Clinical trial NCT01627561: Safety and Immunogenicity of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine (GSK-580299) in Healthy Female Children 4-6 Years Old
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: Immune response
Human papillomavirus
HPV vaccine
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-06-26
Enrollment: 148
Sex: FEMALE
Minimum age (years): 4
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility 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.)

Primary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: 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
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: 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
measure: 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
timeFrame: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited AEs Reported During the 30-day Period Following the Vaccination at Month 6
timeFrame: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
measure: Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Day 42 by Baseline Ranges
timeFrame: At Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters at Month 7 by Baseline Ranges
timeFrame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
measure: Number of Subjects With Serious Adverse Events (SAEs) From Day 0 up to Month 7
timeFrame: 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)
measure: Number of Subjects With AEs and SAEs Leading to Withdrawal From Day 0 up to Month 7
timeFrame: 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)
measure: Number of Subjects With Potential Immune-mediated Diseases (pIMDs) From Day 0 up to Month 7
timeFrame: 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)
measure: Number of Subjects With Medically Significant Conditions (MSCs) From Day 0 up to Month 7
timeFrame: 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)
measure: Number of Seroconverted Subjects for HPV-16 and HPV-18 Antigens at Month 7
timeFrame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
measure: Anti-HPV-16/18 Antibody Concentrations at Month 7
timeFrame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
Secondary outcomes:
measure: 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)
timeFrame: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
measure: 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)
timeFrame: At Month 7, Month 12 (for both groups) and at Month 18, Month 24 and Month 36 (only for Cervarix Group)
measure: Number of Seropositive Subjects for Measles Antigen
timeFrame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Anti-measles Antibody Concentrations
timeFrame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Number of Seropositive Subjects for Mumps Antigen
timeFrame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Anti-mumps Antibody Concentrations
timeFrame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Number of Seropositive Subjects for Rubella Antigen
timeFrame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Anti-rubella Antibody Concentrations
timeFrame: At Day 0 and Day 42 (i.e. 42 days after the vaccination at Day 0)
measure: Number of Seroprotected Subjects Against Diphtheria and Tetanus Antigens
timeFrame: At Month 7 (i.e. 30 days after the vaccination at Month 6)
measure: Number of Subjects With pIMDs From Day 0 up to Month 12
timeFrame: 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)
measure: Number of Subjects With MSCs From Day 0 up to Month 12
timeFrame: 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)
measure: Number of Subjects With SAEs From Day 0 up to Month 12
timeFrame: 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)
measure: Number of Subjects With SAEs Related to the Investigational Products or Any Fatal SAE
timeFrame: 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)
measure: Number of Subjects With AEs/SAEs Leading to Withdrawal Throughout the Study Period
timeFrame: 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)
measure: Number of Subjects Reporting the Intake of Concomitant Medication During the 43-day Period Following the Vaccination at Day 0
timeFrame: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
measure: Number of Subjects Reporting the Intake of Concomitant Medication During the 30-day Period Following the Vaccination at Month 6
timeFrame: During the 30-day period (i.e. from the day of vaccination up to 29 subsequent days) following the vaccination at Month 6
measure: Percentage of Subjects Completing the Vaccination Schedule in Both Groups
timeFrame: From Day 0 up to Month 6 (i.e. from first vaccination at Day 0 up to the second vaccination at Month 6)
measure: 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
timeFrame: During the 43-day period (i.e. from the day of vaccination up to 42 subsequent days) following the vaccination at Day 0
Other outcomes:
Locations:
city: Bogota
country: Colombia
facility: GSK Investigational Site
city: Yopal, Casanare
country: Colombia
facility: GSK Investigational Site
city: Mexico
country: Mexico
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Lin 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.