Urticaria Facticia Treatment With Omalizumab (UFO)

Study Overview
=================
Brief Summary
-----------------
Urticaria is a very frequent skin condition characterized by transient wheal and flare type skin reactions associated with severe pruritus. In Europe alone, more than 5 million patients are thought to suffer from persisting urticaria symptoms, which either occur spontaneously, i.e. in chronic spontaneous urticaria (CSU), or as a result of environmental physical stimuli such as friction, pressure, UV irradiation or cold (physical urticaria). Urticaria factitia (also known as dermographic urticaria and symptomatic dermographism) is characterized by whealing and itching following a minor stroking pressure, rubbing or scratching of the skin. The majority of patients with urticaria factitia benefits from treatment with nonsedating antihistamines. Some patients, however, do not achieve adequate symptom control even with updosing of antihistamines and may suffer from substantial quality of life impairment . Since even very minor stroking of the skin can lead to the development of wheals and severe itching, these patients are for example limited in their choice of clothing and are impaired in their social interaction and partnership. In all patients with a history of wheals after stroking of the skin, a provocation test should be performed. This can be done by stroking of the skin lightly with a smooth blunt object (e.g. the tip of a closed ball point pen or a wooden spatula) or a purpose-built instrument, known as a dermographometer. For the diagnosis of symptomatic dermographism, the smooth blunt object should be held perpendicular to the skin and should be used to apply a light stroking pressure to the skin of the upper back or volar forearm. The reaction is considered positive in patients who show a weal response and report pruritus at the site of provocation. Patients with a positive test reaction should be evaluated for individual pressure thresholds. For this purpose a provocation device (FricTest) has been developed that allows for reproducible and standardized threshold testing. Threshold testing enables physicians to assess disease severity and treatment response more precisely.

Official Title
-----------------
Double-blind, Placebo-controlled 12-week, Parallel-group Study With a 6 Weeks Follow up Period to Demonstrate Efficacy and Safety of Subcutaneous Omalizumab in Patients With Urticaria Factitia Refractory to Standard Treatment

Conditions
-----------------
Symptomatic Dermographism

Intervention / Treatment
-----------------
* Drug: Omalizumab
* Drug: Omalizumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (18-75 years) Informed consent signed and dated Able to read, understand and willing to sign the informed consent form and abide with study procedures Diagnosis of UF lasting for at least 6 months Willing, committed and able to return for all clinic visits and complete all study-related procedures, including willingness to have SC injections administered by a qualified person In females of childbearing potential: Negative pregnancy test; females willing to use highly effective contraception (Pearl-Index < 1). A woman will be considered not of childbearing potential if she is post-menopausal for greater than two years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) No participation in other clinical trials 4 weeks before and after participation in this study Exclusion Criteria: Patients with acute urticaria Concurrent/ongoing treatment with immunosuppressives (e.g. systemic steroids, cyclosporine, methotrexate, dapsone or others) within 4 weeks or 5 half lives prior to day 0, whichever is longer Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial Significant concomitant illness that would adversely affect the subject's participation or evaluation in this study History of malignancies within five years prior to screening other than a successfully treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cancer Presence of clinically significant laboratory abnormalities Lactating females or pregnant females Subjects for whom there is concern about compliance with the protocol procedures Any medical condition which, in the opinion of the Investigator, would interfere with participation in the study or place the subject at risk History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) within the last 5 years that could limit the subject's ability to comply with study procedures Subjects who are detained officially or legally to an official institute Previous use of omalizumab within the last 6 months Intake of antihistamines or leukotriene antagonists within 4 days prior to visit 1 Intake of oral corticosteroids within 14 days prior to visit 1 Use of depot corticosteroids or chronic systemic corticosteroids within 21 days before beginning of the study Known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g.: monoclonal antibodies, polyclonal gammaglobulin)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab 150mg<br> | Drug: Omalizumab<br>* 150mg, s.c., every 4 weeks<br>* Other names: Xolair;|
| Experimental: Omalizumab 300mg<br> | Drug: Omalizumab<br>* 300mg, s.c., every 4 weeks<br>* Other names: Xolair;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo, s.c., every 4 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Provocation Thresholds From Baseline to Day 70 in Urticaria Factitia Patients After Treatment With Omalizumab Compared to Placebo | Patients receive provocation test by FricTest (standardized stroking of the skin). FricTest ratings are from 0 (no wheal development to the longest pin) to 4 (wheal development to all four pins). The development of wheals within 30 minutes after provocation is monitored. | 70 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Effects of Omalizumab in Urticaria Factitia Patients on Quality of Life | Change in quality of life scores assessed by Dermatology Life Quality Index (DLQI) and UF specific life quality questions from baseline to day 70 after treatment with omalizumab compared to placebo. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percantage of the maximum possible score of 30. | 70 days | 
| To Assess the Effects of Omalizumab in UF Patients on Number of Symptom Free Days | Change in number of symptom free days as assessed by a patient diary from baseline to day 70 after treatment with omalizumab compared to placebo | 70 days | 
| To Assess the Effects of Omalizumab in UF Patients on Physician Global Assessment of Disease Severity | Change in physician global assessment of disease severity assessed by visual analogue scale by a physician from baseline to day 70 after treatment with omalizumab compared to placebo. VAS are measuring instruments designed to document the characteristics of disease-related symptom severity in individual patients. The scale ranges from a minimum of 0 and a maximum of 10. The higher the score, the worse the outcome. | 70 days | 
| To Assess the Effects of Omalizumab in UF Patients on Patient Global Assessment of Disease Severity | Change in patient global assessment of disease severity assessed by visual analogue scale by the patient from baseline to day 70 after treatment with omalizumab compared to placebo. VAS are measuring instruments designed to document the characteristics of disease-related symptom severity in individual patients. The scale ranges from a minimum of 0 and a maximum of 10. The higher the score, the worse the outcome. | 70 days | 
| To Assess Long-term Effects of Omalizumab in UF Patients | To assess long-term effects of omalizumab in UF patients, change in friction thresholds from day 70 (week 10) to day 112 (week 16) will be assessed | 112 days | 
| Number of Participants With Serious Adverse Events and Adverse Events | Safety of patients treated with omalizumab: This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting | 112 days |