Allergen exposure chambers: implementation in clinical trials in allergen immunotherapy

Abstract

Allergen exposure chambers (AECs) have been developed for controlled allergen challenges of allergic patients mimicking natural exposure. As such, these facilities have been utilized e.g., for proof of concept, dose finding or the demonstration of onset of action and treatment effect sizes of antiallergic medication. Moreover, clinical effects of and immunological mechanisms in allergen immunotherapy (AIT) have been investigated in AECs. In Europe AIT products have to fulfill regulatory requirements for obtaining market authorization through Phase I to III clinical trials. Multiple Phase II (dose-range-finding or proof-of-concept) trials on AIT products have been performed in AECs. However, they are not accepted by regulatory bodies for pivotal (Phase III) trials and a more thorough technical and clinical validation is requested. Recently, a Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI) has outlined unmet needs in further development of AECs. The following review aims to address some of these needs on the basis of recently published data in the first part, whereas the second part overviews published examples of most relevant Phase II trials in AIT performed in AEC facilities.

Total IgE in tears accurately reflects the severity and predicts the prognosis of seasonal allergic conjunctivitis

“…The diagnosis of ocular allergies is primarily clinical, although laboratory tests can be useful in supporting the diagnosis 6 . At present, laboratory tests for AC mainly include cytological examination, skin prick tests, and total IgE antibody detection 15–17 . The detection of eosinophils is a complex procedure with a low detection rate of approximately 60% in conjunctival scrapings from patients with mild allergic conditions 18 .…”

“…6 At present, laboratory tests for AC mainly include cytological examination, skin prick tests, and total IgE antibody detection. 15 , 16 , 17 The detection of eosinophils is a complex procedure with a low detection rate of approximately 60% in conjunctival scrapings from patients with mild allergic conditions. 18 Skin prick tests are invasive and require multiple pricks with small volumes of allergens.…”

Targeted micronutrition via holo-BLG based on the farm effect in house dust mite allergic rhinoconjunctivitis patients – first evaluation in a standardized allergen exposure chamber

“…V0 Screening and patient selection, V1 and V3 HDM exposure in AEC, V2 and V4 safety calls junctivitis (ARC). A standardized and reproducible exposure of HDM allergic patients with HDM material was performed in an allergen exposure chamber (AEC), a highly standardised platform that reliably and reproducibly generates allergic symptoms [24][25][26][27][28]. Therefore, an AEC is an excellent choice for the first evaluation of this novel FSMP in HDM-induced ARC, designed to investigate the effects of the daily intake of holo-BLG for 3 months by a controlled challenge.…”

Update on the use of allergen challenge chambers in immunotherapy: clinical implications

“…Along with this, studies are planned involving several AECs in a multicenter approach to document inter-chamber variability of clinical outcomes and demonstrate correlation of results as discussed above [25,26]. Also, further activity will be posed on a consensus for hybrid design models of AIT clinical development programs in AEC models as requested by regulatory authorities [27].…”