The purpose of this study is to assess the efficacy in reducing disease activity and safety of Dupilumab in adult patients with chronic spontaneous urticaria (CSU) who are symptomatic despite H1-antihistamine treatment.
Treatment with Dupilumab has been shown to reduce clinically significant exacerbations and to improve skin symptom control as well as quality of life in moderate to severe atopic dermatitis patients and in moderate to severe asthma patients. It has been approval by European Medicines Agency (EMA) for the treatment of atopic dermatitis patients in September 2017. Dupilumab is a novel monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in atopic dermatitis and asthma. Considering that CSU and atopic diseases share many common features (e.g. key pathogenic role of mast cells and immunoglobulin E (IgE), itch is a dominant symptom, Th2 dominance), it is reasonable to expect that Dupilumab is beneficial in CSU. These results suggest that Dupilumab may provide an effective treatment option for patients with insufficient treatment responses to H1-antihistamines exhibiting wheal and flare type skin reactions. The gold standard treatment of CSU consists of administration of antihistamines. In more than 50% of the patients, symptoms persist with standard dosing of antihistamines. In antihistamine-refractory patients with chronic spontaneous urticaria, the currently only licensed treatment is omalizumab, a monoclonal anti-IgE antibody. In 2014, omalizumab has been licensed for add-on therapy in CSU patients who still have symptoms despite standard-dosed antihistamine treatment. There is, however, still a great medical need for additional treatment options, as 20-40% of patients are still without effective therapy. These patients have no other licensed treatment option and can only be treated off-label with therapeutics with several known safety risks such as Cyclosporine A. Dupilumab has excellent potential to provide symptom control in CSU. This study will provide additional valuable insights into the therapeutic potential of Dupilumab in improving quality of life in these patients, in addition to managing CSU symptoms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
Universitätsklinikum Giessen und Marburg
Marburg, Hesse, Germany
Hautklinik Universitätsklinikum Münster
Münster, NRW, Germany, Germany
Hautklinik der Universitätsmedizin Mainz Clinical Research Center
Mainz, Rheinland-Pfalz, Germany, Germany
Universitätsklinikum Carl Gustav Carus
Dresden, Saxony, Germany
Urticaria activity score over 7 days (UAS7)
0-42 Points total range over 7 days, higher values equal more disease activity
Time frame: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)
Itch severity score (ISS7; 0 - no pruritus; 21 - most severe pruritus), hive severity score (HSS7; 0 - no hives; 21 - max. hive severity)
Disease activity scores
Time frame: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)
Global assessment for disease activity
Global assessment for disease activity(physician and patient) by visual analogue scale (VAS; 0 - no pain; 10 - max. amount of pain)
Time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
urticaria control test (UCT; 16 - complete disease control; 0 - strong symptoms), dermatological quality of life (DLQI; 0 - no impairment; 30 - max. impairment), chronic urticaria quality of life (Cu2-QoL; 23 - no impairment; 115 - max. impairment)
Disease specific quality of life
Time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
Responder rates (regarding disease activity and quality of live (QoL))
Responder rates (regarding disease activity and quality of live (QoL))
Time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
rate of angioedema burdened days angioedema activity score (AAS; 0 - lowest disease activity; 15 - highest disease activity) angioedema quality of life (AE-Qol; 0 - no impairment; 100 - worst impairment)
For patients with concomitant angioedema
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Universitätsmedizin Leipzig, Klinik für Dermatologie, Venerologie und Allergologie
Leipzig, Saxony, Germany
Charite University, Berlin, Germany
Berlin, Germany
Time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]
Rescue medication use
Frequency of of how often rescue medication is used
Time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]