Detailed profiling of chronic inducible urticaria (symptomatic dermographism and cold urticaria)

Inclusion Criteria:

Healthy volunteers

* 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.
* No clinically significant skin disease in the research area
* No history of hypertrophic scarring or keloid.
* Willing to give written informed consent and willing and able to comply with the study protocol.
* Negative TempTest and FricTest at screening.
* 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:

* Male and female subjects aged ≥18 years
* 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).
* 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
* Willing to give written informed consent and willing and able to comply with the study protocol.
* Positive provocation test:

  1. 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;
  2. For SD patients: developing a wheal at the test site within 10 min after using FricTest® with ≥ 3mm at both screening and Baseline.
* For CSU patients: negative TempTest® and FricTest® at screening
* 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.
* Female participants of reproductive potential must agree to use contraception from screening until EOS.

Exclusion Criteria:

* 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.
* History of immunological abnormality (e.g., immune suppression) that may interfere with study objectives, in the opinion of the investigator.
* Loss or donation of blood over 500 mL within three months prior to screening.
* Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody (HCV ab), or human immunodeficiency virus antibody (HIB ab) at screening
* Known infection requiring (topical or oral) antibiotic therapy within 56 days prior to Day 1.
* The use of systemic antibiotic therapy for \>2 months the past 12 months.
* 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.
* Treatment with omalizumab within 5 half lives (120 days) prior to Day 1
* Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding.
* 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.
* Evidence of current drug or alcohol abuse.
* 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)

Healthy volunteers

\- Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year.

Eligible patients

* 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.
* 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).
* Active, pruritic skin condition in addition to CIndU (CIndU patients) or CSU (CSU patients).
* 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.
* Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening.
* Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to Day 1.
* Any H2 antihistamine use within 7 days prior to Day 1.
* Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to Day 1.
* 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 excised and is considered resolved.
* Hypersensitivity to omalizumab or any component of the formulation.
* History of anaphylactic shock.
* Evidence of parasitic infection.