Chronic inducible urticaria, Symptomatic dermographism Urticaria
Conditions
Interventions
Omalizumab
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Healthy volunteers must meet all of the following inclusion criteria: 1. Male and female subjects between 18-69 years of age; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination and vital signs. 2. No clinically significant skin disease in the research area 3. No history of hypertrophic scarring or keloid. 4. Willing to give written informed consent and willing and able to comply with the study protocol. 6. Negative TempTest and FricTest at screening. 7. Participant is willing to refrain from extensively washing (including bathing, swimming, showering and excessive sweating) the skin 12 hours before study visit 1. Eligible patients must meet all of the following inclusion criteria at screening: 8. Male and female subjects aged >18 years 9. Diagnosis of SD, ColdU or CSU (moderate to severe according to international guidelines (Zuberbier et al, 2022)) for >=3 months and symptomatic disease despite treatment with H1 antihistamines (up to fourfold the approved dose). 10. Patients currently on an antihistamine (up to fourfold the approved dose) must be on a stable dose for at least 2 weeks prior to day 1 and must maintain the same stable dose throughout the treatment period. Patients are according to the stepped care model eligible to start treatment with omalizumab. 11. Willing to give written informed consent and willing and able to comply with the study protocol. 12. Positive provocation test: a) For ColdU patients: developing a wheal at the test site within 10 min after using TempTest® at any temperature at both screening and Baseline. Alternatively, patients with a negative TempTest® may also be included if they have a positive ice cube test; b) For SD patients: developing a wheal at the test site within 10 min after using FricTest® with >= 3mm at both screening and Baseline. 13. For CSU patients: negative TempTest® and FricTest® at screening 14. Participant is willing to refrain from extensively washing (including bathing, swimming, showering and excessive sweating) the skin 12 hours prior to Day 1 and EOS. 15. Female participants of reproductive potential must agree to use contraception from screening until EOS.
Exclusion criteria
Exclusion criteria: General for all subjects to be enrolled: 1. Significant, uncontrolled or unstable disease in any organ system as per judgment of the investigator (regardless of association with the immunosuppressing disorder/therapy), including but not limited to: psychiatric, neurologic, cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, hematologic or respiratory disease. 2. History of immunological abnormality (e.g., immune suppression) that may interfere with study objectives, in the opinion of the investigator. 3. Loss or donation of blood over 500 mL within three months prior to screening. 4. Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody (HCV ab), or human immunodeficiency virus antibody (HIB ab) at screening (healthy volunteers only) 5. Known infection requiring (topical or oral) antibiotic therapy within 56 days prior to Day 1. 6. The use of systemic antibiotic therapy for >2 months the past 12 months. 7. The use of any oral/systemic medication (e.g. immunomodulatory, immunosuppressive) within 28 days prior to Day 1, if the investigator judges that it may interfere with the study objectives. 8. Treatment with omalizumab within 5 half lives (120 days) prior to Day 1. 9. Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding. 10. Have any current and/or recurrent clinically significant or subject reported skin condition other than the CIndU/CSU wherefore subject is included in the study. 11. Evidence of current drug or alcohol abuse. 12. History of regular alcohol consumption within 12 months of the trial defined as an average weekly intake of >21 alcoholic drinks/week for men or >14 alcoholic drinks/week for women (i.e., 1 drink is equivalent to 150 mL of wine or 360 mL of beer or 45 mL of hard liquor). Eligible healthy volunteers must not meet the following exclusion criterion at screening: 13. Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year. Eligible patients must meet none of the following exclusion criteria at screening: 14. For CIndu patients: active CSU or other forms of CIndU besides ColdU or SD that may interfere with study assessments. For CSU patients: presence of active CIndU Disease that may interfere with study assessments. 15. Urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency). 16. Active, pruritic skin condition in addition to CIndU (CIndU patients) or CSU (CSU patients). 17. Routine doses of the following medications within 30 days prior to Day 1: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide. 18. Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening. 19. Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to Day 1. 20. Any H2 antihistamine use within 7 days prior to screening. 21. Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to Day 1. 22. Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excise
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints for the primary objectives: • Blood-based biomarkers (including but not limited to abs. eosinophil counts, abs. basophil counts, C-reactive protein, total serum IgE, D-dimer, complement assessement, basophil activation test , IgG-anti-Fc*RI, cytokine profile assessment) • Skin punch biopsies: o Histology o Spatial metabolomics o Tissue CyTOF o Transcriptomics | — |
Secondary
| Measure | Time frame |
|---|---|
| • To evaluate biomarkers for disease-monitoring during standard of care treatment with omalizumab and at follow-up; • To evaluate the response of the biomarkers and disease characteristics to standard of care treatment with omalizumab. • To explore the variability of the selected biomarkers between patients and within patients over time during and in relation to standard of care treatment (omalizumab); • To explore and determine the different endotypes of cold urticaria and symptomatic dermographism. Secondary endpoints: • Provocations test: TempTest®, FricTest® • Swab of healthy skin and (non-) lesional skin for microbiome • Faecal microbiota • Antera 3D multispectral imaging (3D skin morphology, erythema, haemoglobin and melanin levels) • Laser speckle contrast imaging (microcirculation) • 2D photography • ePRO ( Electronic patient reported outcomes): UAS7, UCT, DLQI, SDAS, SD-Qol, Cold-UAS, Coldu-QOL • Withing watch • Skin barrier assessment by Nevisense • Stratum corneum sampling with tape stripping | — |
Countries
Netherlands
Contacts
Public ContactR. Rissmann
Centre for Human Drug Research
Outcome results
None listed