Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV Vaccine 580299 in Healthy Females 10 - 25 Years of Age.

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00481767
First received: May 31, 2007
Last updated: April 7, 2011
Last verified: March 2011
  Purpose

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. The current study is designed to assess the immunogenicity and safety of GlaxoSmithKline Biologicals' HPV vaccine 580299 in female subjects aged 10-25 years enrolled in Africa.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
HPV-16/18 Infections
Cervical Neoplasia
Biological: CervarixTM
Biological: Placebo vaccine (Al(OH)3)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Study to Assess the Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV Vaccine GSK580299 in Healthy Female Subjects Aged 10-25 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seroconverted Subjects for Anti-human Papillomavirus (HPV)-16 and 18 Antibodies [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]

    A seroconverted subject was a subject with antibody titers below 8 or 7 Enzyme-linked Immunosorbent Assay Units per milliliter (EL.U/mL) for anti-HPV-16 and 18, respectively, before vaccination and antibody titers >= 8 or 7 EL.U/mL for anti-HPV-16 and 18, respectively, after vaccination.

    The groups were stratified by age for the analysis. The age strata were 10-14 years and 15-25 years.


  • Geometric Mean Titers (GMTs) of Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]

    Titers were expressed as GMTs in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

    The groups were stratified by age for the analysis. The age strata were 10-14 years and 15-25 years.



Secondary Outcome Measures:
  • Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: At Month 2 and Month 12 ] [ Designated as safety issue: No ]

    A seroconverted subject was a subject with antibody titers below 8 or 7 Enzyme-linked Immunosorbent Assay Units per milliliter (EL.U/mL) for anti-HPV-16 and 18, respectively, before vaccination and antibody titers >= 8 or 7 EL.U/mL for anti-HPV-16 and 18, respectively, after vaccination.

    The groups were stratified by age for the analysis. The age strata were 10-14 years and 15-25 years.


  • GMTs for Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: At Month 2 and Month 12 ] [ Designated as safety issue: No ]

    Titers were expressed as GMTs in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

    The groups were stratified by age for the analysis. The age strata were 10-14 years and 15-25 years.


  • Number of Subjects With Solicited Local and General Symptoms [ Time Frame: Within 7 days (Day 0-6) after vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms were pain and swelling at the injection site. Solicited general symptoms were arthralgia, fatigue, fever (defined as axillary temperature >= 37.5 degrees Celsius), gastrointestinal symptoms, headache, myalgia, rash and urticaria.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: Within 30 days (Day 0-29) after any vaccination ] [ Designated as safety issue: No ]

    Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

    Any= any unsolicited AE regardless of intensity and relationship to vaccination.

    Grade 3= an unsolicited AE that prevented normal everyday activity Related= unsolicited AE assessed by the investigator as causally related to the study vaccination.


  • Number of Subjects With New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSCs) [ Time Frame: Up to Month 7 and from Month 7 up to Month 12 ] [ Designated as safety issue: No ]
    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Up to Month 7 and up to Month 12 ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Number of Subjects With Pregnancies and Their Outcomes [ Time Frame: Up to Month 12 ] [ Designated as safety issue: No ]
    Pregnancy outcomes were ectopic pregnancy, elective termination no apparent congenital anomaly, live infant no apparent congenital anomaly, premature live infant no apparent congenital anomaly, lost to follow-up and spontaneous abortion no apparent congenital anomaly.

  • Number of Senegalese Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters Assessed [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]

    Parameters assessed were:

    Alanine amino-transferase (ALT), basophils (BAS), creatinine (CREA), eosinophils (EOS), hematocrit (HC), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC).

    Number of subjects were separated with respect to their results at pre-vaccination, i.e. whether their results were in, above or below the normal range. N for each category at pre-vaccination noted in category title.

    For each parameter and for each range it was assessed whether the values of the subjects were in, above or below the normal range.


  • Number of Tanzanian Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters Assessed [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Parameters assessed were: Alanine amino-transferase (ALT), basophils (BAS), creatinine (CREA), eosinophils (EOS), hematocrit (HC), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC). Number of subjects were separated with respect to their results at pre-vaccination, i.e. whether their results were in, above or below the normal range. N for each category at pre-vaccination noted in category title. For each parameter and for each range it was assessed whether the values of the subjects were in, above or below the normal range.

  • Number of Senegalese Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters Assessed [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
    Parameters assessed were: Alanine amino-transferase (ALT), basophils (BAS), creatinine (CREA), eosinophils (EOS), hematocrit (HC), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC). Number of subjects were separated with respect to their results at pre-vaccination, i.e. whether their results were in, above or below the normal range. N for each category at pre-vaccination noted in category title. For each parameter and for each range it was assessed whether the values of the subjects were in, above or below the normal range.

  • Number of Tanzanian Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters Assessed [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
    Parameters assessed were: Alanine amino-transferase (ALT), basophils (BAS), creatinine (CREA), eosinophils (EOS), hematocrit (HC), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC). Number of subjects were separated with respect to their results at pre-vaccination, i.e. whether their results were in, above or below the normal range. N for each category at pre-vaccination noted in category title. For each parameter and for each range it was assessed whether the values of the subjects were in, above or below the normal range.


Enrollment: 676
Study Start Date: October 2007
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix Group
Female subjects received 3 doses of Cervarix at Month 0, 1 and 6 intramuscularly into the deltoid region of the non-dominant arm. For some analyses the group was stratified by age into a 10-14 years of age group and a 15-25 years of age group.
Biological: CervarixTM
Three doses of vaccine/control will be administered according to a 0, 1, 6 month schedule
Other Names:
  • GlaxoSmithKline Biologicals' HPV vaccine 58029
  • HPV-16/18 L1 AS04 vaccine
Active Comparator: Placebo Group
Female subjects received 3 doses of placebo at Month 0, 1 and 6 intramuscularly into the deltoid region of the non-dominant arm. For some analyses the group was stratified by age into a 10-14 years of age group and a 15-25 years of age group.
Biological: Placebo vaccine (Al(OH)3)
Three doses of vaccine/control will be administered according to a 0, 1, 6 month schedule

  Eligibility

Ages Eligible for Study:   10 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 parents/legally acceptable representative can and will comply with the requirements of the protocol should be enrolled in the study.
  • A female between, and including, 10 and 25 years of age at the time of the first vaccination.
  • Written or oral, signed or thumb printed or witnessed informed consent obtained from the subject prior to enrolment. For subjects below legal age of consent, written or oral, signed or thumb printed or witnessed informed consent obtained from the subject's parent or legally acceptable representative. In addition, a written or oral, signed or thumb printed and witnessed informed assent must be obtained from the subject.
  • Free of obvious health problems as established by medical history, clinical examination and laboratory testing before entering into the study.
  • Subjects must have a negative urine pregnancy test at the screening visit and at Visit 1 (Day 0).
  • Subjects must be seronegative for human immunodeficiency virus (HIV) at the screening visit.
  • Subjects must be of non-childbearing potential, or, if of childbearing potential, she 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 who reach menarche during the study and therefore are of childbearing potential must agree to follow the same precautions.
  • Subjects must have had no more than 6 sexual partners prior to enrolment.
  • Subjects must be willing to undergo HIV voluntary counselling and testing and must be willing to be informed of their HIV status. Subjects below legal age of consent must also be willing to have their parent or legally acceptable representative informed of their HIV status.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 12).
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study period.
  • Administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. Enrolment will be deferred until the subject is outside of specified window.
  • Planned administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after 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.
  • Previous administration of components of the investigational vaccine
  • Cancer or autoimmune disease under treatment.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection based on laboratory testing performed during the screening visit.
  • 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 neurologic disorders or seizures.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
  • Pregnant or breastfeeding female.
  • A women planning to become pregnant, likely to become pregnant 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, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481767

Locations
Senegal
GSK Investigational Site
Dakar, Senegal
Tanzania
GSK Investigational Site
Mwanza, Tanzania
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00481767     History of Changes
Other Study ID Numbers: 106069
Study First Received: May 31, 2007
Results First Received: February 24, 2011
Last Updated: April 7, 2011
Health Authority: Senegal: Ministere de la sante
Tanzania: TFDA (Tanzania Food and Drugs Authority)

Keywords provided by GlaxoSmithKline:
Cervical cancer;
Human papillomavirus (HPV) vaccine
HPV;
Papillomavirus;

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 31, 2014