A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants

Vaccine. 2014 Sep 8;32(40):5206-11. doi: 10.1016/j.vaccine.2014.07.049. Epub 2014 Jul 29.

Abstract

Background: Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed.

Methods: This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase.

Results: Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0°C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose.

Conclusion: Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants.

Trial registration: ClinicalTrials.gov NCT00798304.

Keywords: Factor H-binding protein; Infants; LP2086; Neisseria meningitidis serogroup B.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions
  • Early Termination of Clinical Trials*
  • Female
  • Fever / chemically induced*
  • Humans
  • Infant
  • Male
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines / adverse effects*
  • Meningococcal Vaccines / therapeutic use
  • Neisseria meningitidis, Serogroup B
  • Single-Blind Method
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / therapeutic use

Substances

  • Meningococcal Vaccines
  • Vaccines, Synthetic

Associated data

  • ClinicalTrials.gov/NCT00798304