We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01627561
First Posted: June 26, 2012
Last Update Posted: March 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The current study will evaluate the immunogenicity and safety of Cervarix when administered according to a 2-dose schedule with or without co-administration of GSK Biologicals' MMR and DTPa vaccines in 4-6 years old female subjects as compared to the standard 3-dose schedule in 15-25 years old female subjects, the population in which the clinical efficacy has been demonstrated.

Condition Intervention Phase
Infections, Papillomavirus Biological: Cervarix Biological: Priorix Biological: Infanrix Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms. [ Time Frame: During the 7-day period (Days 0-6) following each vaccination ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Relationship analysis was not performed.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 7-day period (Days 0-6) following each vaccination ]
    Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  • Number of Subjects With Unsolicited Any, Grade 3 and Related Adverse Events (AEs). [ Time Frame: During the 43-day period (Days 0-42) post vaccination Dose 1 ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Unsolicited Any, Grade 3 and Related Adverse Events (AEs). [ Time Frame: During the 30-day period (Days 0-29) post vaccination Dose 2 at Month 6 ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters. [ Time Frame: 42 days post dose 1 (PRE) and at 30 days post dose 2 (POST) ]
    The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin, leukocytes [white blood cells] = WBC, lymphocytes, monocytes, neutrophils and platelets). Results were split into 2 outcomes due to the table size.

  • Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters [ Time Frame: 42 days post dose 1 (PRE) and at 30 days post dose 2 (POST) ]
    The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin, leukocytes [white blood cells] = WBC, lymphocytes, monocytes, neutrophils and platelets). Results were split into 2 outcomes due to the table size.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From first vaccination to one month after the last vaccine dose (from Day 0 up to Month 7) ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Subjects With AEs and SAEs Leading to Withdrawal [ Time Frame: From first vaccination to one month after the last vaccine dose (from Day 0 up to Month 7) ]
  • Number of Subjects With Potential Immune-mediated Diseases (pIMDs) [ Time Frame: From first vaccination to one month after the last vaccine dose (from Day 0 up to Month 7) ]
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology

  • Number of Subjects With Medically Significant Conditions (MSCs) [ Time Frame: From first vaccination to one month after the last vaccine dose (from Day 0 up to Month 7) ]
    MSCs 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 Serconverted Subjects for Anti-HPV-16/18 [ Time Frame: One month after the last dose of study vaccine (Month 7) ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer.

  • Anti-HPV-16/18 Antibody Concentrations [ Time Frame: One month after the last dose of study vaccine (Month 7) ]
    Antibody concentrations were assessed by Enzyme-linked-Immunosorbent Assay (ELISA) and expressed as geometric mean titers (GMTs) in ELISA units per milliliter (EU/mL).


Secondary Outcome Measures:
  • Number of Subjects Seroconverted for Anti-HPV-16/18 Antibodies [ Time Frame: At Day 0, Month 7 and Month 12 ]

    Seroconversion is defined as the appearance of antibodies (i.e. titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.

    Values for Month 7 were primary outcomes and presented as such. Values past month 7 were not available at the time of posting this record and will be added once validated results become available.


  • Anti-HPV-16/18 Antibody Concentrations [ Time Frame: At Day 0, Month 7 and Month 12 ]

    Antibody concentrations were calculated as geometric mean concentrations (GMCs), assessed by ELISA for the respective groups and expressed as ELISA units per milliliter (EU/mL).

    Values for Month 7 were primary outcomes and presented as such. Values past month 7 were not available at the time of posting this record and will be added once validated results become available.


  • Anti-HPV-16/18 Seroconversion Rates Assessed by ELISA in Groups HPV_2D, HPV_2D CO and HPV_3D. [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ]
  • Anti-HPV-16/18 Antibody Titres Assessed by ELISA in Groups HPV_2D, HPV_2D CO and HPV_3D. [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ]
  • Anti-HPV-16/18 Seroconversion Rates Assessed by Pseudovirion-Based Neutralization Assay (PBNA) in a Sub-cohort in Group MMR_DTPa [ Time Frame: At Day 0, Month 7 and Month 12 ]
  • Anti-HPV-16/18 Antibody Titres Assessed by PBNA in a Sub-cohort in Group MMR_DTPa [ Time Frame: At Day 0, Month 7 and Month 12 ]
  • Anti-HPV-16/18 Seroconversion Rates Assessed by PBNA in a Sub-cohort in Groups HPV_2D, HPV_2D CO and HPV_3D. [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ]
  • Anti-HPV-16/18 Antibody Titres Assessed by PBNA in a Sub-cohort in Groups HPV_2D, HPV_2D CO and HPV_3D. [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ]
  • Anti-measles, Mumps and Rubella Seropositivity Rates in Groups HPV_2D, MMR_DTPa and HPV_2D CO. [ Time Frame: On Days 0 and 42 ]
  • Anti-measles, Mumps and Rubella Antibody Titres in Groups HPV_2D, MMR_DTPa and HPV_2D CO. [ Time Frame: On Days 0 and 42 ]
  • Vaccine Response Rates to Filamentous Haemagglutinin (FHA), Pertactin (PRN) and Pertussis Toxoid (PT) Antigens in Groups HPV_2D, MMR_DTPa and HPV_2D CO. [ Time Frame: At Month 7 ]
  • Seroprotection Rates to Diphtheria (D) and Tetanus (T) Antigens in Groups HPV_2D, MMR_DTPa and HPV_2D CO. [ Time Frame: At Month 7 ]
  • The Number of Subjects With Solicited Fever, Measles/Rubella-like Rash, Parotid Gland Swelling and Signs of Meningism, Including Febrile Convulsion [ Time Frame: During the 43-day period (Days 0-42) following vaccination on Day 0 ]
  • Number of Subjects With Potential Immune-mediated Diseases (pIMDs) [ Time Frame: From first vaccination to 6 months after the last vaccine dose (from Day 0 up to Month 12) ]
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology

  • Number of Subjects With Medically Significant Conditions (MSCs) [ Time Frame: From first vaccination to 6 months after the last vaccine dose (from Day 0 up to Month 12) ]
    MSCs 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: From first vaccination to 6 months after the last vaccine dose (from Day 0 up to Month 12) ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the study period (From Day 0 to Month 36) ]
  • Number of Subjects With of AEs/SAEs Leading to Withdrawal [ Time Frame: Throughout the study period (From Day 0 to Month 36) ]
  • Number of Subjects Reporting the Intake of Concomitant Medication [ Time Frame: During the 43-day period (Days 0-42) following vaccination on Day 0 and during the 30-day period (Days 0-29) following vaccination at Month 6 ]
  • The Number of Subjects Completing the Vaccination Schedule in All Groups. [ Time Frame: From first vaccination to the last vaccine dose (from Day 0 up to Month 6) ]
  • Number of Subjects With of AEs/SAEs Leading to Withdrawal [ Time Frame: From Day 0 to Month 12 ]

Enrollment: 149
Study Start Date: October 2012
Study Completion Date: October 2016
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix Group
Subjects aged 4-6 years receiving 2 doses of Cervarix vaccine at Day 0 and Month 6
Biological: Cervarix
2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6 in the HPV_2D and HPV_2D CO Groups 3 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0, Month 1 and Month 6 in the HPV_3D Group
Other Name: HPV
Experimental: Priorix + Infanrix Group
Subjects aged 4-6 years receiving 1 dose of Priorix vaccine at Day 0 and 1 dose of Infanrix vaccine at Month 6
Biological: Priorix
1 dose administered intramuscularly in the deltoid muscle of the left/right arm at Day 0
Other Name: MMR
Biological: Infanrix
1 dose administered intramuscularly in the deltoid muscle of the left/right arm at Month 6
Other Name: DTPa
Experimental: HPV_2D CO group
Subjects aged 4-6 years receiving 2 doses of Cervarix vaccine, the first dose co-administered with Priorix vaccine (at Day 0) and the second one co-administered with Infanrix vaccine (at Month 6)
Biological: Cervarix
2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6 in the HPV_2D and HPV_2D CO Groups 3 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0, Month 1 and Month 6 in the HPV_3D Group
Other Name: HPV
Biological: Priorix
1 dose administered intramuscularly in the deltoid muscle of the left/right arm at Day 0
Other Name: MMR
Biological: Infanrix
1 dose administered intramuscularly in the deltoid muscle of the left/right arm at Month 6
Other Name: DTPa
Active Comparator: HPV_3D group
Subjects aged 15-25 years receiving 3 doses of Cervarix vaccine at Day 0, Month 1 and Month 6
Biological: Cervarix
2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6 in the HPV_2D and HPV_2D CO Groups 3 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0, Month 1 and Month 6 in the HPV_3D Group
Other Name: HPV

Detailed Description:

The study will be conducted in a partially blinded manner:

  • The study will be single-blind for the HPV_2D and MMR_DTPa groups up to the Month 12 visit due to the difference in the visual appearance of the study vaccines. Between Month 12 and study conclusion (Month 36), the study will be open with respect to HPV_2D group.
  • The study will be open with respect to the HPV_2D CO group as subjects in this group will be receiving two vaccines co-administered at each scheduled vaccination visit.
  • The study will be open with respect to the HPV_3D group as subjects in this group will be receiving three injections.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   4 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol.
  • A female between, and including, 4 and 6 years of age at the time of the first vaccination.
  • Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to enrolment in the study.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Subjects who received four doses of DTP vaccine (i.e., three doses in the first year of life and a fourth dose in the second year of life) according to the schedule applicable in the participating countries.
  • Subjects who received a first dose of MMR vaccine according to the schedule applicable in the participating countries.

Exclusion Criteria:

  • Child in care.
  • Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than that foreseen in the protocol.
  • Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of study vaccine(s). Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza and/or poliomyelitis vaccines up to 8 days before the first dose of study vaccine(s) is allowed. Enrolment will be deferred until the subject is outside of specified window.
  • 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(s), or planned use during the study period.
  • History of any reactions or hypersensitivity likely to be exacerbated by any component of the study vaccines, including latex and/or obvious allergic reactions to neomycin (a history of contact dermatitis to neomycin is not a contraindication), egg protein, etc. (e.g. hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock subsequent to egg ingestion).
  • Cancer or autoimmune disease under treatment.
  • 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).
  • Previous administration of MPL or AS04 adjuvant.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine(s) or planned administration during the study period.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • Family history of congenital or hereditary immunodeficiency.
  • Documented human immunodeficiency virus (HIV)-positive subject.
  • Major congenital defects or serious chronic illness.
  • History of seizures or serious neurological disorder, which, according to the judgment of the investigator, precludes administration of any of the study vaccines.
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, which in the opinion of the investigator precludes administration of the study vaccine(s).
  • Acute disease and/or fever at the time of enrolment.
  • Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥ 38.0°C on rectal setting.
  • Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. Enrolment can be deferred until condition is resolved.
  • Previous administration of the fifth dose of DTP vaccine and/or the second dose of MMR vaccine or planned administration of DTP vaccine and/or MMR vaccine outside the study (during the study period from Day 0 to Month 12).
  • History of tetanus, diphtheria, pertussis, measles, mumps and/or rubella.
  • Known exposure to diphtheria or household exposure to pertussis within 30 days prior to vaccination with DTPa.
  • Known exposure to measles, mumps and/or rubella 30 days prior to vaccination with the MMR study vaccine.
  • Confirmed or suspected tuberculosis.
  • Severe allergic reactions (e.g. anaphylaxis or severe Arthus-type hypersensitivity reactions) following the administration of previous dose(s) of DTP or MMR vaccines.
  • Hyperpyrexia (≥ 40.5°C) within 48 hours of administration of previous doses of DTP or MMR vaccines.
  • Persistent, inconsolable crying lasting more than 3 hours, occurring within 48 hours of administration of previous doses of DTP vaccine.
  • Collapse or shocking-like state (hypotonic-hyporesponsive episode) within 48 hours of administration of previous doses of DTP vaccine.
  • Idiopathic thrombocytopenic purpura or bleeding disorders.
  • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose(s). (For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01627561


Locations
Colombia
GSK Investigational Site
Bogota, Colombia, 38007
GSK Investigational Site
Yopal, Casanare, Colombia
Mexico
GSK Investigational Site
Mexico, Mexico, 04530
Panama
GSK Investigational Site
Panama, Panamá, Panama
GSK Investigational Site
Panama, Panama
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01627561     History of Changes
Other Study ID Numbers: 115887
2011-005604-15 ( EudraCT Number )
First Submitted: June 14, 2012
First Posted: June 26, 2012
Results First Submitted: April 23, 2015
Results First Posted: May 8, 2015
Last Update Posted: March 10, 2017
Last Verified: January 2017

Keywords provided by GlaxoSmithKline:
Immune response
Human papillomavirus
HPV vaccine
Safety

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs