Clinical trial NCT01462357: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Human Papillomavirus (HPV) Vaccine (GSK-580299) and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females
Official title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV-16/18 L1 AS04 Vaccine and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: Human papillomavirus
Safety
HPV vaccine
Immune response
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-31
Enrollment: 1079
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the immunogenicity and the safety of Cervarix administered according to a 2-dose schedule at 0, 6 months compared to Gardasil, administered according to a 2-dose schedule at 0, 6 months or the standard 3-dose schedule of 0, 2, 6 months in 9-14 years old healthy females.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes can and will comply with the requirements of the protocol and subjects who the investigator believes their parent(s)/Legally Acceptable Representative(s) (LAR\[s\]) can and will comply with the requirements of the protocol.
* A female between, and including, 9 and 14 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. In addition, if capable, the subject should sign and personally date a written informed assent.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.

Exclusion Criteria:

* Pregnant or breastfeeding.
* A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose.
* Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol.
* Child in care.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 36).
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
* History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines.
* Cancer or autoimmune disease under treatment.
* Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before each dose of vaccine. Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
* 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 vaccine components.
* 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.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* Major congenital defects or serious chronic illness.
* 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.
* Acute disease and/or fever at the time of enrolment.
* Drug and/or alcohol abuse.

Primary outcomes:
measure: Number of Seroconverted Subjects for Anti-HPV-16/18 Antibodies as Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 Based on the ATP Cohort for Immunogenicity
timeFrame: At Month 7 (i.e. one month after the last dose of study vaccine)
measure: Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the ATP Cohort for Immunogenicity
timeFrame: At Month 7 (i.e. one month after the last dose of study vaccine)
measure: Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the Total Vaccinated Cohort (TVC)
timeFrame: At Month 7 (i.e. one month after the last dose of study vaccine)
Secondary outcomes:
measure: Anti-HPV-16/18 Seroconversion Rates as Assessed by ELISA
timeFrame: At Day 0 and Months 12, 18, 24 and 36
measure: Anti-HPV-16/18 Antibody Titers as Assessed by ELISA
timeFrame: At Day 0 and Months 12, 18, 24 and 36
measure: Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 36
timeFrame: At Month 36
measure: Anti-HPV-16/18 Seroconversion Rates as Assessed by Pseudovirion-based Neutralization Assay (PBNA) in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity
timeFrame: At Day 0 and Months 7, 12, 18, 24 and 36
measure: Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity
timeFrame: At Day 0 and Months 7, 12, 18, 24 and 36
measure: Anti-HPV-16/18 Seroconversion Rates as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC
timeFrame: At Day 0 and Months 7, 12, 18, 24 and 36
measure: Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC
timeFrame: At Day 0 and Months 7, 12, 18, 24 and 36
measure: T-cell-mediated Immune Responses in the Sub-cohort for Cell-Mediated Immunity (CMI)
timeFrame: At Day 0 and Months 7, 12, 24 and 36
measure: B-cell-mediated Immune Responses in the Sub-cohort for CMI
timeFrame: At Day 0 and Months 7, 12, 24 and 36
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period
measure: Number of Subjects With Potentially Immune Mediated Diseases (pIMDs)
timeFrame: From Day 0 up to Month 12
measure: Number of Subjects With Medically Significant Conditions (MSCs)
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects With SAEs Related to the Investigational Product, to Study Participation, to GSK Concomitant Products or Any Fatal SAE
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
timeFrame: From Day 0 up to Month 36 (throughout the study period)
measure: Number of Subjects Using a Concomitant Medication Throughout the Study Period
timeFrame: From Day 0 up to Month 36 (throughout the study period) following vaccination after each dose and across doses
measure: Number of Subjects Completing the Vaccination Schedule
timeFrame: From Day 0 up to Month 36 (throughout the study period)
Other outcomes:
Locations:
city: Dax
country: France
facility: GSK Investigational Site
city: Draguignan
country: France
facility: GSK Investigational Site
city: Essey les Nancy
country: France
facility: GSK Investigational Site
city: Le Havre
country: France
facility: GSK Investigational Site
city: Nice
country: France
facility: GSK Investigational Site
city: Paris cedex 20
country: France
facility: GSK Investigational Site
city: Rosiers d'Egletons
country: France
facility: GSK Investigational Site
city: Saint Cyr Sur Loir
country: France
facility: GSK Investigational Site
city: Seysses
country: France
facility: GSK Investigational Site
city: Tours
country: France
facility: GSK Investigational Site
city: Pokfulam
country: Hong Kong
facility: GSK Investigational Site
city: Shatin
country: Hong Kong
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Eskilstuna
country: Sweden
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Leung TF, Liu AP, Lim FS, Thollot F, Oh HM, Lee BW, Rombo L, Tan NC, Rouzier R, Friel D, De Muynck B, De Simoni S, Suryakiran P, Hezareh M, Folschweiller N, Thomas F, Struyf F. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9-14 years: Results to month 12 from a randomized trial. Hum Vaccin Immunother. 2015;11(7):1689-702. doi: 10.1080/21645515.2015.1050570.
citation: Leung TF, Liu AP, Lim FS, Thollot F, Oh HML, Lee BW, Rombo L, Tan NC, Rouzier R, De Simoni S, Suryakiran P, Hezareh M, Thomas F, Folschweiller N, Struyf F. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial. Vaccine. 2018 Jan 2;36(1):98-106. doi: 10.1016/j.vaccine.2017.11.034. Epub 2017 Nov 23.