A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy

Abstract

Background

A novel subcutaneous allergen immunotherapy formulation (gpASIT+^™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity, and safety.

Methods

This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170, or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3, and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks, and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.

Results

CPT response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP versus 25.6% of patients receiving placebo (modified per protocol set). Also, 39% of patients in the 170 μg-group became non-reactive to CPT versus 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG₄ levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg), and 3.9-fold (370 μg) (mPP).

Conclusion

Three-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

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