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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01512784
• Other study ID #: HLS04/2011
• Status: Recruiting
• Phase: Phase 3
• First received: January 13, 2012
• Last updated: January 18, 2012
• Start date: October 2011
• Est. completion date: July 2013

Study information

• Verified date: January 2012
• Source: University of Milan
• Contact: Gian Vincenzo Zuccotti, Head Paediatric Department
• Phone: 0039/02/39042253
• Email: gianvincenzo.zuccotti[@]unimi.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 13 Years to 27 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV
• HPV

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Luigi Sacco Hospital , Department of Paediatrics, via G.B Grassi, 74	Milan

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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.	No
Secondary	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).	No