Understanding the Immune Response to Meningitis Vaccines

NCT00901940 | Completed Phase 3

• 1 other identifier: 2007/04
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate and compare the immune response to two vaccines against 4 related bacteria: meningococcal serogroups A, C, W-135 and Y. These bacteria can cause meningitis and /or septicaemia (blood poisoning). The two vaccines are a protein-polysaccharide conjugate vaccine (MenACWY)and a meningococcal plain polysaccharide vaccine(MenACWY PS). Both vaccines are licensed and are currently used for travellers to areas with a high incidence of invasive meningococcal disease. However, plain polysaccharide vaccines are known to be poorly immunogenic in children and they do not stimulate immunological memory, apart from the serogroup A component. In contrast, a protein-polysaccharide conjugate vaccine against meningococcal serogroups A, C, W-135 and Y has been found to be immunogenic in infants and to be able to induce immunological memory. The proposed study is a single centre, open-label, randomised, controlled study in 150 healthy adults aged 18-70 years. The participants will be given either 2 injections of the meningococcal protein-polysaccharide conjugate vaccine one month apart, or one injection of the meningococcal plain polysaccharide vaccine followed one month later with an injection of the meningococcal conjugate vaccine. Blood samples will be collected before immunisation and at several time points following immunisations to evaluate the level of meningococcal specific antibody induced by two different vaccination regimes. The data derived from the study will be relevant in determining which of these vaccines should be used in preference in travellers who are receiving immunisation against meningococcal disease before travelling to high risk areas. Additionally, a number of scientific questions regarding the nature of the immune response to the two vaccines (specifically looking at the white blood cells responsible for producing antibodies, known as B cells) and the role of genetic variations in influencing the vaccine recipient's immune response will be addressed in the study.

Conditions

Meningitis; Septicemia

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be whether the SBA GMT at day 7 following MenACWY is ≥ 30% greater than that observed at day 7 following MenACWY PS.

  Day 7

Secondary Outcomes (5)

• The measurement of meningococcal serogroup C SBAs (using human complement) at day 7 following the initial immunisation with MenACWY and MenACWY PS.

  Day 7

• The measurement of meningococcal serogroup A and C specific SBAs (using human complement) at day 28 following the initial immunisation with MenACWY and MenACWY PS, and at day 7 and day 28 following the 'follow up' immunisation with MenACWY.

  Day 7-28

• Meningococcal serogroup W-135 and Y SBAs will also be performed on a subset of samples obtained at the above timepoints.

  Day 7-28

• The measurement of meningococcal serogroup A, C, W-135 and Y specific memory B cells and plasma B cells at day 7, and memory B cells at day 28 after first immunisation with MenACWY and MenACWY PS, and after the 'follow up' immunisation with MenACWY.

  Day 7-56

• Other assessments of the immune response to MenACWY and MenACWY PS (e.g. measurement of meningococcal serogroup A, C, W-135 and Y specific IgG by ELISA) may also be performed.

  Day 7-56

Study Arms (2)

MenACWY Plain Polysaccharide (ACWY Vax)

ACTIVE COMPARATOR

The MenACWY Plain Polysaccharide Vaccine, which is already licensed and is used as a travel vaccine, is known as the MenACWY plain polysaccharide (ACWY Vax). Participants in this arm will receive 1 dose of the MenACWY plain polysaccharide (ACWY Vax) and 1 dose of the MenACWY conjugate (MenACWY).

Biological: Meningococcal polysaccharide A, C, Y and W135 and Menveo

MenACWY conjugate

ACTIVE COMPARATOR

The MenACWY conjugate vaccine was licensed in the UK in March 2010, and is known as the MenACWY conjugate vaccine (Menveo). Participants in this arm will receive 2 doses of the MenACWY conjugate vaccine.

Biological: Meningococcal (Groups A, C, Y and W-135) Conjugate

Interventions

Meningococcal (Groups A, C, Y and W-135) Conjugate BIOLOGICAL

2 x 0.5 mL dose

Also known as: MenACWY, Menveo

MenACWY conjugate

Meningococcal polysaccharide A, C, Y and W135 and Menveo BIOLOGICAL

1 x 0.5 mL dose of ACWY Vax, 1 x 0.5 mL dose of Menveo

Also known as: ACWY Vax, Menveo

MenACWY Plain Polysaccharide (ACWY Vax)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent for participation after the nature of the study has been explained
• Male or Female, aged 18- 70 years inclusive
• In good health as determined by:
• Medical history
• History-directed physical examination
• Clinical judgment of the investigator
• Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
• Able (in the Investigator's opinion) and willing to comply with all study requirements
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study

You may not qualify if:

• Are unwilling or unable to give written informed consent to participate in the study
• Have previously received any meningococcal vaccine (this will be confirmed with the participant's general practitioner after enrolment)
• Have previously been diagnosed with laboratory confirmed meningococcal disease
• Have a history of any anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component
• Have a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):
• Receipt of any immunosuppressive therapy
• Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroid therapy\* (\*prednisolone or equivalent for more than two consecutive weeks within the past 3 months).
• Have a suspected or known HIV infection or HIV related disease
• Have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months
• Have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time
• Have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
• Participation in another clinical trial investigating a vaccine, a drug, a medical device, or a medical procedure
• Pregnancy as confirmed by a positive pregnancy test
• Currently breast-feeding

Sponsors & Collaborators

• University of Oxford: lead
• Novartis Vaccines: collaborator

Study Sites (1)

University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine

Oxford, OX3 7LJ, United Kingdom

Location

Related Publications (1)

• Ramasamy MN, Clutterbuck EA, Haworth K, Bowman J, Omar O, Thompson AJ, Blanchard-Rohner G, Yu LM, Snape MD, Pollard AJ. Randomized clinical trial to evaluate the immunogenicity of quadrivalent meningococcal conjugate and polysaccharide vaccines in adults in the United kingdom. Clin Vaccine Immunol. 2014 Aug;21(8):1164-8. doi: 10.1128/CVI.00099-14. Epub 2014 Jun 25.

  PMID: 24964805 BACKGROUND

MeSH Terms

Conditions

Meningitis; Sepsis

Interventions

MenACWY; Meningococcal Vaccines; meningococcal group A polysaccharide

Condition Hierarchy (Ancestors)

Neuroinflammatory Diseases; Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Andrew Pollard, FRCPCH, PhD

  University of Oxford, Department of Paediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 13, 2009
• First Posted: May 14, 2009
• Study Start: June 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: December 5, 2014

Record last verified: 2014-06

Locations

GB (1)