Urticaria Facticia Treatment With Omalizumab (UFO)

• Sponsor: Charite University, Berlin, Germany (Other)
• Overall Status: Completed
• CT.gov ID: NCT02169115
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 61
• Locations: 2
• Arms: 3
• Duration (Months): 24
• Patients Per Site: 30.5
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Symptomatic Dermographism	Drug: Omalizumab; Drug: Omalizumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omalizumab 150mg	Drug: Omalizumab; 150mg, s.c., every 4 weeks; Other Names: Xolair
Experimental: Omalizumab 300mg	Drug: Omalizumab; 300mg, s.c., every 4 weeks; Other Names: Xolair
Placebo Comparator: Placebo	Drug: Placebo; Placebo, s.c., every 4 weeks

Outcome Measures

Primary Outcome Measures

1. Change in Provocation Thresholds From Baseline to Day 70 in Urticaria Factitia Patients After Treatment With Omalizumab Compared to Placebo [70 days]

   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.

Secondary Outcome Measures

1. To Assess the Effects of Omalizumab in Urticaria Factitia Patients on Quality of Life [70 days]

   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.

2. To Assess the Effects of Omalizumab in UF Patients on Number of Symptom Free Days [70 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

3. To Assess the Effects of Omalizumab in UF Patients on Physician Global Assessment of Disease Severity [70 days]

   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.

4. To Assess the Effects of Omalizumab in UF Patients on Patient Global Assessment of Disease Severity [70 days]

   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.

5. To Assess Long-term Effects of Omalizumab in UF Patients [112 days]

   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

6. Number of Participants With Serious Adverse Events and Adverse Events [112 days]

   Safety of patients treated with omalizumab: This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Dermatology Freiburg	Freiburg		Germany	79104
2	Dermatology University Mainz	Mainz		Germany	55131

Sponsors and Collaborators

• Charite University, Berlin, Germany
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Martin Metz, MD, Charité University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Martin Metz, Professor, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT02169115
• Other Study ID Numbers: CIGE025EDE17T; 2011-005615-87
• First Posted: Jun 20, 2014
• Last Update Posted: Nov 3, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Urticaria; Omalizumab; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks
Period Title: Overall Study
STARTED	19	21	21
COMPLETED	19	21	21
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo	Total
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks	Total of all reporting groups
Overall Participants	19	21	21	61
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	19 100%	21 100%	21 100%	61 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	13 68.4%	9 42.9%	12 57.1%	34 55.7%
Male	6 31.6%	12 57.1%	9 42.9%	27 44.3%
Region of Enrollment (participants) [Number]
Germany	19 100%	21 100%	21 100%	61 100%

Outcome Measures

1. Primary Outcome

Title	Change in Provocation Thresholds From Baseline to Day 70 in Urticaria Factitia Patients After Treatment With Omalizumab Compared to Placebo
Description	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.
Time Frame	70 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks
Measure Participants	19	21	21
Mean (Standard Deviation) [wheal development up to four pins]	-1.8 (1.7)	-2.0 (1.8)	-0.6 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.7
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.8
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.4
	Estimation Comments

2. Secondary Outcome

Title	To Assess the Effects of Omalizumab in Urticaria Factitia Patients on Quality of Life
Description	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.
Time Frame	70 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: s.c., every 4 weeks
Measure Participants	19	21	21
Mean (Standard Error) [Dermatology quality of life score]	-6.611 (1.234)	-5.579 (1.478)	-2.316 (0.949)

3. Secondary Outcome

Title	To Assess the Effects of Omalizumab in UF Patients on Number of Symptom Free Days
Description	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
Time Frame	70 days

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: s.c., every 4 weeks
Measure Participants	0	0	0

4. Secondary Outcome

Title	To Assess the Effects of Omalizumab in UF Patients on Physician Global Assessment of Disease Severity
Description	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.
Time Frame	70 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks
Measure Participants	18	19	20
Mean (Standard Error) [units on a sclae]	21.8 (3.63)	28.33 (6.23)	40.32 (6.162)

5. Secondary Outcome

Title	To Assess the Effects of Omalizumab in UF Patients on Patient Global Assessment of Disease Severity
Description	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.
Time Frame	70 days

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks
Measure Participants	0	0	0

6. Secondary Outcome

Title	To Assess Long-term Effects of Omalizumab in UF Patients
Description	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
Time Frame	112 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks
Measure Participants	18	19	18
Mean (Standard Deviation) [Fric Test grades]	-1.0556 (1.39209)	-0.8421 (1.77210)	-0.8333 (1.50489)

7. Secondary Outcome

Title	Number of Participants With Serious Adverse Events and Adverse Events
Description	Safety of patients treated with omalizumab: This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting
Time Frame	112 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omalizumab 150mg	Omalizumab 300mg	Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks	Omalizumab: 300mg, s.c., every 4 weeks	Placebo: Placebo, s.c., every 4 weeks
Measure Participants	19	21	21
Patients with serious adverse events	1 5.3%	1 4.8%	1 4.8%
Patients with adverse events	17 89.5%	17 81%	19 90.5%

Adverse Events

Arm/Group Title	Omalizumab 150mg		Omalizumab 300mg		Placebo
Arm/Group Description	Omalizumab: 150mg, s.c., every 4 weeks		Omalizumab: 300mg, s.c., every 4 weeks		Placebo: Placebo, s.c., every 4 weeks
All Cause Mortality
	Omalizumab 150mg		Omalizumab 300mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Omalizumab 150mg		Omalizumab 300mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		1/21 (4.8%)		1/21 (4.8%)
Renal and urinary disorders
Unspecified renal colic	0/19 (0%)		0/21 (0%)		1/21 (4.8%)
Acute cystitis	0/19 (0%)		1/21 (4.8%)		0/21 (0%)
Surgical and medical procedures
inguinal hernia	1/19 (5.3%)		0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Omalizumab 150mg		Omalizumab 300mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)		15/21 (71.4%)		18/21 (85.7%)
General disorders
Headache	6/19 (31.6%)		9/21 (42.9%)		10/21 (47.6%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract	12/19 (63.2%)		6/21 (28.6%)		8/21 (38.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.