Overview

This trial is active, not recruiting.

Condition infections, papillomavirus
Treatments gsk biologicals' hpv vaccine 580299, merck's human papillomavirus quadrivalent (types 6, 11, 16, and 18) vaccine (gardasil)
Phase phase 4
Sponsor GlaxoSmithKline
Start date October 2010
End date January 2016
Trial size 649 participants
Trial identifier NCT01031069, 109823, 2013-003429-28

Summary

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
3 doses of the study vaccine administered according to a Day 0, Week 6, and Month 6 vaccination schedule.
gsk biologicals' hpv vaccine 580299 Cervarix™
Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.
(Active Comparator)
3 doses of the study vaccine administered according to a Day 0, Week 6, and Month 6 vaccination schedule.
merck's human papillomavirus quadrivalent (types 6, 11, 16, and 18) vaccine (gardasil) Gardasil®
Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

Primary Outcomes

Measure
Occurrence and intensity of solicited local symptoms in HIV+ subjects
time frame: During the 7-day (Days 0 - 6) follow-up period after each and any vaccination
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 and any vaccination
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 any vaccination
Occurrence of SAEs up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
Occurrence of medically significant conditions (including potential immune mediated diseases [pIMDs]) up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
Occurrence and outcome of pregnancies up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
Occurrence of clinically relevant abnormalities in hematological and biochemical parameters up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
CD4 cell count up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
HIV viral load up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
HIV clinical staging up to 30 days after the last dose of vaccine in HIV+ subjects
time frame: Throughout the active phase of the study (up to Month 7)
HPV-16 and HPV-18 antibody titers by Pseudovirion-Based Neutralization Assay (PBNA) 30 days after the last dose of vaccine in HIV+ subjects
time frame: At Month 7

Secondary Outcomes

Measure
Occurrence and intensity of solicited local symptoms in HIV- subjects.
time frame: During the 7-day (Days 0 - 6) follow-up period after each and any vaccination
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 and any vaccination
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 any vaccination
Occurrence of SAEs up to 30 days after the last dose of vaccine in HIV- subjects
time frame: Throughout the active phase of the study (up to Month 7)
Occurrence of medically significant conditions (including pIMDs) up to 30 days after the last dose of vaccine in HIV- subjects
time frame: Throughout the active phase of the study (up to Month 7)
Occurrence and outcome of pregnancies in all subjects.
time frame: Throughout the entire study (up to Month 24)
Occurrence of clinically relevant abnormalities in hematological and biochemical parameters in all subjects.
time frame: At Months 12, 18 and 24
Occurrence of SAEs in all subjects.
time frame: Throughout the entire study (up to Month 24)
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)
CD4 cell count, HIV viral load and HIV clinical staging in HIV+ subjects.
time frame: At Months 12, 18 and 24
HPV-16 and HPV-18 antibody titers by Pseudovirion-Based Neutralization Assay (PBNA) in HIV- subjects
time frame: At Month 7
HPV-16 and HPV-18 antibody titers and total Immunoglobulin G (IgG) titers by Enzyme-Linked ImmunoSorbent Assay (ELISA) in serum in all subjects
time frame: At Day 0, Week 6, Week 10, Months 7, 12, 18 and 24
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
Frequencies of HPV-16 and HPV-18 specific B cells and T cells in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-)
time frame: At Day 0, Week 6, Week 10, Months 7 and 12

Eligibility Criteria

Female participants from 15 years up to 25 years old.

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 taking antiretrovirals (ARVs), subjects must be on 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) visit (criteria mandatory only for HIV+ subjects). - 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.

Additional Information

Official title Safety and Immunogenicity of Cervarix™ in Human Immunodeficiency Virus Infected Females
Description This Protocol summary has been updated following Protocol Amendment 7, December 2013, following: • Addition of a new EU country, change in assay and assay cut-off and enrollment of additional subjects and to clarify that some activities in the protocol are mandatory only for HIV+ subjects.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.