Phase 1 Safety and Immunogenicity of Meningococcal Vaccine

This was a Phase 1, outpatient, open-label, dose-escalating study to evaluate the safety,
tolerability, and immunogenicity of 4 doses of the Group B Meningococcal HOPS-G 8570 NOMV
vaccine in healthy subjects. Subjects were screened by medical history; physical exam;
complete blood count; serum chemistry profile; coagulation studies including prothrombin time
(PT), partial thromboplastin time (PTT), and fibrinogen; human immunodeficiency virus (HIV)
test, anti-hepatitis C virus (HCV) antibodies, and hepatitis B surface antigen (HBsAg) test
results; nasopharyngeal swabs for carriage of meningococci; bactericidal antibody titer to
meningococci; and urinalysis; and urine pregnancy test results for females. The first 36
subjects to meet all inclusion criteria and none of the exclusion criteria were assigned to 1
of 4 dosage groups of 9 subjects each. After screening, there was a 10 to 60 day lead-in time
(depending on when screening occurred) prior to vaccination during which subjects could not
take or receive any experimental products. Also prior to vaccination, adverse events were
recorded to establish a baseline with which to compare adverse events occurring after
vaccination. Subjects kept a diary for 7 days before the first dose and for 1 day before each
of the second and third doses. Immediately before each vaccination, vital signs were checked,
an abbreviated physical examination was performed, each subject's throat was swabbed to
assess carriage of meningococcal bacteria, and blood was drawn for immunology and safety
labs. Urine was collected for analysis and females took a urine pregnancy test. The pregnancy
test results had to be negative in order for a subject to be vaccinated. The vaccine with
adjuvant was given intramuscularly at 0, 6, and 12 weeks (Study Days 0, 42, and 84) in doses
of 10 μg, 25 μg, 50 μg, or 75 μg based on protein concentration. Vaccinations were performed
in a staggered fashion with safety monitoring between groups. The 10-μg dose group was
divided into 2 subgroups. Subjects in the first subgroup were vaccinated 30 minutes apart to
observe subjects for the occurrence of acute side effects, and subjects in the second
subgroup were vaccinated 1 week after the first. The subjects in each group were monitored
for AE for at least 2 weeks prior to vaccinating the next higher dosage group. Subjects were
kept in the Clinical Trials Center for 30 minutes after each vaccination for observation, and
they were asked to keep a diary of symptoms for 7 days after each vaccination. AEs and SAEs
were recorded at all study visits, and each AE or SAE was assessed for severity and
relationship to the vaccine by the investigator.

Inclusion Criteria:

- Healthy (by physical examination and medical history) military or civilian males or
females;

- Age 18-45 years;

- Able to give informed consent, understands risks and benefits of study, assents to use
of blood samples for future research; understands and is willing to comply with all
protocol procedures and time commitments;

- Females must have a negative urine pregnancy test on vaccination day before each dose
AND agree to practice an effective birth control method as necessary, for 6 months
after the first vaccination;

- Military service-members who wish to participate must obtain written permission from
their immediate supervisor, department chief or equivalent, and company commander or
equivalent.

Exclusion Criteria:

- Current or history of significant organ/system disease;

- History of allergy to any vaccine;

- History of allergy to aluminum hydroxide;

- Presence of significant unexplained laboratory abnormality that in the opinion of the
PI may potentially confound the analysis of the study results;

- HIV seropositive or any other immunosuppressive state;

- Positive test for HBsAg or hepatitis C antibody;

- Evidence or admission of on-going drug or alcohol abuse/dependence;

- Intention to leave the area during the study such that the volunteer would miss 1 or
more study days;

- Prior receipt of any group B meningococcal outer membrane protein (OMP) vaccine or a
vaccine containing meningococcal OMP;

- Has received or plans to receive any live vaccine, Investigational New Drug (IND)
products or significant immunosuppressive therapy* in the 28 days prior to, or any
inactivated vaccine within 14 days before initial vaccination or throughout the study,
or received parenteral immunoglobulin or blood products within 3 months of study
initiation;

- (Intra-articular, topical, or intranasal steroids, steroids applied to the eye,
or ≤ 7 days of oral steroids are in general acceptable, depending on the
formulation and condition for which they are prescribed. Inclusion of individuals
receiving these medications will be made by the PI on a case by case basis)

- High levels of baseline bactericidal antibodies against the vaccine strain on
screening (>1:16) and/or throat carriage of Neisseria meningitidis at time of
screening;

- Positive urine pregnancy test prior to vaccination;

- Lactation from first dose through 3 months after last dose;

- Any condition in the opinion of the investigator that might interfere with the study
vaccine.