Evaluation of daily patch application duration for epicutaneous immunotherapy for peanut allergy
| Autor: | David Fleischer, Edwin H. Kim, Terrance Ocheltree, Jonathan M. Spergel, Romain Lambert, Dianne E. Campbell, Hugh A. Sampson, T. Green, Katharine J Bee |
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| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult Male Time Factors Adolescent Population Peanut allergy Transdermal Patch medicine.disease_cause Placebo Administration Cutaneous 01 natural sciences 03 medical and health sciences Young Adult 0302 clinical medicine Allergen Post-hoc analysis medicine Immunology and Allergy Humans Peanut Hypersensitivity 0101 mathematics education Child Plant Proteins Randomized Controlled Trials as Topic education.field_of_study business.industry 010102 general mathematics General Medicine Allergens medicine.disease Confidence interval Healthy Volunteers Clinical trial 030228 respiratory system Clinical Trials Phase III as Topic Desensitization Immunologic Anesthesia Child Preschool Female Geometric mean business |
| Zdroj: | Allergy and asthma proceedings. 41(4) |
| ISSN: | 1539-6304 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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