Clinical trial NCT01755689: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Vaccine With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults
Official title: Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Vaccine 134612 With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults at 9-25 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Meningococcal
Keywords: pertussis
Meningococcal meningitis
Meningococcal infections
HPV
Neisseria meningitidis
Vaccines, conjugate
tetanus
diphtheria
Meningococcal vaccines
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-12-24
Enrollment: 1300
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate safety and immunogenicity of GSK Biologicals' meningococcal vaccine GSK134612 (MenACWY-TT) co-administered with Cervarix as compared to MenACWY-TT and Cervarix administered alone and the co-administration of MenACWY-TT with Cervarix and Boostrix as compared to MenACWY-TT administered alone and Cervarix co-administered with Boostrix.


Eligibility criteria: Inclusion Criteria:

* Subjects and subjects' parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
* A female between, and including, 9 and 25 years of age at the time of the first vaccination.
* Written informed consent obtained from parents/guardian of the subject and written informed assent obtained from the subject if the subject is less than legal age, or written informed consent obtained from the subject if the subject has achieved legal age. The legal age will be determined according to local regulations in each participating country.
* 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.

  * Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
* 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 2 months after completion of the vaccination series.

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will be ≥10 mg/day prednisone or equivalent. Inhaled and topical steroids are allowed.
* Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after each study dose of vaccine(s), with the exception of licensed inactivated influenza vaccine.
* 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 product or a non-investigational vaccine/product.
* Previous vaccination with a meningococcal polysaccharide or conjugate vaccine within the last 10 years.
* History of meningococcal disease since birth.
* History of serious allergic reaction following any other DTP-containing vaccine or any component of the study vaccines.
* History of encephalopathy within seven days of administration of a previous pertussis antigen-containing vaccine that is not attributable to another identifiable cause.
* Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of tetanus-toxoid containing vaccine should not receive Boostrix unless at least 10 years have elapsed since the last dose of tetanus-toxoid containing vaccine.
* Previous vaccination with a tetanus-toxoid containing vaccine within the previous five years.
* Temperature of ≥ 40.5°C (105°F) within 48 hours of receipt of a previous dose of DTP vaccine (diphtheria-tetanus-whole cell pertussis \[DTPw\] and/or diphtheria-tetanus-acellular pertussis \[DTaP\]), not due to another identifiable cause.
* Collapse or shock-like state within 48 hours of receipt of a previous dose of DTP vaccine.
* Seizures with or without fever within three days of a previous dose of DTP vaccine.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and history directed physical examination.
* A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
* History of any allergic disease/reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
* Progressive neurologic disorder, unstable neurologic conditions, uncontrolled epilepsy or progressive encephalopathy.
* History of any neurologic disorders or seizures. A history of ADHD or depression or a history of a single, simple febrile seizure does not exclude a subject.
* Major congenital defects or serious chronic illness.
* Previous history of Guillain-Barré Syndrome.
* Bleeding disorders, such as hemophilia or thrombocytopenia, or subjects on anti-coagulant therapy.
* Acute disease and/or fever at the time of enrolment.
* 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.
* Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
* Previous administration of MPL or AS04 adjuvant.
* History of chronic alcohol consumption and/or drug abuse.
* Pregnant or lactating female.
* A subject planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
* Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.

Primary outcomes:
measure: Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA)
timeFrame: At one month after vaccination with Nimenrix (Month 1)
measure: Anti-HPV-16 and Anti-HPV-18 Concentrations
timeFrame: At one month after vaccination with Cervarix (Month 7)
measure: Number of Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Concentrations Equal to or Above (≥) 1.0 IU/mL
timeFrame: At one month after Boostrix vaccination (Month 1)
measure: Anti-Pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
timeFrame: At one month after Boostrix vaccination (Month 1)
Secondary outcomes:
measure: Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titres ≥ 1:8 and ≥ 1:128
timeFrame: Prior to and one month after vaccination with Nimenrix (Months 0 and 1)
measure: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Vaccine Response
timeFrame: At one month after Nimenrix vaccination (Month 1)
measure: Number of Subjects With Anti-T Antibody Concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL
timeFrame: Prior to and one month after vaccination with Nimenrix (Months 0 and 1)
measure: Anti-T Antibody Concentrations
timeFrame: Prior to and one month after vaccination with Nimenrix (Months 0 and 1)
measure: Number of Subjects With Anti-HPV-16 Concentrations ≥ 19 EU/mL and Anti-HPV-18 Concentrations ≥ 18 EU/mL
timeFrame: Prior to the first dose and one month after the third dose of Cervarix [Month 0 and Month 7/Month 8 in Nimenrix+Cervarix (1,2,7-Month) Group]
measure: Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies
timeFrame: Prior to and one month after the third dose of Cervarix (Month 0 and Month 7/Month 8)
measure: Anti-HPV-16 and Anti-HPV-18 Concentrations
timeFrame: Prior to and one month after the third dose of Cervarix (Months 0 and 8)
measure: Booster Responses for Anti-PT, Anti-FHA and Anti-PRN Antibodies
timeFrame: At one month after Boostrix vaccination (Month 1)
measure: Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL
timeFrame: Prior to and one month after Boostrix vaccination (Month 0 and Month 1)
measure: Anti-D and Anti-T Antibody Concentrations
timeFrame: Prior to and one month after Boostrix vaccination (Months 0 and 1)
measure: Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Equal to or Above the Cut-off Value
timeFrame: Prior to and one month after Boostrix vaccination (Months 0 and 1)
measure: Number of Subjects Reporting Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects Reporting Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Unsolicited Adverse Events AE(s)
timeFrame: During the 31-day (Days 0-30) period following vaccination with Nimenrix, Boostrix or the first dose of Cervarix
measure: Number of Subjects With Serious Adverse Events SAE(s)
timeFrame: During the entire study period (from Month 0 to Month 8)
measure: Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
timeFrame: During the entire study period (from Month 0 to Month 8)
measure: Number of Subjects With New Onset Chronic Illnesses (NOCIs)
timeFrame: During the entire study period (from Month 0 to Month 8)
Other outcomes:
Locations:
city: Santo Domingo
country: Dominican Republic
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rivera L, Chanthavanich P, Poder A, Suryakiran PV, Jastorff A, Van der Wielen M. MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial. Vaccine. 2018 Jun 22;36(27):3967-3975. doi: 10.1016/j.vaccine.2018.05.051. Epub 2018 May 19.