Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT01755689
Recruitment Status : Completed
First Posted : December 24, 2012
Results First Posted : July 3, 2018
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE December 13, 2012
First Posted Date  ICMJE December 24, 2012
Results First Submitted Date  ICMJE June 16, 2017
Results First Posted Date  ICMJE July 3, 2018
Last Update Posted Date July 3, 2018
Actual Study Start Date  ICMJE January 11, 2013
Actual Primary Completion Date April 29, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA) [ Time Frame: At one month after vaccination with Nimenrix (Month 1) ]
    The analysis was performed for the serogroups -MenA, -MenC -MenW-135 and -MenY. Antibody titers, tabulated as geometric mean titers (GMTs), were obtained by serum bactericidal assay using rabbit complement. This analysis was only performed on groups receiving Nimenrix vaccine.
  • Anti-HPV-16 and Anti-HPV-18 Concentrations [ Time Frame: At one month after vaccination with Cervarix (Month 7) ]
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL).
  • Number of Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Concentrations Equal to or Above (≥) 1.0 IU/mL [ Time Frame: At one month after Boostrix vaccination (Month 1) ]
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL). This analysis was only performed on the groups receiving Boostrix vaccine.
  • Anti-Pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At one month after Boostrix vaccination (Month 1) ]
    The antibody concentrations were tabulated as GMCs and expressed as IU/mL. GMCs were only analyzed in subjects receiving Boostrix vaccination.
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2012)
  • Immunogenicity with respect to components of the investigational vaccine in terms of antibody titres. [ Time Frame: One month after vaccination with MenACWY-TT (Month 1). ]
  • Immunogenicity with respect to the components of Cervarix in terms of antibody titres. [ Time Frame: One month after the 3rd dose of Cervarix (Month 7). ]
  • Immunogenicity with respect to the components of Boostrix in terms of antibody concentrations. [ Time Frame: One month after vaccination with Boostrix (Month 1). ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titres ≥ 1:8 and ≥ 1:128 [ Time Frame: Prior to and one month after vaccination with Nimenrix (Months 0 and 1) ]
    The number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titers ≥ 1:8 and ≥ 1:128 prior to and one month after vaccination with Nimenrix vaccine.
  • rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Vaccine Response [ Time Frame: At one month after Nimenrix vaccination (Month 1) ]
    rSBA vaccine response for serogroups A, C, W-135 and Y was defined as:
    • For initially seronegative subjects (pre-vaccination titre below the cut-off of 1:8): number of subjects with rSBA antibody titres ≥ 1:32 one month after vaccination.
    • For initially seropositive subjects (pre-vaccination titre ≥ 1:8): number of subjects with rSBA antibody titres at least four times the pre-vaccination antibody titres, one month after vaccination.
  • Number of Subjects With Anti-T Antibody Concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL [ Time Frame: Prior to and one month after vaccination with Nimenrix (Months 0 and 1) ]
    The antibody concentrations were tabulated as GMCs and expressed as IU/mL, only for the Nimenrix+Cervarix (1,2,7-Month) Group.
  • Anti-T Antibody Concentrations [ Time Frame: Prior to and one month after vaccination with Nimenrix (Months 0 and 1) ]
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). This analysis was only performed for the Nimenrix+Cervarix (1,2,7-Month) Group.
  • Number of Subjects With Anti-HPV-16 Concentrations ≥ 19 EU/mL and Anti-HPV-18 Concentrations ≥ 18 EU/mL [ Time Frame: 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] ]
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL).
  • Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: Prior to and one month after the third dose of Cervarix (Month 0 and Month 7/Month 8) ]
    Seroconversion rate is defined as the appearance of antibodies (i.e. titers greater than or equal to the cut-off value) in the serum of subjects who are seronegative before vaccination. The antibody concentrations were calculated as GMCs and expressed as EU/mL.
  • Anti-HPV-16 and Anti-HPV-18 Concentrations [ Time Frame: Prior to and one month after the third dose of Cervarix (Months 0 and 8) ]
    The antibody concentrations were calculated as GMCs and expressed as EU/mL, only for the Nimenrix+Cervarix (1,2,7-Month) Group.
  • Booster Responses for Anti-PT, Anti-FHA and Anti-PRN Antibodies [ Time Frame: At one month after Boostrix vaccination (Month 1) ]
    Booster responses to the PT, FHA and PRN antigens were defined as:
    • For initially seronegative subjects (antibody concentrations: < 2.046 IU/ml for anti-FHA, < 2.187 IU/ml for anti-PRN, < 2.693 IU/ml for anti-PT), antibody concentration ≥ 4*cut_off IU/ml at Month 1 post-vaccination;
    • For initially seropositive subjects (antibody concentrations: ≥ 2.046 IU/ml for anti-FHA, ≥ 2.187 IU/ml for anti-PRN, ≥ 2.693 IU/ml for anti-PT) with pre-vaccination antibody concentration < 4*cut_off IU/ml : antibody concentration at Month 1 ≥ 4 fold the pre-vaccination antibody concentration;
    • For initially seropositive subjects (antibody concentrations: ≥ 2.046 IU/ml for anti-FHA, ≥ 2.187 IU/ml for anti-PRN, ≥ 2.693 IU/ml for anti-PT) with pre-vaccination antibody concentration ≥ 4*cut_off IU/ml : antibody concentration at Month 1 ≥ 2 fold the pre-vaccination antibody concentration.
  • Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL [ Time Frame: Prior to and one month after Boostrix vaccination (Month 0 and Month 1) ]
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL).
  • Anti-D and Anti-T Antibody Concentrations [ Time Frame: Prior to and one month after Boostrix vaccination (Months 0 and 1) ]
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL).
  • Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Equal to or Above the Cut-off Value [ Time Frame: Prior to and one month after Boostrix vaccination (Months 0 and 1) ]
    The antibody concentrations were calculated as GMCs and expressed as IU/mL. Anti-PT assay cut-off=2.693 IU/mL, anti-FHA assay cut-off=2.046 IU/mL, anti-PRN assay cut-off=2.187 IU/mL.
  • Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each 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 = significant pain at rest, prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Symptoms were presented by vaccination site. Some groups do not have results for "Dose 2" because solicited local symptoms were not collected for these subjects at the Dose 2 timepoint.
  • Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]
    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. Some groups do not have results for "Dose 2" because solicited local symptoms were not collected for these subjects at the Dose 2 timepoint.
  • Number of Subjects With Unsolicited Adverse Events AE(s) [ Time Frame: During the 31-day (Days 0-30) period following vaccination with Nimenrix, Boostrix or the first dose of Cervarix ]
    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 Serious Adverse Events SAE(s) [ Time Frame: During the entire study period (from Month 0 to Month 8) ]
    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 Potential Immune-mediated Diseases (pIMDs) [ Time Frame: During the entire study period (from Month 0 to Month 8) ]
    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 New Onset Chronic Illnesses (NOCIs) [ Time Frame: During the entire study period (from Month 0 to Month 8) ]
    NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2012)
  • Immunogenicity with respect to the components of the investigational vaccine in terms of antibody titres and vaccine response. [ Time Frame: Prior to (Day 0) and one month after vaccination with MenACWY-TT (Month 1). ]
  • Immunogenicity with respect to the components of the investigational vaccine in terms of antibody concentrations. [ Time Frame: Prior to (Day 0) and one month after vaccination with MenACWY-TT (Month 1). ]
  • Immunogenicity with respect to the components of Cervarix in terms of antibody titres and seroconversion rate. [ Time Frame: Prior to the first dose of Cervarix (Day 0) and one month after the 3rd dose of Cervarix (Month 7). ]
  • Immunogenicity with respect to the components of Boostrix in terms of antibody concentrations. [ Time Frame: Prior to (Day 0) and one month after vaccination with Boostrix (Month 1). ]
  • Occurrence of solicited local and general symptoms. [ Time Frame: During Days 0-6 following vaccination with MenACWY-TT, Boostrix or the first dose of Cervarix. ]
  • Occurrence of unsolicited adverse events. [ Time Frame: During Days 0-30 following vaccination with MenACWY-TT, Boostrix or the first dose of Cervarix. ]
  • Occurrence of serious adverse events. [ Time Frame: Up to 8 months after the first vaccination. ]
  • Occurrence of new onset of chronic illness(es) (NOCIs) and Potential immune-mediated diseases (pIMDs). [ Time Frame: Up to 8 months after the first vaccination. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Infections, Meningococcal
Intervention  ICMJE
  • Biological: Meningococcal vaccine GSK134612
    One dose administered intramuscularly (IM) in the deltoid of the right arm.
    Other Name: Nimenrix®
  • Biological: Cervarix®
    Three doses administered intramuscularly (IM) in the deltoid of the left arm.
  • Biological: Boostrix®
    One dose administered intramuscularly (IM) in the deltoid of the left arm.
Study Arms  ICMJE
  • Experimental: Nimenrix+Cervarix (1,2,7-Month) Group
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 1, Month 2 and Month 7. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Interventions:
    • Biological: Meningococcal vaccine GSK134612
    • Biological: Cervarix®
  • Experimental: Nimenrix+Cervarix (0,1,6-Month) Group
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Interventions:
    • Biological: Meningococcal vaccine GSK134612
    • Biological: Cervarix®
  • Experimental: Cervarix Group
    Subjects in this group received 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6, administered intramuscularly (IM) in the deltoid region of the arm.
    Intervention: Biological: Cervarix®
  • Experimental: Nimenrix+Cervarix+Boostrix Group
    Subjects in this group received 1 dose each of Nimenrix and Boostrix vaccines at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. All vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Interventions:
    • Biological: Meningococcal vaccine GSK134612
    • Biological: Cervarix®
    • Biological: Boostrix®
  • Experimental: Boostrix+Cervarix Group
    Subjects in this group received 1 dose of Boostrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Interventions:
    • Biological: Cervarix®
    • Biological: Boostrix®
Publications * Rivera L, Chanthavanich P, Põder 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 19, 2012)
1300
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 29, 2014
Actual Primary Completion Date April 29, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 9 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Dominican Republic,   Estonia,   Thailand
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT01755689
Other Study ID Numbers  ICMJE 113823
2012-001876-13 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP