Cold Urticaria Treatment With Xolair (CUTEX)

A Two-center, Double Blind, Placebo-controlled Study in Parallel Design to Assess the Efficacy and Safety of 150 and 300 mg Omalizumab in Subjects With Antihistamine-resistant Cold Contact Urticaria (CCU)

Urticaria is a very frequent skin condition characterised by transient wheal and flare type skin reactions associated with severe pruritus. Cold contact urticaria (CCU) is a frequent form of physical urticaria that is characterized by the development of wheal and flare type skin reactions due to the release of histamine and other proinflammatory mast cell mediators following exposure of the skin to cold. Among all physical urticaria subtypes the frequency of CCU varies between 5.7% and 33.8% in different studies. Physical urticarias including CCU are known to severely impair the quality of life of affected patients.

The treatment of choice in CCU, as well as in other inducible forms and spontaneous urticaria, are non-sedating H1 antihistamines. Recent data have shown that updosing of H1 blockers is significantly more effective in reducing symptoms in cold urticaria than standard-dose treatment. Thus, patients who cannot be sufficiently controlled with standard-dose antihistamines should receive high-dose H1 blockers up to 4 times the standard dose as recommended by the new international guidelines for the management of urticaria.

Previous phase II studies in patients with chronic spontaneous urticaria have shown favorable results for the treatment with omalizumab (Xolair®). Proof-of-concept data from completed studies suggest that omalizumab improves urticaria in patients with chronic spontaneous urticaria who have failed treatment with H1 antihistamines as well as those who have failed treatment with a combination of H1 and H2 antihistamines and a leukotriene receptor antagonist. In addition, two case reports of patients with severe therapy refractory CCU treated with omalizumab reported a complete response with no urticarial symptoms after cold challenge. In summary, these data suggest that omalizumab may have a beneficial effect in the treatment of CCU.

Study Overview

• Status: Completed
• Conditions: Cold Contact Urticaria
• Intervention / Treatment: Drug: Omalizumab; Drug: Omalizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • University Aachen
  • Berlin, Germany, 10117
    • Allergie-Centrum-Charité, Charité - Universitätsmedizin Berlin
  • Mainz, Germany
    • Hautklinik Mainz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adults (18 years or older) Informed consent signed and dated Able to read, understand and willing to sign the informed consent form and abide with study procedures Diagnosis of CCU 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 7 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo, s.c., every 4 weeks
EXPERIMENTAL: Omalizumab 150mg	Drug: Omalizumab; 150mg, s.c., every 4 weeks; Other Names: Xolair; Drug: Omalizumab; 300mg, s.c., every 4 weeks; Other Names: Xolair
EXPERIMENTAL: Omalizumab 300mg	Drug: Omalizumab; 150mg, s.c., every 4 weeks; Other Names: Xolair; Drug: Omalizumab; 300mg, s.c., every 4 weeks; Other Names: Xolair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Critical Temperature Thresholds (CTT) From Baseline to Day 70 After Treatment With Omalizumab Compared to Placebo	The primary efficacy outcome was the change in trigger thresholds from baseline to week ten using TempTest® to assess critical temperature thresholds in °C.	day 70

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Abnormal Physical Examinations, Laboratory Assessments, Vital Signs, and Adverse Events	This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting	day 70

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Martin Metz, MD, Charité

Publications and helpful links

General Publications

• Metz M, Schutz A, Weller K, Gorczyza M, Zimmer S, Staubach P, Merk HF, Maurer M. Omalizumab is effective in cold urticaria-results of a randomized placebo-controlled trial. J Allergy Clin Immunol. 2017 Sep;140(3):864-867.e5. doi: 10.1016/j.jaci.2017.01.043. Epub 2017 Apr 4. No abstract available.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: April 18, 2012
• First Submitted That Met QC Criteria: April 18, 2012
• First Posted (ESTIMATE): April 19, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2017
• Last Update Submitted That Met QC Criteria: February 23, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Physiological Effects of Drugs; Immunologic Factors; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Antibodies, Monoclonal; Omalizumab
• Other Study ID Numbers: CIGE025EDE14T