Comparison of GSK134612 in Subjects Previously Vaccinated Against Meningococcal Disease Versus Non-vaccinated Subjects

Immunogenicity & Safety Study of GSK Biologicals' Meningococcal Vaccine GSK134612 Administered in Healthy Subjects Either Previously Primed With Mencevax™ ACWY or naïve to Meningococcal Vaccination.

In this study, subjects who were vaccinated with a meningococcal polysaccharide vaccine in a previous study (whose objectives & outcome measures are presented in a separate protocol posting with NCT number = 00227422) will be vaccinated with a new vaccine using conjugation technology.

These subjects will be compared to subjects vaccinated with the new vaccine, but who were not previously vaccinated with a meningococcal polysaccharide vaccine.

Study Overview

• Status: Completed
• Conditions: Infections, Meningococcal
• Intervention / Treatment: Biological: Meningococcal vaccine GSK134612 (Nimenrix)

Detailed Description

GSK Biologicals has developed a meningococcal conjugate vaccine (GSK134612). This candidate vaccine has been shown to be well tolerated and immunogenic in toddlers, children aged 3-5 years, and adolescents/young adults. Repeated vaccinations with unconjugated meningococcal polysaccharide vaccine has shown to induce hyporesponsiveness to re-vaccination, this for serogroup C, and a recent publication suggest the same may be true for other serogroups.

This study will evaluate GSK Biologicals' candidate vaccine's ability to induce satisfactory immune response for the serogroups it contains across subjects 4.5 through 34 years of age who previously received a tetravalent meningococcal polysaccharide vaccine when aged 2-30 years. A non-randomised age-strata matched group of subjects, who have not previously received (or not received within the preceding 10 years) any meningococcal vaccine, will also be administered the GSK134612 vaccine for comparison.

• Study Type: Interventional
• Enrollment (Actual): 271
• Phase: Phase 2

Contacts and Locations

Study Locations

• Lebanon
  • Beirut, Lebanon, 1107-2020
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 34 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Only subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
• For the MPS group, a male or female between, and including, 4.5 and 34 years of age at the time of the study vaccination, who has been vaccinated in GSK Biologicals' study 102394.
• For the noMPS group, a male or female between, and including, 4.5 and 34 years of age at the time of the study vaccination.
• Written informed consent obtained from the subject/ from the parent or guardian of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Previously completed routine childhood vaccinations to the best of his/her knowledge.
• If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding administration of the study vaccine, or planned use during the complete study period (active phase and extended safety follow-up).
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the study vaccine dose.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of administration of the study vaccine and up to 30 days after the study vaccine.
• Concurrently participating in another clinical study, at any time during the study period (active phase and extended safety follow-up), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• For the MPS Group, vaccination against meningococcal disease after completion of study 102394
• For the noMPS group, previous vaccination, or vaccination within the last 10 years, against meningococcal disease (of any serogroup).
• Previous vaccination against tetanus within 30 days.
• History of meningococcal disease.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and physical.
• A family history of congenital or hereditary immunodeficiency, unless the child has previously been documented, through laboratory testing, to have normal immune function.
• History of reactions or allergic disease likely to be exacerbated by any component of the vaccine.
• Know hypersensitivity to any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease.
• Acute disease 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 active stage of the study period.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of chronic alcohol consumption and/or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mencevax Primed Group; Subjects who were previously vaccinated with meningococcal vaccine Mencevax ACWY in study NCT00227422 received in the current study a single dose of meningococcal conjugate vaccine Nimenrix, administered intramuscularly in the deltoid muscle of the non-dominant arm.	Biological: Meningococcal vaccine GSK134612 (Nimenrix); one dose, as intramuscular injection
Active Comparator: Mencevax Naive Group; Subjects who did not receive (or had not received in the preceding 10 years) any meningococcal vaccination received in the current study a single dose of meningococcal conjugate vaccine Nimenrix, administered intramuscularly in the deltoid muscle of the non-dominant arm.	Biological: Meningococcal vaccine GSK134612 (Nimenrix); one dose, as intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meningococcal Serum Bactericidal Antibodies/Assay (rSBA) Titers	For each antibody assessed (serogroups A, C, W, and Y) at the corresponding time point, titers were expressed as geometric mean titers (GMTs) and tabulated with 95% confidence intervals (CIs).	One month post-vaccination (Month 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meningococcal rSBA Titers	For each antibody assessed (serogroups A, C, W, and Y) at the corresponding time point, titers were expressed as geometric mean titers (GMTs) and tabulated with 95% confidence intervals (CIs).	Prior to vaccination (Day 0)
Anti-meningococcal Polysaccharide (PS) Antibody Concentrations	For each antibody assessed (serogroups A, C, W, and Y) at the corresponding time point, polysaccharide antibody concentrations were expressed as geometric mean concentrations (GMCs) in micrograms per milliliter (µg/mL) and tabulated with 95% confidence intervals (CIs).	Prior to (Day 0) and one month post-vaccination (Month 1)
Anti-tetanus Toxoid Antibody Concentrations	Antibody concentrations were tabulated as geometric mean concentrations (GMCs) in International Units per milliliter (IU/mL), with 95% confidence intervals (CIs).	Prior to (Day 0) and one month post-vaccination (Month 1)
Number of Subjects With a Vaccine Response to Meningococcal Antigens A, C, W and Y	Vaccine response defined as: For initially seronegative subjects: post-vaccination antibody titer ≥1:32 For initially seropositive subjects: post-vaccination antibody titer ≥4-fold the pre-vaccination antibody titer	One month post-vaccination (Month 1)
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 = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.	During the 4-day (Day 0 to Day 3) period after vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Day 0 to Day 3) period after vaccination
Number of Subjects With Unsolicited Symptoms	An unsolicited symptom 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 symptom regardless of intensity grade or relation to vaccination.	Up to one month post-vaccination (Month 1)
Number of Subjects Reporting Any Serious Adverse Events	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	Day 0 to study month 6
Number of Subjects With Any Specific Adverse Events	Specific adverse events comprised rash, new onset of chronic illnesses (NOCIs), conditions prompting emergency room (ER) visits and/or any event related to lack of vaccine efficacy (i.e. documented meningococcal disease). Events related to lack of vaccine efficacy (i.e. meningococcal disease) were recorded, but because such events were life threatening and were thus reported as SAEs, these events were not analyzed or reported here separately.	Day 0 to study month 6

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Dbaibo G, Van der Wielen M, Reda M, Medlej F, Tabet C, Boutriau D, Sumbul A, Anis S, Miller JM. The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine. Int J Infect Dis. 2012 Aug;16(8):e608-15. doi: 10.1016/j.ijid.2012.04.006. Epub 2012 Jun 14.
• Dbaibo G et al. One dose of the meningococcal tetravalent tetanus toxoid conjugated vaccine (MenACWY-TT) is immunogenic with an acceptable safety profile in unvaccinated subjects and those previously vaccinated with a MenACWY polysaccharide vaccine. Abstract presented at the 3rd Northern European Conference on Travel Medicine (NECTM). Hamburg, Germany, 26-29 May 2010.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2008
• Primary Completion (Actual): December 19, 2008
• Study Completion (Actual): December 19, 2008

Study Registration Dates

• First Submitted: April 14, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimate): April 18, 2008

Study Record Updates

• Last Update Posted (Actual): December 28, 2018
• Last Update Submitted That Met QC Criteria: June 21, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Safety; immunogenicity; Meningococcal disease; Booster vaccination; Meningococcal vaccine
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections
• Other Study ID Numbers: 107408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 107408
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register