Phase 1 Safety and Immunogenicity of Meningococcal Vaccine

Meningococcal Infection, Group B

Meningococcal vaccine, Neisseria meningitidis

The purpose of this study is to determine whether a vaccine based on outer membrane vesicles (NOMV) from genetically detoxified group B meningococcus is safe and effective for use as a vaccine. If so, the NOMV in this vaccine will be combined with NOMV from two other genetically modified strains as a potentially globally effective vaccine against group B meningococcus.

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.

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