by evaluation of type-specific antibody development for HPV types 6, 11, 16 and 18 from seronegative status at baseline (T0) to seropositive status at one month after the completion of HPV vaccine series (T3), compared with the same immunogenicity testings performed in healthy subjects matched for sex and age.	one month +/- 10 days after 3° vaccine dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antibody HPV titers to types 6, 11, 16 and 18, one month after the first two vaccination series (T1 and T2) in HIV-infected subjects vs healthy subjects	Antibody titers for HPV types 6, 11, 16 and 18 will be evaluated one month after the first (T1) and second (T2) vaccination dose in HIV-infected adolescents and young adults compared with the same immunological testings in healthy adolescents and young adults.	one month +/- 10 days after 1°vaccine dose and month+/- 10 days after 2° vaccine dose
antibody titers to HPV types 6, 11, 16 and 18 at month 12(T4)and 18 (T5)from baseline (T0).	To assess long-term immunogenicity of quadrivalent human papillomavirus vaccine (Gardasil® in HIV-infected and healthy subjects by evaluation of persistence of HPV antibody titers to types 6, 11, 16 and 18 at month 12 (T4) and 18(T5) from baseline (T0).	12 months +/- 10 days and 18 months +/-10 days from baseline
local and systemic adverse events	Safety and tolerability of three doses of quadrivalent human papillomavirus vaccine (Gardasil ®) in HIV-infected and healthy subjects will be assessed by evaluating the occurrence and severity of local and systemic adverse events during the 7 days after each vaccination dose.	7 days after each vaccination dose
HIV viral load and lymphocyte CD4+ count	Longitudinal monitoring of HIV-viral load and lymphocyte CD4+ count will be conducted in HIV-infected subjects from baseline (T0), throughout the study: one month after each vaccination dose (T1, T2, T3) and at month 12 and 18 from baseline (T4, T5).	baseline (T0), one month after each vaccination dose (T1, T2 and T3) and at month 12 (T4) and 18 (T5) from baseline.
lymphoproliferative responses, cytokine production and immunophenotype analysis of lymphocyte subpopulations	To evaluate in a subgroup of subjects (20 HIV-infected and 20 healthy) the following immunological parameters at baseline and at 1 month after 1° vaccination dose (T1) and at 1 month after 3° vaccination dose (T3): lymphoproliferative responses to HPV-16 L1 from PBMCs in peripheral blood Immunophenotype analysis of lymphocyte subpopulations in peripheral blood Cytokine production from peripheral lymphocyte subpopulations at baseline and after stimulation with HPV-16 recombinant protein L1.	baseline (T0), one month after 1° vaccination dose (T1) and one month after 3° vaccination dose (T3).

Collaborators and Investigators

• Sponsor: University of Milan
• Investigators: Principal Investigator: Gian Vincenzo Zuccotti, Head of Paediatric Department, L.Sacco Hospital, via G.B Grassi, 74 20157 Milano, Italy

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): July 1, 2013
• Study Completion (Anticipated): July 1, 2013

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 18, 2012
• First Posted (Estimate): January 19, 2012

Study Record Updates

• Last Update Posted (Estimate): January 19, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: HIV infection; Quadrivalent Human Papillomavirus Vaccine (HPV) Gardasil; Evaluation of quadrivalent HPV vaccine in adolescents and young adults.
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: HLS04/2011