Etanercept for the Treatment of Chronic Urticaria (EtanerceptCIU)

May 29, 2015 updated by: University of Utah

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

The purpose of this study is to evaluate the safety and efficacy of etanercept for patients with chronic idiopathic urticaria unresponsive to antihistamines.

Study Overview

Status

Withdrawn

Intervention / Treatment

Detailed Description

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.

OBJECTIVES:

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

Study Type

Interventional

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Department of Dermatology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  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

Exclusion Criteria:

  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 baseline visit.
  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 anti-tuberculosis medication
  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 cervical cancer])
  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 vaccine..
  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 enrollment
  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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: etanercept
etanercept 50mg BIW
etanercept 50mg BIW S.Q.
Other Names:
  • enbrel
Placebo Comparator: placebo
matching placebo
placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Study the safety of etanercept in the treatment of CIU
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Christopher Hull, MD, University of Utah Department of Dermatology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (Anticipated)

July 1, 2012

Study Completion (Anticipated)

October 1, 2012

Study Registration Dates

First Submitted

December 9, 2009

First Submitted That Met QC Criteria

December 10, 2009

First Posted (Estimate)

December 11, 2009

Study Record Updates

Last Update Posted (Estimate)

June 2, 2015

Last Update Submitted That Met QC Criteria

May 29, 2015

Last Verified

May 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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