Infections, PapillomavirusPhase 3NCT01627561
Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old
A Phase 3 study testing Cervarix, Priorix and Infanrix in people with Infections, Papillomavirus, run by GlaxoSmithKline at 4 sites in 3 countries.
Trial summary
The current study evaluates the immunogenicity and safety in 4-6 years old female subjects (experimental group) receiving Cervarix according to a 2-dose schedule (Month 0, 6), as compared to 4-6 years old female subjects (control group) receiving sequentially Priorix (Month 0) and Infanrix (Month 6) vaccines. Read more about this study
- Who is it for?
- Ages 4 to 6 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infections, Papillomavirus
- What is being tested?
- Cervarix, Priorix and Infanrix
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 15 Oct 2012to 6 Oct 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 6 years
- Women only
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.)
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Colombia2 sites
GSK Investigational Site
Bogotá, 38007
GSK Investigational Site
Yopal, Casanare
About this study
The current study evaluates the immunogenicity and safety in 4-6 years old female subjects (experimental group) receiving Cervarix according to a 2-dose schedule (Month 0, 6), as compared to 4-6 years old female subjects (control group) receiving sequentially Priorix (Month 0) and Infanrix (Month 6) vaccines.
- Conditions
- Infections, Papillomavirus
- Being tested
- Cervarix, Priorix, Infanrix
- Keywords
- Immune response, Human papillomavirus, HPV vaccine, Safety
- Medical subject headings
- Papillomavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CervarixBiological
Also called HPV
2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6.
PriorixBiological
Also called MMR
1 dose administered intramuscularly in the deltoid muscle of the left arm at Day 0.
InfanrixBiological
Also called DTPa
1 dose administered intramuscularly in the deltoid muscle of the left arm at Month 6.
| Study group | Role | What they receive |
|---|---|---|
| Cervarix Group | Experimental | Healthy female subjects aged between, and including, 4 and 6 years, who received two doses of Cervarix vaccine at Day 0 and Month 6, administered intramuscularly in the deltoid muscle of the left upper arm. Receives: Biological: Cervarix |
| Priorix + Infanrix Group | Active comparator | Healthy female subjects aged between, and including, 4 and 6 years, who received one dose of Priorix vaccine at Day 0 and one dose of Infanrix vaccine at Month 6, administered intramuscularly in the deltoid muscle of the left upper arm. Receives: Biological: Priorix; Biological: Infanrix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Measured: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia (only in joints which were distal from the injection site), drowsiness, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, irritability/fussiness, loss of appetite, myalgia, rash (not urticaria, not measels/rubella-like rash), urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Related = symptom assessed by the investigator as causally related to the study vaccination.
Measured: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) Reported During the 43-day Period Following the Vaccination at Day 0
An unsolicited AE is 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. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 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 = AE assessed by the investigator as causally related to the study vaccination.
Measured: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
Number of Subjects With Any, Grade 3 and Related Unsolicited AEs Reported During the 30-day Period Following the Vaccination at Month 6
An unsolicited AE is 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. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 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 = AE assessed by the investigator as causally related to the study vaccination.
Measured: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Day 42 by Baseline Ranges
The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes [white blood cells] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA).
Abnormal laboratory values at Day 42 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALAT Below (baseline) - Within (Day 42) = ALAT with below normal value at baseline and within normal values at Day 42].
Measured: At Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Month 7 by Baseline Ranges
The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes [white blood cells] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Month 7 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALAT Below (baseline) - Within (Month 7) = ALAT with below normal value at baseline and within normal values at Month 7].
Measured: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Number of Subjects With Serious Adverse Events (SAEs) From Day 0 up to Month 7
SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Measured: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
Number of Subjects With AEs and SAEs Leading to Withdrawal From Day 0 up to Month 7
The number of subjects with AEs and SAEs leading to premature discontinuation of the study was assessed.
Measured: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
Number of Subjects With Potential Immune-mediated Diseases (pIMDs) From Day 0 up to Month 7
pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology.
Measured: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
Number of Subjects With Medically Significant Conditions (MSCs) From Day 0 up to Month 7
MSCs were defined as AEs prompting emergency room or physician visits that were not related to common diseases or were not routine visits for physical examination or vaccination and as SAEs that were not related to common diseases. Common diseases included: upper respiratory tract infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury.
Measured: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7
Seroconversion was defined as a titer greater than or equal to the cut-off value in the serum of seronegative subjects, defined as subjects who had an antibody titer below the cut-off value before vaccination. Titers were measured by Enzyme Linked Immunosorbent Assay (ELISA) and the cut-offs were 19 ELISA Units per milliliter (EU/mL) for HPV-16 and 18 EU/mL for HPV-18.
Measured: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Anti-HPV-16/18 Antibody Concentrations at Month 7
Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EU/mL.
Measured: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Secondary outcomes (18)
Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)
Seroconversion was defined as a titer greater than or equal to the cut-off value in the serum of seronegative subjects, defined as subjects who had an antibody titer below the cut-off value before vaccination. Titers were measured by ELISA and the cut-offs were 19 EU/mL for HPV-16 and 18 EU/mL for HPV-18. Note: Month 7 data are also reported in the Primary outcome measure.
Measured: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)
Antibody concentrations were assessed by ELISA and expressed as GMCs in EU/mL. Note: Month 7 data are also reported in the Primary outcome measure.
Measured: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
Number of Seropositive Subjects for Measles Antigen
A seropositive subject was defined as a subject whose anti-measles antibody titer was equal to or above (≥) 150 milli-International Units per milliliter (mIU/mL), as assessed by ELISA.
Measured: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Anti-measles Antibody Concentrations
Anti-measles antibody concentrations were measured by ELISA, expressed as GMCs, in mIU/mL. The cut-off of the assay was an anti-measles antibody concentration ≥ 150 mIU/mL.
Measured: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Seropositive Subjects for Mumps Antigen
A seropositive subject was defined as a subject whose anti-mumps antibody titer was equal to or above (≥) 231 U/mL, as assessed by ELISA.
Measured: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Anti-mumps Antibody Concentrations
Anti-mumps antibody concentrations were measured by ELISA, expressed as GMCs, in U/mL. The cut-off of the assay was an anti-mumps antibody concentration ≥ 231 U/mL.
Measured: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Seropositive Subjects for Rubella Antigen
A seropositive subject was defined as a subject whose anti-rubella antibody titer was ≥ 4 IU/mL, as assessed by ELISA.
Measured: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Anti-rubella Antibody Concentrations
Anti-rubella antibody concentrations were measured by ELISA, expressed as GMCs, in IU/mL. The cut-off of the assay was an anti-rubella antibody concentration ≥ 4 IU/mL.
Measured: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Seroprotected Subjects Against Diphtheria and Tetanus Antigens
A seroprotected subject against diphtheria antigen was defined as a subject with an anti-diphtheria (anti-D) antibody concentration ≥ the cut-off of 0.1 IU/mL, as measured by ELISA.
A seroprotected subject against tetanus antigen was defined as a subject with an anti-tetanus (anti-T) antibody concentration ≥ the cut-off of 0.1 IU/mL, as measured by ELISA.
Measured: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Number of Subjects With pIMDs From Day 0 up to Month 12
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology.
Measured: From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6)
Number of Subjects With MSCs From Day 0 up to Month 12
MSCs were defined as AEs prompting emergency room or physician visits that were not related to common diseases or were not routine visits for physical examination or vaccination and as SAEs that were not related to common diseases. Common diseases included: upper respiratory tract infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury.
Measured: From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6)
Number of Subjects With SAEs From Day 0 up to Month 12
SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Measured: From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6)
Number of Subjects With SAEs Related to the Investigational Products or Any Fatal SAE
SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Measured: Throughout the study period (i.e. from Day 0 up to Month 12 for Priorix + Infanrix Group and from Day 0 up to Month 36 for Cervarix Group)
Number of Subjects With AEs/SAEs Leading to Withdrawal Throughout the Study Period
The number of subjects with AEs and SAEs leading to premature discontinuation of study was assessed.
Measured: Throughout the study period (i.e from Day 0 up to Month 12 for Priorix + Infanrix Group and from Day 0 up to Month 36 for Cervarix Group)
Number of Subjects Reporting the Intake of Concomitant Medication During the 43-day Period Following the Vaccination at Day 0
Concomitant medication taken at least once during the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0 included: any type of medicines, antipyretics, prophylactic antipyretics and antibiotics.
Measured: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
Number of Subjects Reporting the Intake of Concomitant Medication During the 30-day Period Following the Vaccination at Month 6
Concomitant medication taken at least once during the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6 included: any type of medicines, antipyretics, prophylactic antipyretics and antibiotics.
Measured: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
Percentage of Subjects Completing the Vaccination Schedule in Both Groups
The percentage of subjects who received the specified total number of doses (dose 1, dose 2, any dose) is reported.
Measured: From Day 0 up to Month 6 (i.e. from first vaccination at Day 0 up to the second vaccination at Month 6)
Number of Subjects With Any, Grade 3 and Related to Vaccination Solicited Fever, Measles/Rubella-like Rash, Parotid Gland Swelling and Signs of Meningism Including Febrile Convulsion
Measles/Rubella-like rash: presence of macules, discoloured small patches or spots of the skin, neither elevated nor depressed below the skin's surface and/or papules, raised bumps on the skin usually below (<) 1 cm in diameter.
Parotid/salivary gland swelling: swelling/tenderness in the mandibular/submandibular region.
Suspected signs of meningism including febrile convulsions: febrile convulsions or any other neurological signs or symptoms indicative of meningism.
Any = occurrence of any solicited symptom regardless of their intensity grade or relationship to vaccination. Any fever = axillary temperature equal to or above (≥) 37.5°C. Grade 3 AE = AE which prevented normal, everyday activities. Grade 3 measles/rubella-like rash = more than 150 lesions. Grade 3 parotid gland swelling = swelling with accompanying general symptoms. Grade 3 fever = axillary temperature above (>) 39.0°C. Related = any symptom assessed by the investigator as causally related to the vaccination.
Measured: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2012 (estimated)
- Study start15 Oct 2012
- Primary completion23 Apr 2014
- Study completion6 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infections, PapillomavirusStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01627561
- Sponsor's protocol ID
- 115887
- Other IDs
- 2011-005604-15
- Status last verified
- Mar 2020
- First submitted
- 14 Jun 2012
- Last updated
- 10 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Lin L, Parra MM, Sierra VY, Cespedes AS, Granados MA, Luque A, Damaso S, Castrejon Alba MM, Romano-Mazzotti L, Struyf F. Safety and Immunogenicity of the HPV-16/18 AS04-adjuvanted Vaccine in 4-6-year-old Girls: Results to Month 12 From a Randomized Trial. Pediatr Infect Dis J. 2018 Apr;37(4):e93-e102. doi: 10.1097/INF.0000000000001871.
PubMed 29424799Lin L, Macias Parra M, Sierra VY, Salas Cespedes A, Granados MA, Luque A, Karkada N, Castrejon Alba MM, Romano-Mazzotti L, Borys D, Struyf F. Long-term Immunogenicity and Safety of the AS04-adjuvanted Human Papillomavirus-16/18 Vaccine in Four- to Six-year-old Girls: Three-year Follow-up of a Randomized Phase III Trial. Pediatr Infect Dis J. 2019 Oct;38(10):1061-1067. doi: 10.1097/INF.0000000000002437.
PubMed 31469776Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.
PubMed 41276263
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01627561
- Acronym / sponsor ID
- 115887
- Conditions
- Infections, Papillomavirus
- Keywords
- Immune response, Human papillomavirus, HPV vaccine, Safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2012 (actual)
- Primary completion
- 23 Apr 2014 (actual)
- Study completion
- 6 Oct 2016 (actual)
- First posted
- 26 Jun 2012 (estimated)
- Results
- Posted 8 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study evaluates the immunogenicity and safety in 4-6 years old female subjects (experimental group) receiving Cervarix according to a 2-dose schedule (Month 0, 6), as compared to 4-6 years old female subjects (control group) receiving sequentially Priorix (Month 0) and Infanrix (Month 6) vaccines.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cervarix Group | Experimental | Biological: CervarixHealthy female subjects aged between, and including, 4 and 6 years, who received two doses of Cervarix vaccine at Day 0 and Month 6, administered intramuscularly in the deltoid muscle of the left upper arm. |
| Priorix + Infanrix Group | Active comparator | Biological: Priorix, Biological: InfanrixHealthy female subjects aged between, and including, 4 and 6 years, who received one dose of Priorix vaccine at Day 0 and one dose of Infanrix vaccine at Month 6, administered intramuscularly in the deltoid muscle of the left upper arm. |
Who may qualify
- Ages
- 4 to 6 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (29 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CervarixAlso: HPV2 doses administered intramuscularly in the deltoid muscle of the left arm at Day 0 and Month 6. | Biological | Cervarix Group |
| PriorixAlso: MMR1 dose administered intramuscularly in the deltoid muscle of the left arm at Day 0. | Biological | Priorix + Infanrix Group |
| InfanrixAlso: DTPa1 dose administered intramuscularly in the deltoid muscle of the left arm at Month 6. | Biological | Priorix + Infanrix Group |
Primary outcome
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Assessed solicited general symptoms were arthralgia (only in joints which were distal from the injection site), drowsiness, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, irritability/fussiness, loss of appetite, myalgia, rash (not urticaria, not measels/rubella-like rash), urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Related = symptom assessed by the investigator as causally related to the study vaccination.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) Reported During the 43-day Period Following the Vaccination at Day 0
Time frame: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
An unsolicited AE is 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. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 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 = AE assessed by the investigator as causally related to the study vaccination.
Number of Subjects With Any, Grade 3 and Related Unsolicited AEs Reported During the 30-day Period Following the Vaccination at Month 6
Time frame: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
An unsolicited AE is 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. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 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 = AE assessed by the investigator as causally related to the study vaccination.
Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Day 42 by Baseline Ranges
Time frame: At Day 42 (i.e. 42 days after the vaccination at Day 0)
The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes [white blood cells] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Day 42 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALAT Below (baseline) - Within (Day 42) = ALAT with below normal value at baseline and within normal values at Day 42].
Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Month 7 by Baseline Ranges
Time frame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological (basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes [white blood cells] = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA). Abnormal laboratory values at Month 7 were Below, Within and Above normal ranges, as compared to the baseline status of the same parameter, at Day 0 (Unknown, Below, Within and Above normal ranges) [e.g. ALAT Below (baseline) - Within (Month 7) = ALAT with below normal value at baseline and within normal values at Month 7].
Number of Subjects With Serious Adverse Events (SAEs) From Day 0 up to Month 7
Time frame: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects With AEs and SAEs Leading to Withdrawal From Day 0 up to Month 7
Time frame: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
The number of subjects with AEs and SAEs leading to premature discontinuation of the study was assessed.
Number of Subjects With Potential Immune-mediated Diseases (pIMDs) From Day 0 up to Month 7
Time frame: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology.
Number of Subjects With Medically Significant Conditions (MSCs) From Day 0 up to Month 7
Time frame: From Day 0 up to Month 7 (i.e. from first vaccination at Day 0 up to 30 days after the second vaccination at Month 6)
MSCs were defined as AEs prompting emergency room or physician visits that were not related to common diseases or were not routine visits for physical examination or vaccination and as SAEs that were not related to common diseases. Common diseases included: upper respiratory tract infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury.
Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7
Time frame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Seroconversion was defined as a titer greater than or equal to the cut-off value in the serum of seronegative subjects, defined as subjects who had an antibody titer below the cut-off value before vaccination. Titers were measured by Enzyme Linked Immunosorbent Assay (ELISA) and the cut-offs were 19 ELISA Units per milliliter (EU/mL) for HPV-16 and 18 EU/mL for HPV-18.
Anti-HPV-16/18 Antibody Concentrations at Month 7
Time frame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EU/mL.
18 secondary outcomes
Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)
Time frame: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Month 7, Month 12 (for Both Groups) and at Month 18, Month 24 and Month 36 (Only for Cervarix Group)
Time frame: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
Number of Seropositive Subjects for Measles Antigen
Time frame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Anti-measles Antibody Concentrations
Time frame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Seropositive Subjects for Mumps Antigen
Time frame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Anti-mumps Antibody Concentrations
Time frame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Seropositive Subjects for Rubella Antigen
Time frame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Anti-rubella Antibody Concentrations
Time frame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
Number of Seroprotected Subjects Against Diphtheria and Tetanus Antigens
Time frame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Number of Subjects With pIMDs From Day 0 up to Month 12
Time frame: From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6)
Number of Subjects With MSCs From Day 0 up to Month 12
Time frame: From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6)
Number of Subjects With SAEs From Day 0 up to Month 12
Time frame: From Day 0 up to Month 12 (i.e. from first vaccination at Day 0 up to 6 months after the second vaccination at Month 6)
Number of Subjects With SAEs Related to the Investigational Products or Any Fatal SAE
Time frame: Throughout the study period (i.e. from Day 0 up to Month 12 for Priorix + Infanrix Group and from Day 0 up to Month 36 for Cervarix Group)
Number of Subjects With AEs/SAEs Leading to Withdrawal Throughout the Study Period
Time frame: Throughout the study period (i.e from Day 0 up to Month 12 for Priorix + Infanrix Group and from Day 0 up to Month 36 for Cervarix Group)
Number of Subjects Reporting the Intake of Concomitant Medication During the 43-day Period Following the Vaccination at Day 0
Time frame: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
Number of Subjects Reporting the Intake of Concomitant Medication During the 30-day Period Following the Vaccination at Month 6
Time frame: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
Percentage of Subjects Completing the Vaccination Schedule in Both Groups
Time frame: From Day 0 up to Month 6 (i.e. from first vaccination at Day 0 up to the second vaccination at Month 6)
Number of Subjects With Any, Grade 3 and Related to Vaccination Solicited Fever, Measles/Rubella-like Rash, Parotid Gland Swelling and Signs of Meningism Including Febrile Convulsion
Time frame: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29424799Lin L, Parra MM, Sierra VY, Cespedes AS, Granados MA, Luque A, Damaso S, Castrejon Alba MM, Romano-Mazzotti L, Struyf F. Safety and Immunogenicity of the HPV-16/18 AS04-adjuvanted Vaccine in 4-6-year-old Girls: Results to Month 12 From a Randomized Trial. Pediatr Infect Dis J. 2018 Apr;37(4):e93-e102. doi: 10.1097/INF.0000000000001871.
- Background: PubMed 31469776Lin L, Macias Parra M, Sierra VY, Salas Cespedes A, Granados MA, Luque A, Karkada N, Castrejon Alba MM, Romano-Mazzotti L, Borys D, Struyf F. Long-term Immunogenicity and Safety of the AS04-adjuvanted Human Papillomavirus-16/18 Vaccine in Four- to Six-year-old Girls: Three-year Follow-up of a Randomized Phase III Trial. Pediatr Infect Dis J. 2019 Oct;38(10):1061-1067. doi: 10.1097/INF.0000000000002437.
- Derived from this study: PubMed 41276263Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cervarix, Priorix and Infanrix in people with Infections, Papillomavirus, run by GlaxoSmithKline at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Colombia, Mexico, Panama. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Any and Grade 3 Solicited Local Symptoms (time frame: During the 7-day follow-up period (i.e. from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01627561, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2020.