P300 EVALUATION OF DAILY PATCH APPLICATION DURATION FOR EPICUTANEOUS IMMUNOTHERAPY FOR PEANUT ALLERGY

Background: Epicutaneous immunotherapy (EPIT) for peanut allergy is a potential novel immunotherapy that utilizes the unique cutaneous immunologic properties to induce desensitization. A randomized, double-blind, placebo-controlled Phase 3 trial (PEPITES) in peanut-allergic children 4‐11 years demonstrated an epicutaneous patch (DBV712) with 250 µg peanut protein was statistically superior to placebo in inducing desensitization following 12 months of daily treatment. Objective: To investigate what baseline and in-study factors influenced response to DBV712 250 µg, with a focus on patch adhesion, by posthoc analysis of PEPITES data. Methods: A posthoc multivariate model built with log-transformed Month 12 eliciting dose (ED) as the dependent variable was used to assess the influence of baseline characteristics and patch adhesion. Baseline characteristics and treatment response were also evaluated by stratifying subjects into decile subgroups by patch detachment rates over the 12-month study. Results: Multivariate analysis identified higher baseline ED and lower baseline peanut-specific IgE as the variables most predictive of higher Month 12 ED, followed by mean daily patch application duration, baseline SCORing Atopic Dermatitis (SCORAD) score, and age. By decile stratification, no association between patch detachment and treatment response was identified for 80% of DBV712-treated subjects. All DBV712-treated subjects, including those with the highest patch detachment rates, demonstrated treatment benefit measured by fold-changes in geometric mean ED. Conclusion: We identified subject baseline characteristics of higher baseline ED and lower baseline peanut-specific IgE as most predictive of higher Month 12 ED. For the majority of treated subjects, patch detachment did not impact treatment response. A minority of subjects, highly sensitive to peanut at baseline, had lower prespecified responder rates and higher patch detachment rates, yet still benefited from treatment based upon fold-changes in ED.

Download Full-text

Evaluation of daily patch application duration for epicutaneous immunotherapy for peanut allergy

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200045 ◽

2020 ◽

Vol 41 (4) ◽

pp. 278-284

Author(s):

David M. Fleischer ◽

Jonathan M. Spergel ◽

Edwin H. Kim ◽

Dianne E. Campbell ◽

Todd D. Green ◽

...

Keyword(s):

Clinical Trial ◽

Peanut Allergy ◽

Response Rate ◽

Peanut Protein ◽

Phase Iii ◽

Application Time ◽

Phase Iii Clinical Trial ◽

Patch Application ◽

Epicutaneous Immunotherapy ◽

Post Hoc

Background: Epicutaneous immunotherapy is a potential novel immunotherapy that utilizes unique cutaneous immunologic properties. In a phase III, randomized, double-blind, placebo controlled clinical trial, an epicutaneous patch (DBV712) with 250 µg of peanut protein applied once daily for 12-months was statistically superior to placebo in desensitizing children with peanut allergy (ages 4‐11 years) (N = 356). Objective: To assess the relationship between the hours of daily application time and the efficacy of DBV712 250 µg. Methods: DBV712 250 µg was applied to 30 nonallergic volunteers for various durations from 2 to 24 hours and then assayed for residual peanut protein. Patch application data from the phase III clinical trial were analyzed post hoc according to prespecified responder rates and changes in the eliciting dose (ED), as measured by the geometric mean (GM) ED ratio (12 months/baseline). Results: Following application, there was a marked decrease in peanut protein on the patches from 2 to 12 hours. After 12 hours, the median peanut protein recovered was below quantification limits. The median daily patch application duration in subjects from the phase III clinical trial was 21.1 hours (DBV712 250 µg) and 22.4 hours (placebo). Ninety-five percent of the treated population achieved >10 hours per day mean application. Response rates and GM ED ratios were similar among subjects across a range of application durations; e.g., in those with a mean duration of >10 hours, the response rate was 36.6% and the GM ED ratio was 3.8, comparable with 42.6% and 4.0, respectively, in those with a mean duration of >20 hours. In DBV712 250 µg subjects with >16 hours mean application duration (84.5% of the treated population), the response rate was 38.8% versus 13.4% for placebo (difference, 24.4% [95% confidence interval, 15.5‐34.0%]; p < 0.001). Conclusion: An evaluation of residual peanut protein on patches following application and post hoc analysis of phase III data strongly suggest that allergen delivery is attained with 12‐16 hours of daily patch application time, sufficient to drive clinically meaningful desensitization to peanut after 12 months.

Download Full-text