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

Abstract

BackgroundA 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.MethodsThis 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.ResultsConjunctival provocation test (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 vs 25.6% of patients receiving placebo (modified per‐protocol set). Also, 39% of patients in the 170‐μg group became nonreactive to CPT vs 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).ConclusionThree‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

Highlights and recent developments in airway diseases in EAACI journals (2018)

“…Recent studies confirmed AIT with grass allergen peptides (170 μg over 3 weeks) 110,111 and depigmented polymerized allergen extracts 112 as safe and effective treatments for local AR caused by grass pollen sensitization. A maximum cumulative dose of 490 μg of the grass pollen peptides was well tolerated with only a few minor adverse reactions.…”

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

“…213 Moreover, there is some evidence that AIT is cost-effective in AR with or without asthma. 214 Allergen-specific immunotherapy is usually given as subcutaneous injections 215,216 or sublingually, [217][218][219] but novel treatment forms such as peptide immunotherapy, 11,220 intralymphatic immunotherapy 11,220 and use of recombinant allergens, and immune-modulating adjuvants and nanoparticles 21,220,221 are under development.…”

“…[3][4][5][6][7][8] In addition, a number of promising small molecule drugs and vaccines are in the development pipeline. [9][10][11] This new era is now calling for the development of biomarkers and phenoand endotyping of diseases for customized patient care, which is termed stratified medicine, precision medicine, or personalized medicine. 4 Distinguishing phenotypes of a complex disease covers the observable clinically relevant properties of the disease but does not show a direct relationship to disease etiology and pathophysiology.…”

Development of subcutaneous allergen immunotherapy (part 2): preventive aspects and innovations

“…A further development, so-called adjuvant-free allergen peptide hydrolysate, also aims to achieve a high immunological effect with reduced IgE reactivity, [79], which has so far been demonstrated for a short duration of therapy of only three weeks [113]. The follow-up field study with these peptides on 554 grass pollen-allergic adults showed a significant but only moderate clinical advantage in the primary endpoint, as well as marked effects in the secondary endpoints investigated [114].…”