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Original Article

 

Tolerability During Double-Blind Randomized Phase I Trials With the House Dust Mite Allergy Immunotherapy Tablet in Adults and Children

 

JL Corzo,1 T Carrillo,2 C Pedemonte,3 AM Plaza Martín,4 S Martin Hurtado,5 E Dige,6 MA Calderon7

1Hospital Materno Infantil, Malaga, Spain
2Hospital Dr. Negrín, Las Palmas, Spain
3Hospital de Nens, Barcelona, Spain
4Hospital Sant Joan de Deu, Barcelona, Spain
5Medical Department, ALK, Madrid, Spain
6Global Clinical Development, ALK, Hørsholm, Denmark
7Imperial College London, NHLI, Royal Brompton Hospital, London, UK

J Investig Allergol Clin Immunol 2014; Vol. 24(3): 154-161

 

 Abstract


Background and Objective: The orodispersible house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) is being developed for the treatment of HDM respiratory allergic disease. The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease.

Patients and Methods: The trials were randomized, multiple-dose, dose-escalation, double-blind, placebo-controlled phase I trials including patients with HDM-induced asthma, with or without rhinoconjunctivitis. Both trials were registered in EudraCT (Trial 1: 2005-002151-41; Trial 2: 2007-000402-67). Trial 1 included 71 adults (18-63 years) and trial 2 included 72 children (5-14 years). Both trials included 6 dose groups that were randomized 3:1 to active treatment or placebo once daily for 28 days. Adverse events (AEs) were coded in MedDRA (version 8.1 or later). Immunological variables included specific IgE and IgE-blocking factor.

Results: No serious AEs were reported. In trial 1 (maximum dose, 32 development units [DU]), 1 patient in the 16 DU group discontinued due to AEs. The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction. In trial 2 (maximum dose, 12 DU), no patients discontinued prematurely. The most frequently reported AEs were mild application-site related events. The total number of events was dose-related within each trial. HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner.

Conclusions: These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected populations, and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease.

Key words: Sublingual immunotherapy tablet. House dust mite. Placebo-controlled. Sublingual Immunotherapy. Phase I.