An exploratory, multi-centre, two-part study to describe chronic induced urticaria characteristics and explore novel biomarkers with a multimodal patient profiling approach by comparing CIndU patients to chronic spontaneous urticaria patients and healthy volunteers

• Conditions: Chronic inducible urticaria; Symptomatic dermographism; 10002426

• Registration Number: NL-OMON56483
• Lead Sponsor: Centre for Human Drug Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 40

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.
5. Body mass index (BMI) > 18.0 and < 35 kg/m2.
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 between 18-69 years old
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. Body mass index (BMI) > 18.0 and < 35.0 kg/m2.
12. Willing to give written informed consent and willing and able to comply
with the study protocol.
13. 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;
b) For SD patients: developing a wheal at the test site within 10 min after
using FricTest® with >= 3mm at both screening and Baseline.
14. For CSU patients: negative TempTest® and FricTest® at screening
15. 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.
16. Female participants of reproductive potential must agree to use
contraception from screening until EOS.

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 sus

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoints for the primary objectives:<br /><br><br /><br>• Blood-based biomarkers (including but not limited to abs. eosinophil counts,<br /><br>abs. basophil counts, C-reactive protein, total serum IgE, D-dimer, complement<br /><br>assessement, basophil activation test , IgG-anti-Fc*RI, cytokine profile<br /><br>assessment)<br /><br>• Skin punch biopsies:<br /><br>o Histology<br /><br>o Spatial metabolomics<br /><br>o Tissue CyTOF<br /><br>o Transcriptomics</p><br>