Evaluation of Safety and Immunogenicity of a Human Papillomavirus (HPV) Vaccine in Human Immunodeficiency Virus (HIV) Infected Females - Full Text View

Purpose

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This Phase IV, observer-blind study is designed to evaluate the safety and immunogenicity of Cervarix™ in HIV infected females aged 15 to 25 years as compared to Merck's HPV vaccine (Gardasil®). For comparative purposes, a group of HIV negative females will also be evaluated. All subjects will receive the HPV vaccine (either Cervarix™ or Gardasil®) according to a three-dose schedule (Day 0, Week 6, Month 6).

Condition	Intervention	Phase
Human Papillomavirus Infection	Biological: GSK Biologicals' HPV vaccine 580299 Biological: Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Safety and Immunogenicity of Cervarix™ in Human Immunodeficiency Virus Infected Females

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Cancer HIV/AIDS HIV/AIDS and Pregnancy

Drug Information available for: Human papillomavirus vaccine, L1 type 16, 18 Human Papillomaviruses

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Occurrence and intensity of solicited local symptoms in HIV+ subjects. [ Time Frame: During the 7-day (Days 0 - 6) follow-up period after each vaccination ] [ Designated as safety issue: No ]
Occurrence, intensity and relationship to vaccination of solicited general symptoms in HIV+ subjects. [ Time Frame: During the 7-day (Days 0 - 6) follow-up period after each vaccination ] [ Designated as safety issue: No ]
Occurrence, intensity and relationship to vaccination of unsolicited symptoms in HIV+ subjects [ Time Frame: During the 30-day (Days 0 - 29) follow-up period after each vaccination ] [ Designated as safety issue: No ]
Occurrence of SAEs in HIV+ subjects. [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
Occurrence of medically significant conditions (including potential immune mediated diseases pIMDs) in HIV+ subjects. [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
Occurrence and outcome of pregnancies in HIV+ subjects. [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
Occurrence of clinically relevant abnormalities in hematological and biochemical parameters in HIV+ subjects. [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
CD4 cell count in HIV+ subjects [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
HIV viral load in HIV+ subjects [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
HIV clinical staging in HIV+ subjects [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
HPV-16 and HPV-18 antibody titers by Pseudovirion-Based Neutralization Assay (PBNA) in HIV+ subjects [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Occurrence and intensity of solicited local symptoms in HIV- subjects. [ Time Frame: During the 7-day (Days 0 - 6) follow-up period after each vaccination ] [ Designated as safety issue: No ]
Occurrence, intensity and relationship to vaccination of solicited general symptoms in HIV- subjects. [ Time Frame: During the 7-day (Days 0 - 6) follow-up period after each vaccination ] [ Designated as safety issue: No ]
Occurrence, intensity and relationship to vaccination of unsolicited symptoms in HIV- subjects. [ Time Frame: During the 30-day (Days 0 - 29) follow-up period after each vaccination ] [ Designated as safety issue: No ]
Occurrence of SAEs in HIV- subjects. [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
Occurrence of medically significant conditions (including pIMDs) in HIV- subjects. [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
Occurrence and outcome of pregnancies in all subjects. [ Time Frame: Throughout the entire study (up to Month 24) ] [ Designated as safety issue: No ]
Occurrence of clinically relevant abnormalities in hematological and biochemical parameters in all subjects. [ Time Frame: At Months 12, 18 and 24 ] [ Designated as safety issue: No ]
Occurrence of SAEs in all subjects. [ Time Frame: Throughout the entire study (up to Month 24) ] [ Designated as safety issue: No ]
Occurrence of medically significant conditions (including pIMDs) in all subjects. [ Time Frame: Up to 12 months after the last vaccine dose (up to Month 18) ] [ Designated as safety issue: No ]
CD4 cell count, HIV viral load and HIV clinical staging in HIV+ subjects. [ Time Frame: At Months 12, 18 and 24 ] [ Designated as safety issue: No ]
HPV-16 and HPV-18 antibody titers by Pseudovirion-Based Neutralization Assay (PBNA) in HIV- subjects [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
HPV-16 and HPV-18 antibody titers and total Immunoglobulin G (IgG) titers by Enzyme-Linked ImmunoSorbent Assay in serum in all subjects [ Time Frame: At Day 0, Week 6, Week 10, Months 7, 12, 18 and 24 ] [ Designated as safety issue: No ]
HPV-16 and HPV-18 antibody titers and total Immunoglobulin G (IgG) titers by Enzyme-Linked ImmunoSorbent Assay in cervicovaginal secretion (CVS) in post-menarcheal subjects who volunteer for this procedure [ Time Frame: At Day 0, Week 6, Week 10, Months 7, 12 and 24 ] [ Designated as safety issue: No ]
Frequencies of HPV-16 and HPV-18 specific B cells and T cells in subset of approximately 100 subjects (50 HIV+ and 50 HIV-) [ Time Frame: At Day 0, Week 6, Week 10, Months 7 and 12 ] [ Designated as safety issue: No ]

Estimated Enrollment:	600
Study Start Date:	October 2010
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group Cervarix	Biological: GSK Biologicals' HPV vaccine 580299 Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule. Other Name: Cervarix™
Active Comparator: Group Gardasil	Biological: Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule. Other Name: Gardasil®

Detailed Description:

This Protocol Posting has been updated following Protocol Amendment 2, December 2010, leading to:

The update of 1 Primary Outcome measure
The removal of 2 Primary Outcome measures
The update of 2 Secondary Outcome measures
The removal of 4 Secondary Outcome measures
The update of the timeframe of 1 of the updated Secondary outcome measures

Eligibility

Ages Eligible for Study:	15 Years to 25 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects who the investigator believes that they and/or their parent(s)/legally acceptable representative(s) (LAR) can and will comply with the requirements of the protocol.
A female between, and including, 15 and 25 years of age at the time of the first vaccination.
Written informed consent obtained from the subject and/or from the subject's parent or LAR.
Subjects willing to undergo HIV Voluntary Counseling and Testing (VCT) and willing to be informed of their HIV infection status.
For HIV seropositive subjects:
Subjects must be HIV seropositive according to World Health Organization (WHO) case definition.
Subject must be asymptomatic (or only have persistent generalized lymphadenopathy.)
Subjects should have a CD4 cell count > 350 cells/mm3.
If currently on antiretroviral therapy (ART), subjects must be compliant to triple therapy (highly active ART) and have undetectable viral load on two previous clinical visits within the six months prior to study entry.
For HIV seronegative subjects:
Subjects confirmed as HIV seronegative at the screening visit.
For non-virgin female subjects:
Subjects must have no history of abnormal cytology or CIN 1/2/3.
Subjects must have had no more than six life-time sexual partners prior to enrollment.
Subjects must have no history of congenital malformations of the uterine cervix, or history of cauterization or surgical procedures involving damage to the transformation zone of the cervix or stenosis.
Female subjects of non-childbearing potential may be enrolled in the study.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test at screening and on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.

Exclusion Criteria:

Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (Day 0 to Month 24).
ART not compliant with the National Guidelines.
Active tuberculosis (TB).
Current TB therapy.
Hemoglobin < 8.0 g/dL at the screening visit.
Creatinine > 1.5-fold the upper limit of normal (ULN) at the screening visit.
Alanine aminotransferase (ALT) > 2.5-fold ULN at the screening visit.
Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period (Day 0 to Month 24).
Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs (with the exception of ART) within six months prior to the first vaccine dose.
Administration of a vaccine not foreseen by the study protocol within 30 days (Days 0 - 29) before the first dose of study vaccine/control. Enrollment will be postponed until the subject is outside the specified window.
Planned administration of a vaccine not foreseen by the study protocol within 30 days before or 30 days after (i.e., Days 0 - 29) any dose of study vaccine.
Previous administration of components of the investigational vaccine.
Cancer or autoimmune disease under treatment.
Hypersensitivity to latex.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine/control.
Acute disease and/or fever at the time of enrollment.
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory testing performed at the screening visit.
History of any neurological disorders or seizures.
Pregnant or breastfeeding female.
A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose (i.e., up to Month 8).
Concurrently participating in another clinical study, at any time during the study period (Day 0 to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product.
Any medically diagnosed or suspected immunodeficient condition (other than HIV for HIV seropositive subjects), based on medical history, physical examination and/or laboratory tests results.
Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine/control or planned administration during the study period. Enrollment will be postponed until the subject is outside the specified window.
Administration of trimethoprim/sulphamethoxazole within seven days before the first dose of study vaccine/control, or planned administration of trimethoprim/sulphamethoxazole within seven days after the first dose of study vaccine/control.
Current drugs or alcohol abuse.
Child in care.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031069

Contacts

Contact: US GSK Clinical Trials Call Center

877-379-3718

GSKClinicalSupportHD@gsk.com

Locations

Brazil
GSK Investigational Site	Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
Ribeirão Preto, São Paulo, Brazil, 14049-900
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Campinas, Brazil, 13083-970
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
São Paulo, Brazil, 03015000
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
India
GSK Investigational Site	Recruiting
Chennai, India, 600113
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Kolkata, India, 700026
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Mumbai, India, 400014
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Pune, India, 411001
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
Vellore, India, 600116
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
Thailand
GSK Investigational Site	Recruiting
Bangkok, Thailand, 10400
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Bangkok, Thailand, 10330
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Chiangmai, Thailand, 50200
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Khon Kaen, Thailand, 40002
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01031069 History of Changes
Other Study ID Numbers:	109823
Study First Received:	December 10, 2009
Last Updated:	February 14, 2013
Health Authority:	Thailand: The Ethical Review Committee for Research in Human Subjects, Ministry of Public health Brazil: ANVISA India: Drugs Controller General of India United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

cervical cancer
HPV vaccine

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Warts
Papillomavirus Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral

Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
DNA Virus Infections
Skin Diseases, Viral
Tumor Virus Infections
Neoplasms
Skin Diseases, Infectious
Skin Diseases

ClinicalTrials.gov processed this record on May 23, 2013