Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy

作者：Astrid Voskamp, Sugandhika Khosa, T. Phan, Hannah A. DeBerg, Judy M. Bingham, Mark Hew, William Smith, Jodie B. Abramovitch, Jennifer M. Rolland, Matthew Moyle, Kari C. Nadeau, Gideon Lack, Mark Larché, Erik Wambre, Robyn E. O’Hehir, Pascal Hickey, Sara R. Prickett · 发表于：Allergy · 年份：2023 · DOI：10.1111/all.15966 · 被引用次数：26 · 研究领域：Food Allergy and Anaphylaxis Research、Allergic Rhinitis and Sensitization、Transgenic Plants and Applications

Abstract Background Food allergy is a leading cause of anaphylaxis worldwide. Allergen‐specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short‐lived efficacy. Allergen‐derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T‐cell epitopes of major peanut allergens for treatment of peanut allergy. Methods Pre‐clinical safety of PVX108 was assessed using ex vivo basophil activation tests ( n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first‐in‐human, randomized, double‐blind, placebo‐controlled trial in peanut‐allergic adults (46 active, 21 placebo). The repeat‐dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre‐dose, Week 21 and Month 18 after treatment. Results PVX108 induced negligible activation of peanut‐sensitised basophils. PVX108 was safe and well tolerated in peanut‐allergic adults. There were no treatment‐related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2 + Th2A:CCR6 + Th17‐like cells within the peanut‐reactive Th pool which strengthened following treatment. C...