Immunogenicity and Safety of Group A, C, Y & W-135 Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine

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
seroconversion, which is defined as a 4-fold rise in Serum Bactericidal Antibody (SBA)
titer, four weeks after injection. The number and proportion of subjects achieving
seroconversion 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.

Inclusion Criteria:

- Participant is willing and able to give informed consent and comply with all aspects
of the evaluation after the nature of the study is explained.

- Male or female, aged 18 to 55 years old

- In general good health with no significant chronic or acute conditions that would
interfere with immune response or expected AE evaluation in the opinion of the
investigator as determined by Medical history and/or History-directed physical
examination

- Abstinence or use of effective contraception by the participants or their partners
during the trial and continuing for four weeks after vaccination will be required for
males or female participants of child bearing potential.

- Able (in the opinion of the investigator) to comply with all study requirements.

Exclusion Criteria:

- Unwilling or unable to understand study requirements and give written informed
consent for the study.

- Prisoners.

- History of Guillain-Barré syndrome (GBS).

- Pregnancy (confirmed by positive pregnancy test) or lactation.

- Previous diagnosis of laboratory confirmed meningococcal disease.

- Previous meningococcal meningitis vaccination in the last five years

- Laboratory abnormalities that are considered Grade 2 or higher (based on AE, ranges
as described in the protocol appendix) that in the opinion of the Investigator would
raise safety concerns for participation in the study or interfere with evaluation of
study objectives, or abnormalities >2X ULN.

- Known or suspected autoimmune or connective tissue disorders, including rheumatoid
arthritis and congenital or acquired immunodeficiency. Does not include mild to
moderate seasonal/perennial allergies treated with over the counter antihistamines.

- Use of systemic immunosuppressive drugs or therapy within 6 months prior to study
enrollment, not including topical or inhaled steroids/cytotoxic agents. Includes
anti-cancer chemotherapy, radiation, and long term systemic corticosteroid therapy.
History of anaphylactic shock, severe asthma, urticaria, or other allergic or
hypersensitivity reactions following vaccination or known hypersensitivity to any
vaccine component.

- Received blood, blood products, plasma derivatives or any parenteral immunoglobulin
preparation in the past 3 months.

- Use of systemic antibiotics within 72 hours prior to study enrollment.

- History of cirrhosis or hepatitis.

- Known bleeding disorder or condition associated with a prolonged bleeding time.

- Positive results of testing for HepBsAg, Hepatitis C or HIV-1 or HIV-2 antibodies.
Known or suspected HIV or Hepatitis B or C infection.

- Positive results of drug screen that cannot be explained by use of approved
prescription medication (amphetamine, THC, cocaine). Current (past 30 days) heavy
smokers (greater than or equal 1 pack per day).

- Received another investigational product within the last 30 days. Investigational
product may be a drug, vaccine, medical device or medical procedure.

- History of significant head trauma, alcohol or substance abuse or other medical
illnesses that could cause a neurological deficit (e.g., cerebro-vascular disease).

- Medication or alcohol use that, in the opinion of the Investigator, may influence or
bias the clinical outcome of the trial.

- History of any serious chronic medical or psychiatric illnesses or condition which,
in the opinion of the investigator, might interfere with the evaluation of the study
objectives.

- History of chronic or severe headaches, myalgia, arthralgia, malaise, fatigue or
other systemic disorder commonly observed as AEs for licensed meningococcal vaccines.

- Currently experiencing a cold, flu or other acute illness (subject may be deferred
until after recovery).