Clinical trial NCT00586339: Safety and Immunogenicity of GlaxoSmithKline Biologicals' HPV Vaccine 580299 (Cervarix) in HIV Infected Females
Official title: Evaluation of the Safety and Immunogenicity of GlaxoSmithKline Biologicals' HPV Vaccine 580299 (Cervarix) in Adult Human Immunodeficiency Virus (HIV) Infected Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Papillomavirus
Keywords: HPV
Human papillomavirus (HPV) vaccine
Human Immunodeficiency Virus (HIV)
Cervical cancer
Papillomavirus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-01-04
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. The current study is designed to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' HPV vaccine 580299 in HIV infected adult females living in the Republic of South Africa. The study is double blinded, randomized for HIV positive subjects and open for HIV negative subjects. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that they can and will comply with the requirements of the protocol
* A female between, and including, 18 and 25 years of age at the time of the first vaccination.
* Written, signed or thumb-printed informed consent obtained from the subject prior to enrolment.
* Subjects willing to undergo HIV Voluntary Counseling and Testing (VCT) and willing to be informed of their HIV status.
* Subjects willing to provide place of residence and be visited at home.
* HIV seropositive subjects:

  1. Subjects must be HIV seropositive according to WHO case definition
  2. Subjects with WHO Clinical Stage 1 HIV-associated disease
  3. Subjects currently on antiretroviral therapy (ART) must be compliant to ART and have undetectable viral load
* HIV seronegative subjects: Subjects confirmed as HIV seronegative at the screening visit are eligible to participate in the HIV-/HPV group of the study.
* Non-virgin subjects must have a normal colposcopy at the screening visit.
* Non-virgin subjects must have a normal cervical cytology (Pap smear) or no greater than atypical squamous cells of undetermined significance (ASC-US) at the screening visit.
* All subjects must have a negative urine pregnancy test at the screening visit and at visit 1 (Day 0).
* Subjects must be of non-childbearing potential or, if of childbearing potential, must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
* Subjects must have had no more than 6 life-time sexual partners prior to enrolment.
* Subjects must have one single intact cervix

Exclusion Criteria:

* Active tuberculosis (TB)
* Current TB prophylaxis or therapy.
* Anemia at the screening visit.
* increased creatinine at the screening visit.
* Increased hepatic enzym (ALT) at the screening visit
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine/control, or planned use during the entire study period (up to Month 12).
* Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
* Administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of study vaccine/control. Enrolment 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 vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (Month 0 to Month 12).
* 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 at the time of enrolment.
* 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.
* Concurrently participating in another clinical study, at any time during the study period (up to Month 12), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* 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. Enrolment will be postponed until the subject is outside the specified window.
* Administration of trimethoprim/sulphamethoxazole within 7 days before the first dose of study vaccine/control, or planned administration of trimethoprim/sulphamethoxazole within 7 days after the first dose of study vaccine/control.
* Current drugs or alcohol abuse.

Primary outcomes:
measure: Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms
timeFrame: Within 7 days after each dose and across doses
measure: Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms
timeFrame: Within 7 days after each dose and across doses
measure: Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms
timeFrame: Within 30 days after any vaccination
measure: Number of Subjects With Medically Significant Conditions (MSCs) From Day 0 up to Month 7
timeFrame: From Day 0 up to Month 7
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) From Day 0 up to Month 7
timeFrame: From Day 0 up to Month 7
measure: Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies From Day 0 up to Month 7
timeFrame: From Day 0 up to Month 7
measure: Number of Subjects Reporting SAEs From Day 0 up to Month 12
timeFrame: From Day 0 up to Month 12
measure: Number of Subjects With MSCs From Day 0 up to Month 12
timeFrame: From Day 0 up to Month 12
measure: Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies From Day 0 up to Month 12
timeFrame: From Day 0 up to Month 12
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Red Blood Cells and Platelets Parameters at Day 7 and at Months 1, 2, 4, 6 and 7
timeFrame: At Day 7 and at Months 1, 2, 4, 6 and 7
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in White Blood Cells and Neutrophils Parameters at Day 7 and Months 1, 2, 4, 6 and 7
timeFrame: At Day 7 and Months 1, 2, 4, 6 and 7
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Lymphocytes and Monocytes Parameters at Day 7 and Months 1, 2, 4, 6 and 7
timeFrame: At Day 7 and at Months 1, 2, 4, 6 and 7
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Haemoglobin and Haematocrit Parameters at Day 7 and Months 1, 2, 4, 6 and 7
timeFrame: At Day 7 and Months 1, 2, 4, 6 and 7
measure: Number of Subjects With Clinically Relevant Abnormalities in Eosinophils, Basophils and Creatinine Parameters at Day 7 and Months 1, 2, 4, 6 and 7
timeFrame: At Day 7 and at Months 1, 2, 4, 6 and 7
measure: Number of Subjects With Clinically Relevant Abnormalities in Alanine Aminotransferase Parameter at Day 7 and Months 1, 2, 4, 6 and 7
timeFrame: At Day 7 and Months 1, 2, 4, 6 and 7
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Neutrophils, Platelets, Red Blood Cells and White Blood Cells at Month 10 and Month 12
timeFrame: At Month 10 and Month 12
measure: Number of Subjects With Clinically Relevant Abnormalities in Alanine Aminotransferase, Basophils, Creatinine, Eosinophils, Haematocrit, Haemoglobin, Lymphocytes and Monocytes Parameters at Month 10 and Month 12
timeFrame: At Month 10 and Month 12
measure: Number of Cluster of Differention 4 (CD4+) Cells Per Cubic Millimeter in All HIV+ Subjects at Pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7
timeFrame: At pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7
measure: Number of CD4+ Cells Per Cubic Millimeter in All HIV+ Subjects at Month 10 and Month 12
timeFrame: At Month 10 and Month 12
measure: HIV Viral Load in All HIV+ Subjects at Pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7
timeFrame: At pre-vaccination (Day 0) and Months 1, 2, 4, 6 and 7
measure: HIV Viral Load in All HIV+ Subjects at Month 10 and Month 12
timeFrame: At Month 10 and Month 12
measure: Number of Subjects in Each World Health Organisation (WHO) HIV Clinical Stage by CD4+ Cell Count Category at Baseline in All HIV+ Subjects at Months 1, 2, 4, 6 and 7
timeFrame: At Months 1, 2, 4, 6 and 7
measure: Number of Subjects in Each World Health Organisation (WHO) HIV Clinical Stage by CD4+ Cell Count Category at Baseline in All HIV+ Subjects at Month 10 and Month 12
timeFrame: At Month 10 and Month 12
measure: Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies at Pre-vaccination (Day 0) and Months 2 and 7
timeFrame: At pre-vaccination (Day 0) and Months 2 and 7
measure: Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies at Month 12
timeFrame: At Month 12
measure: Concentrations for HPV-16 and HPV-18 Antibodies at Pre-vaccination (Day 0) and Months 2 and 7
timeFrame: At pre-vaccination (Day 0) and Months 2 and 7
measure: Concentrations for HPV-16 and HPV-18 Antibodies at Month 12
timeFrame: At Month 12
measure: Cell Mediated Immune (CMI) Response (B-cell Responses) Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Day 0
timeFrame: At pre-vaccination (Day 0)
measure: CMI B-cell Responses Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Month 2
timeFrame: At Month 2
measure: CMI B-cell Responses Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Month 7
timeFrame: At Month 7
measure: CMI B-cell Responses Related to HPV 16/18 Virus-like Particles (VLPs) Measured by Flow Cytometry at Month 12
timeFrame: At Month 12
measure: CMI Response (T-cell Responses) Related to HPV-16 and HPV-18 Measured by Intracellular Cytokine Staining (ICS)
timeFrame: At pre-vaccination (Day 0) and at Months 2, 7 and 12
Secondary outcomes:
Other outcomes:
Locations:
city: Khayelitsha
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Denny L, Hendricks B, Gordon C, Thomas F, Hezareh M, Dobbelaere K, Durand C, Herve C, Descamps D. Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study. Vaccine. 2013 Nov 19;31(48):5745-53. doi: 10.1016/j.vaccine.2013.09.032. Epub 2013 Oct 1.