Immunogenicity and Safety of Group A, C, Y & W-135 Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine
Condition: Meningococcal Meningitis; Meningococcal Infections
MeSH terms: Diphtheria; Meningococcal Infections; Meningitis, Meningococcal; Meningitis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the production of antibodies to a new conjugate
      vaccine, NmVac4-A/C/Y/W-135-DT, as a measure of vaccine effectiveness, compared to the
      production of antibodies to a similar, licensed meningococcal (Groups A, C, Y, W-135)
      polysaccharide diphtheria toxoid (DT) conjugate vaccine. The investigators will also evaluate
      the safety of NmVac4-A/C/Y/W-135-DT™ conjugate vaccine compared to the licensed vaccine. The
      hypothesis is that the test vaccine is comparable to the licensed active control vaccine.
    

Detailed description: 
      Meningococcal disease is a potentially life-threatening bacterial infection. The disease most
      commonly is expressed as either meningococcal meningitis, an inflammation of the membranes
      surrounding the brain and spinal cord, or meningococcemia, the presence of bacteria in the
      blood. The most common symptoms include high fever, headache, neck stiffness, confusion,
      nausea, vomiting, lethargy, and rash. If not treated the disease can progress rapidly and can
      lead to shock and death, often within hours of the onset of symptoms. The disease is fatal at
      a rate of 10%. Of patients who recover, 10% have permanent hearing loss or other serious
      sequelae.

      Neisseria meningitidis capsular polysaccharides are poor immunogens. However, conjugation of
      bacterial polysaccharides to immunogenic carrier proteins generally results in conjugates
      that induce strong anti-polysaccharide T-helper cell dependent immune responses, creating a
      longer-lasting immune response and thus protection against meningococcal infection.

      The sponsor's small size Phase 1 clinical trial comprised 60 subjects. Therefore, additional
      data is needed to confirm the previous data with a statistically powered Phase 2 clinical
      trial. The present study aims to evaluate subject responses to single doses, administered in
      adult subjects, to determine further safety and immunogenicity of the vaccine. This study
      compares safety and antibody production induced by one intramuscular injection of either
      NmVac4-A/C/Y/W-135-DT or a licensed meningococcal (Groups A, C, Y, W-135) polysaccharide
      diphtheria toxoid conjugate vaccine. The primary immunogenicity endpoint will be
      seroresponse, based on antibody titer ≥1:8 for subjects with titer <1:8 at baseline or a
      4-fold rise in antibody levels, 4 weeks after a single injection . The number and proportion
      of subjects achieving seroresponse will be tabulated by serogroup for each vaccine group. A
      non-inferiority test will be used to determine if the immune response elicited by NmVac4
      A/C/Y/W-135-DT™ is not less than a specified difference in percent seroconversion from the
      licensed control vaccine. Participants will attend a screening visit up to 6 weeks prior to
      vaccination (day 0), then will attend study visits for 4 weeks. There will be a study phone
      call at days 2-3, then a post-study call to subjects to assess safety at 26 weeks.
    

Intervention name(s): Test Vaccine; US Licensed Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): NmVac4-A/C/Y/W-135-DT™ conjugate is a vaccine in liquid form composed of purified polysaccharides (PS) conjugated to diphtheria toxoid. Single intramuscular 0.5 mL dose contains 4 µg each of Serogroup A, C, W-135, and Y PS conjugated to approximately 26 µg total diphtheria toxoid.; Meningococcal (Groups A,C,Y,W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine 0.5 mL dose, intramuscular. Single dose contains 4 µg each Serogroup A, C, W-135 and Y conjugated to approximately 48 µg total diphtheria toxoid.
Other intervention name(s): meningococcal meningitis conjugate vaccine, quadrivalent; NmVac4-A/C/Y/W-135-DT™; meningococcal meningitis conjugate vaccine, quadrivalent
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Central Nervous System Infections; Meningitis; toxoid; Meningococcal vaccine; conjugate vaccines