Short summary

Full title: A randomized, double-blind, placebo-controlled study to determine the safety, tolerability and immunological effects of BM41 compared to placebo and to treatment with standard subcutaneous immunotherapy (as open comparator) in patients with moderate to severe allergic rhinitis/ rhino-conjunctivitis caused by birch pollen

Birch pollen allergy can negatively affect quality of life. Conventional treatment with antihistamines may not always be sufficient and allergen immunotherapy can in these cases be an alternative, however there is a risk of side effects and lack of efficacy. 

This study is a first-in-human study investigating a immunotherapy treatment for birch pollen allergy, BM41, expected to be safer and more effective.

Rationale

For decades, allergen immunotherapy has been used as a causal therapeutic option in the treatment of IgE-mediated allergic diseases such as allergic rhinitis, allergic rhinoconjunctivitis or allergic asthma. Efficacy of this therapeutic principle is well documented for allergen extract-based products, but the required duration of the treatment of at least three years of monthly injections and the (controlled) risk of severe side-effects are experienced to be significant drawbacks. There is a need for a treatment with a lower risk of side-effects and a more rapid onset of longlasting efficacy, i.e. less injections.  BM41 is a hypoallergenic (safer) but hyper-immunogenic (more effective) recombinant variant of Bet v 1, the major allergen of birch pollen, and is a candidate for such an optimized immunotherapy treatment in terms of safety and efficacy. 

The aim of this clinical phase I/IIa single centre, randomized, double-blind,  placebo-controlled study with open comparator  is to investigate tolerability and safety as well as the immunological effects of BM41 in comparison to placebo (double blind) and to a standard subcutaneous immunotherapy Alutard SQ (open) in birch allergic patients.

A total of 45 birch pollen allergic patients with moderate to severe allergic rhinitis/allergic rhinoconjunctivitis with/without concomitant controlled allergic asthma will be included. Treatment will be performed as a pre-seasonal course of 9 visits during 15 weeks with a total of 9 injections with BM41 or placebo. In parallel, a third group will be treated during 9 visits with a total of 15 injections of a registered product for subcutaneous immunotherapy, Alutard SQ, following a cluster up-dosing scheme.

Description of the cohort

Men and women, 18-65 years of age with moderate to severe birch pollen induced rhinitis/rhinoconjunctivitis 

Data and biological material

Blood samples 

Skin prick test

Lung function 

Urine test

ECG

Clinical data

Collaborating researchers and departments

Odense Research Center for Anaphylaxis (ORCA), Dept. of Dermatology and Allergy Center

• Line K. Tannert, PhD
• Morten Junker Christensen, PhD
• Professor Charlotte G. Mørtz, PhD
• Consultant Henrik Fomsgaard Kjær

Department of Experimental Immunology and Department of Otorhinolaryngology,

• Academic Medical Center, Amsterdam
• Professor Ronald van Ree
• Laurian Jongejan

Department of Biosciences, Division of Allergy and Immunology

Paris Lodron University of Salzburg 

• Dr. Lorenz Aglas