Study in Adolescents/Adults to Evaluate Non-inferiority&Persistence up to 5 Years of GSK Bio MenACWY Conjugate Vaccine

Phase IIb Primary Vaccination Study to Evaluate Non-Inferiority & Persistence of the Immune Response of GSK Biologicals' MenACWY Conjugate Vaccine (Intramuscularly) vs Mencevax ACWY (Subcutaneously) to Healthy Subjects (11-55 Years of Age)

Meningococcal disease is mostly caused by N. meningitidis of serogroups A, B, C, W-135, Y. Meningococcal polysaccharide-conjugate vaccines have the advantage to induce a T-cell dependant immune response while the existing polysaccharide vaccines induce a T-cell independent response, i.e. with no immune memory response. GSK Biologicals has developed a combined Men ACWY conjugate vaccine intended to protect against meningococcal disease due to serogroups A, C, W-135 and Y. In the vaccination phase of this study, the new MenACWY-TT conjugate vaccine will be evaluated in adolescents and adults using Mencevax™ ACWY as control. In the long-term follow-up phase (extension phase) of the study, the long-term protection offered by the new MenACWY-TT conjugate vaccine will be assessed up to five years after the vaccination in adolescents and adults using Mencevax™ ACWY as control. This protocol posting deals with objectives & outcome measures of both the primary & extension phases.

Study Overview

• Status: Completed
• Conditions: Infections, Meningococcal
• Intervention / Treatment: Biological: Mencevax™ ACWY; Biological: meningococcal ACWY (vaccine)

Detailed Description

All subjects will have 7 blood samples taken: prior to and one month after vaccination and one, two, three, four and five years after vaccination. No new subjects will be enrolled in the extension phases of this Phase IIb study.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Manila, Philippines, 1000
    • GSK Investigational Site
  • Muntinlupa, Philippines, 1781
    • GSK Investigational Site
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that they and/or their parents/ legally acceptable representative can and will comply with the requirements of the protocol.
• A male or female between, and including, 11 and 55 years of age at the time of vaccination.
• Written informed consent obtained from the subject/ from the parent or legally acceptable representative of the subject.
• Free of obvious health problems 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 and/or his/her parents/legally acceptable representative's knowledge.
• If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, and must agree to continue such precautions for two months after completion of the vaccination series. Female subjects in childbearing potential who are not abstinent must have a negative pregnancy test.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the dose of vaccine(s).
• Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C W and/or Y within the last five previous years.
• Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C W and/or Y.
• History of meningococcal disease due to serogroup A, C, W or Y.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• History of Guillain-Barré syndrome.
• 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 study period.
• Pregnant or lactating female.
• History of chronic alcohol consumption and/or drug abuse.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Specific criteria to be checked at each study visit for the long term follow-up:

• History of meningococcal serogroup A,C, W and Y disease.
• Administration of a meningococcal polysaccharide or a meningococcal polysaccharide conjugate vaccine not planned in the protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimenrix Group; Subjects receiving GSK Biologicals' meningococcal vaccine 134612	Biological: meningococcal ACWY (vaccine); One intramuscular dose.
Active Comparator: Mencevax Group; Subjects receiving Mencevax™ ACWY	Biological: Mencevax™ ACWY; One subcutaneous dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine Response to Meningococcal Antigens for Serum Bactericidal Assay Using Rabbit Complement (rSBA)	Response to vaccine antigen was defined as: for initially seronegative subjects [subjects with serum bactericidal assay using rabbit complement (rSBA) titer lower than (<) 1:8, post-vaccination rSBA titer greater than or equal to (≥) 1:32] and for initially seropositive (subjects with rSBA titer ≥ 1:8), at least 4-fold increase in rSBA titer from pre to post vaccination.	One month post vaccination
Occurrence of Any Grade 3 Systemic Symptoms	Local symptom, Grade 3 = pain that prevented normal activity and redness/ swelling spreading beyond (>) 50 millimeters (mm). General symptom, Grade 3 = symptom that prevented normal activity and fever (orally) >39.5 °C.	During the 4-day (Days 0-3) post-vaccination period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitidis Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibody Titers ≥ the Cut-off Value	The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and (≥) 1:128.	Prior to and 1 Month after vaccination
rSBA Antibody Titers	Antibody titers are presented as Geometric Mean Titers (GMTs).	Prior to and 1 Month after vaccination
Number of Subjects With Anti-Polysaccharide (Anti-PS) Antibodies	The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 micrograms per milliliter (μg/mL) and ≥ 2.0 μg/mL.	Prior to and 1 Month after vaccination
Concentration of Anti-PS Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in micrograms/milliliter (µg/mL).	Prior to and 1 Month after vaccination
Number of Subjects With Anti-Tetanus (Anti-TT) Antibodies	Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).	Prior to and 1 Month after vaccination
Concentration of Anti-TT Antibodies	Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL).	Prior to and 1 Month after vaccination
Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value	The cut-off value for the rSBA titres was greater than or equal to (≥) 1:8 and ≥ 1:128.	At Year 1
rSBA Antibody Titers	Antibody titers are presented as Geometric Mean Titers (GMTs).	At Year 1
Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value	The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128.	At Year 2
rSBA Antibody Titers	Antibody titers are presented as Geometric Mean Titers (GMTs).	At Year 2
Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value	The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128.	At Year 3
rSBA Antibody Titers	Antibody titers are presented as Geometric Mean Titers (GMTs).	At Year 3
Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value	The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128.	At Year 4
rSBA Antibody Titers	Antibody titers are presented as Geometric Mean Titers (GMTs).	At Year 4
Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value	The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128.	At Year 5
rSBA Antibody Titers	Antibody titers are presented as Geometric Mean Titers (GMTs).	At Year 5
Number of Subjects With Anti-PS Antibodies	The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 μg/mL and ≥ 2.0 μg/mL.	At Year 1
Concentration of Anti-PS Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in µg/mL.	At Year 1
Number of Subjects With Anti-PS Antibodies	The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 μg/mL and ≥ 2.0 μg/mL.	At Year 2
Concentration of Anti-PS Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in µg/mL.	At Year 2
Number of Subjects With Anti-PS Antibodies	The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 micrograms per milliliter (μg/mL) and ≥ 2.0 μg/mL.	At Year 3
Concentration of Anti-PS Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in µg/mL.	At Year 3
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 50 millimeters (mm) of injection site.	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were fatigue, fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache. 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.	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects With New Onset of Chronic Illnesses (NOCIs)	NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.	From Day 0 up to 6 Months after vaccination
Number of Subjects With Rash		From Day 0 up to 6 Months after vaccination
Number of Subjects With AEs Resulting in Emergency Rooms Visits		From Day 0 up to 6 Months after vaccination
Number of Subjects With Unsolicited AEs	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.	Up to 31 Days after vaccination
Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	From Day 0 up to 6 Months after vaccination
Number of Subjects With SAEs	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	At Year 1, Year 2, Year 3, Year 4 and Year 5

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Borja-Tabora CF, Montalban C, Memish ZA, Boutriau D, Kolhe D, Miller JM, Van der Wielen M. Long-term immunogenicity and safety after a single dose of the quadrivalent meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine in adolescents and adults: 5-year follow-up of an open, randomized trial. BMC Infect Dis. 2015 Oct 6;15:409. doi: 10.1186/s12879-015-1138-y.
• Borja-Tabora C, Montalban C, Memish ZA, Van der Wielen M, Bianco V, Boutriau D, Miller J. Immune response, antibody persistence, and safety of a single dose of the quadrivalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine in adolescents and adults: results of an open, randomised, controlled study. BMC Infect Dis. 2013 Mar 5;13:116. doi: 10.1186/1471-2334-13-116.

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): December 23, 2006
• Primary Completion (Actual): September 7, 2007
• Study Completion (Actual): February 28, 2008

Study Registration Dates

• First Submitted: July 25, 2006
• First Submitted That Met QC Criteria: July 25, 2006
• First Posted (Estimate): July 26, 2006

Study Record Updates

• Last Update Posted (Actual): July 3, 2018
• Last Update Submitted That Met QC Criteria: June 5, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Healthy; Immunogenicity; Persistence; Meningococcal vaccine; Non-inferiority; Meningococcal A C W Y Diseases; meningococcal serogroups A, C, W & Y diseases
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections
• Other Study ID Numbers: 107386; 107392 (Ext: Y1) (Other Identifier: GSK); 107398 (Ext: Y2) (Other Identifier: GSK); 107402 (Ext: Y3) (Other Identifier: GSK); 107404 (Ext: Y4) (Other Identifier: GSK); 107406 (Ext: Y5) (Other Identifier: GSK)

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. Clinical Study Report
   Information identifier: 107386
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 107386
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 107386
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 107386
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 107386
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 107386
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register