CONJUNCTIVAL PROVOCATION TESTING IN A DOSE FINDING STUDY WITH SUBCUTANEOUS IMMUNOTHERAPY WITH GRASS + MPL

Abstract

Introduction The total symptom score (TSS) measured during conjunctival provocation testing (CPT) was used as primary endpoint of a Phase II study to evaluate the dose response for a subcutaneous immunotherapy (SCIT) product (1.0 ml) with modified allergen tyrosine adsorbate (MATA) and monophosphoryl lipid A (MPL) adjuvants developed for treatment of allergic rhinoconjunctivitis due to grass pollen [EudraCT 2017-000333-31]. Doses of 5100, 14400, 27600 and 35600 standardized units (SU) and placebo were evaluated. Methods CPTs were performed at screening, pre-dose and approximately 4 weeks post-treatment. TSS was calculated as the sum of 4 symptoms (eye redness, tearing, itching and irritation), each scored on a 4-point scale. Concentrations of 0.3, 1.0, 3.0, 10 and 30 Histamine Equivalent Potency units (HEP)/mL were available for testing. A TSS ≥ 6 points was required at screening and pre-dose. Results The blinded results showed a mean TSS of 7.5 (95% CI: 7.3-7.6) and 4.4 points (95% CI: 4.2-4.7) at pre-dose and post-treatment, respectively. For 251 patients of the 426 patients (58.9%) a positive post-treatment CPT was achieved at least one higher concentration of allergen compared to pre-dose. Conclusions In this Phase II study, CPT was used to establish a dose response of a grass MATA MPL SCIT product using a wide range of cumulative dose regimens. The blinded results indicate adequate CPT performance which may well support the selection of the optimal dose for Phase III, which would be an important milestone in the development of an efficacious and safe pre-seasonal state-of-the-art grass SCIT.