A Phase 1 First-in-Human Study (B4901001) Evaluating a Novel Anti-IgE Vaccine in Adult Subjects with Allergic Rhinitis

Rationale: Omalizumab, a monoclonal antibody against human IgE, is effective in the treatment of moderate to severe allergic asthma and chronic idiopathic urticaria. A vaccine inducing anti-IgE antibodies has the potential for similar clinical benefits with less frequent dosing and lower costs. We developed a vaccine antigen with two IgE peptide conjugates that target the same IgE constant domain 3 (CƐ3) as omalizumab, plus a different loop on CƐ3. A mouse mimetic vaccine was able to lower IgE production and demonstrate efficacy in prophylactic and therapeutic murine allergy models.

Methods: This was a randomized within cohort (total planned n=189 subjects), double-blinded, placebo controlled, dose ascending study to evaluate the safety, tolerability, immunogenicity and exploratory pharmacodynamic responses of the vaccine antigens (6, 20, 60 or 200 μg total) combined with fixed adjuvant doses of either aluminum hydroxide (0.5 mg) [IGE-1, PF-06444753] or aluminum hydroxide plus TLR9 agonist CpG 24555 (0.5 mg each) [IGE-2, PF-06444752]. Subjects received four study vaccinations at 0, 4, 8 and 24 weeks, then were followed for an additional 24 weeks.

Results: Both anti-IgE vaccines were tolerated well with regards to adverse events, local and systemic reactions, laboratory results, and other safety parameters. Anti-IgE antibodies were induced in an antigen dose-dependent manner, but there was no significant benefit with CpG included. Modest lowering of serum IgE levels was seen in some subjects. 

Conclusions: This novel anti-IgE vaccine was generally well-tolerated and induced anti-IgE specific antibodies, but did not lead to significant lowering of serum IgE in the majority of subjects.