Etanercept for the Treatment of Chronic Urticaria
Information source: University of Utah
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Idiopathic Urticaria
Intervention: etanercept (Drug); placebo (Drug)
Phase: Phase 2/Phase 3
Status: Not yet recruiting
Sponsored by: University of Utah
Official(s) and/or principal investigator(s):
Christopher Hull, MD, Principal Investigator, Affiliation: University of Utah Department of Dermatology
Mark Eliason, MD, Phone: 801-581-6465, Email: email@example.com
The purpose of this study is to evaluate the safety and efficacy of etanercept for patients
with chronic idiopathic urticaria unresponsive to antihistamines.
Official title: A 6 Week Randomized, Double Blind, Placebo-controlled Study With a 6 Week Open Label Extension to Assess the Efficacy of Etanercept in the Treatment of Chronic Idiopathic Urticaria
Study design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: To determine the efficacy of etanercept on the clinical features of CIU. A positive response to treatment (a % change from baseline of urticaria activity scores
Secondary outcome: Study the safety of etanercept in the treatment of CIU
Chronic urticaria is a common condition which can be debilitating, difficult to treat, and
sometimes life-threatening. Approximately 15-25% of the population is affected by urticaria
at least once in their lifetime, and chronic urticaria develops in more than 25% of these
cases. Chronic urticaria is characterized by frequent, often daily, development of pruritic
wheals of 6 weeks duration or longer. The average duration of chronic urticaria is 3-5
years in adults. In the majority of cases, an underlying trigger for the urticaria is not
identified and these cases are referred to as idiopathic (CIU). These considerations have
led to the hypothesis that CIU may have an autoimmune etiology.
CIU is a major affliction causing serious disability to a degree equal to that experienced
by sufferers from coronary artery disease. Antihistamines are the most common therapy used.
However, most cases of CIU are resistant to combinations of antihistamines and other
therapies. In addition, patients are often intolerant to the side effects of antihistamines
including sedation and cognitive dysfunction. The treatment of CIU patients can be
frustrating. For those who do not respond to typical treatments, other therapies are
needed. In many patients, immunosuppressant medications are required but this can lead to
adverse effects such as renal dysfunction, liver function abnormalities, and anemia. A
safer and more efficacious therapy is clearly needed for CIU.
A few preclinical investigations have demonstrated an upregulation of TNF-alpha in patients
with CIU. This is in contrast to acute urticaria where TNF-alpha does not appear to play as
important of a role in the inflammatory response . This may explain why patients with CIU
do not typically respond to usual therapies for acute urticaria. It has been suggested that
CIU is an immediate hypersensitivity phenomenon appearing immediately after exposure to an
antigen, but the presence of a delayed inflammatory phase is nevertheless observed in this
pathology. Soluble factors play a role in this delayed inflammatory phase. Cytokines,
including TNF-alpha, are important mediators the pathogenesis of this delayed response.
Studies have demonstrated a similar immune profile as that found in patients with rheumatoid
arthritis. In one study, cytokines were evaluated in lesional and non-lesional skin of
patients with acute urticaria, CIU, delayed pressure urticaria, and cold urticaria. This
study demonstrated upregulation of TNF-alpha on endothelial cells and perivascular cells in
the dermis. Additionally, TNF-alpha was expressed throughout the epidermis in lesional and
non-lesional skin of CIU patients, but not controls. These preclinical investigations
support the use of targeted therapy of TNF-alpha in patients with CIU. Therapies directed
at modulating the effects of TNF-alpha, including etanercept, may provide effective and safe
long-term treatment for patients not responding to anti-histamines alone.
HYPOTHESIS: We hypothesize that the blockage of TNF with etanercept could be a useful and
safe therapy for patients with CIU.
Primary Objective: To determine the efficacy of etanercept on the clinical features of CIU.
A positive response to treatment (a % change from baseline of urticaria activity scores
Secondary Objective: Study the safety of etanercept in the treatment of CIU
Minimum age: 18 Years.
Maximum age: N/A.
1. History of CIU occurring at least biweekly for greater than 6 week
2. Adult subjects between the ages of 18-70 years
3. Failure to respond to systemic antihistaminic therapy
4. Negative TB skin testing at baseline
5. Subjects willing to comply with study requirements
6. Negative urine pregnancy test at enrollment
7. Voluntarily sign and date informed consent form
1. Current enrollment in any other investigational device or investigational drug
trial(s), or receipt of any other investigational agent(s) within 28 days before
2. Known hypersensitivity to Enbrel® (etanercept) or any of its components or known to
have antibodies to etanercept.
3. Latex sensitivity
4. Prior or concurrent use of cyclophosphamide therapy
5. Concurrent sulfasalazine therapy.
6. Known HIV-positive status or known history of any other immuno-suppressing disease.
7. Any mycobacterial disease or high risk factors for tuberculosis (TB), such as family
member with TB, positive purified protein derivative (PPD) or taking
8. Active or chronic infection within 4 weeks before screening visit, or between the
screening and baseline visits.
9. Severe comorbidities (diabetes mellitus requiring insulin; CHF of any severity or
myocardial infarction or cerebrovascular accident or transient ischemic attack within
3 months of screening visit; unstable angina pectoris, uncontrolled hypertension
(sitting systolic BP <80 mm Hg or > 160 or diastolic BP > 100 mm Hg),
oxygen-dependent severe pulmonary disease, history of cancer within 5 years [other
than resected cutaneous basal or squamous cell carcinoma of the skin or in situ
10. Exposure to hepatitis B or hepatitis C or to high risk factors for hepatitis B or C,
such as intravenous drug use in patient.
11. Systemic lupus erythematosus, history of multiple sclerosis, transverse myelitis,
optic neuritis or seizure disorder.
12. Use of a live vaccine 90 days prior to screening visit, or concurrent use of a live
13. Any condition or circumstances judged by the patient's investigator to render this
clinical trial detrimental or otherwise unsuitable for the patient's participation.
14. History of non-compliance with other therapies.
15. Concurrent use of anakinra.
16. Use of systemic immunosuppressive medication within 2 weeks of enrollment
17. Use of dapsone, sulfapyridine, sulfasalazine, or colchicine within 2 weeks of
18. Use of systemic corticosteroid within 2 weeks of enrollment
19. For females of childbearing potential, a refusal to use an acceptable form of
contraceptive including oral or patch birth control, injectable birth control,
intrauterine device, surgical sterilization, condom, barrier, or spermicide,
post-menopausal, or complete abstinence from sexual activity.
20. For females, pregnancy, breast-feeding, or lactation
21. Active or recent (within the previous month) infection by staphylococcus aureus
Locations and Contacts
Mark Eliason, MD, Phone: 801-581-6465, Email: firstname.lastname@example.org
University of Utah Department of Dermatology, Salt Lake City, Utah 84132, United States
Starting date: January 2010
Last updated: December 10, 2009